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Selumetinib – Shrinks Tumors, Provides Clinical Benefit NF1

Selumetinib/Findings from a phase 2 clinical trial show that the drug selumetinib improves outcomes for children with the genetic disorder neurofibromatosis type 1 (NF1). In the trial, selumetinib shrank the inoperable tumors that develop with NF1 called plexiform neurofibromas, and children experienced reduced pain, improved function, and better overall quality of life after receiving the treatment.

The trial was led by intramural researchers in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), part of the National Institutes of Health. Results of the trial were published March 18, 2020, in the New England Journal of Medicine.

“Until now, no effective medical therapies have existed for children with NF1 and plexiform neurofibromas, and it’s been a long journey to find a drug that can help them,” said Brigitte Widemann, M.D., lead author of the study, and chief of CCR’s Pediatric Oncology Branch, which developed and coordinated the trial. “While this is not yet a cure, this treatment is shrinking tumors and it’s making children feel better and have a better quality of life.”

The trial was sponsored by the NCI Cancer Therapy Evaluation Program (CTEP) and conducted by the NIH intramural program. Drugmaker AstraZeneca provided the study drug under a Cooperative Research and Development Agreement with NCI and supported correlated studies that were part of the trial. The company worked closely with the researchers on the New Drug Application to gather the data that has been submitted by the company to the U.S. Food and Drug Administration (FDA). In addition, the Neurofibromatosis Therapeutic Acceleration Program (NTAP) provided funding to support patient enrollment at participating sites.

The trial enrolled 50 children ages 3 to 17 years with NF1-related plexiform neurofibromas in 2015 and 2016. The most common symptoms from the tumors were disfigurement, limitations on strength and range of motion, and pain. The children received selumetinib orally twice a day in 28-day cycles continuously, and assessments were performed at least every four cycles. The researchers used a novel approach to assess outcomes tailored to each patient’s specific tumor-related symptoms, something no prior clinical trial directed at NF1 neurofibromas had done before.

Dr. Brigitte Widemann with Travis Carpenter, who received selumetinib for NF1 at NIH.

As of March 2019, 35 children, or 70%, had a confirmed partial response (≥ 20% volumetric tumor shrinkage), and most of them maintained that response for more than a year. After a year on the treatment, children and parents reported lower levels of pain and clinically meaningful improvement in interference of pain in daily function, overall quality of life, strength, and range of motion.

“One of the most surprising findings of this trial was the impact the treatment had on pain,” said Andrea M. Gross, M.D., of CCR, first author of the study. “It even helped patients who had been living with chronic, debilitating pain come off pain medications, which was not something we anticipated. So that was a really exciting finding.”

Five children stopped receiving selumetinib because of side effects possibly related to the drug, and six children had disease progression. The most frequent side effects included nausea and vomiting, diarrhea, and rashes.

The new study confirmed results of an earlier phase 1 trial that demonstrated for the first time that the drug could shrink large tumors. Dr. Widemann and her team have been studying selumetinib for NF1 since 2011. The drug works by blocking a protein called MEK that is part of the RAS signaling pathway, which is overly active in patients with NF1, leading to the growth of tumors. FDA granted orphan drug designation to selumetinib for the treatment of NF1 in 2018, and in 2019, the drug received FDA breakthrough therapy designation.

Plexiform neurofibromas have proven hard to treat. The tumors can grow quickly and become very large—up to 20% of a child’s body weight. Surgery to remove the tumors is often not feasible because the tumors can be intertwined with healthy nerves and tissue. Tumors that have been partially removed by surgery also tend to grow back, especially in young children.

Dr. Widemann had been doing trials with different medications for NF1 since 2001 and was excited when she saw the first tumors shrink. She and her team are grateful to the many different groups and programs that have worked together to reach this point, including the NCI intramural and extramural programs, NTAP, and the Children’s Tumor Foundation, all of which she said made this work possible. Most of all, however, the researchers want to thank the children and families who participated in the trial.

“There’s a lot more to be done. Even though these children have tumor shrinkage, many still have disabling tumors,” Dr. Widemann said. “But these findings are a big step forward and inspire us to work even harder towards additional progress in NF1 therapies.”

The trial was conducted at the NIH Clinical Center in Bethesda, Maryland, as well as three participating sites: Children’s Hospital of Philadelphia, Cincinnati Children’s Hospital Medical Center, and Children’s National Hospital in Washington, D.C. Both the Children’s Hospital of Philadelphia and Cincinnati Children’s Hospital received additional funding for the trial from NTAP.

About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s contact center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Arenaviruses – Causes, Symptoms, Treatment, Risks

Arenaviruses are enveloped viruses (about 120 nm diameter) with a bi-segmented negative-strand RNA genome. The typical image in electronic microscopy showing grainy ribosomal particles (“arena” in Latin) inside the virions gave the name to this family of viruses.

In 1933, the first virus of the Arenaviridae family, the Lymphocytic Choriomeningitis (LCM) virus, was isolated in North America from a human with aseptic meningitis. Other viruses causing hemorrhagic fevers were reported in South America: Machupo in 1956 in the Beni province of Bolivia, Junín in north Argentina, Guanarito in Portuguesa state in Venezuela in 1989, Sabia in Brazil in 1990 and more recently Chapare in 2004 in Bolivia. Lassa fever was identified in Nigeria in 1969.

Distribution

Cases caused by LCM occur worldwide. Thousands of cases of Lassa fever occur each year in Sierra Leone, Liberia, Guinea and Nigeria. However, limited data is available to assess the real incidence of Lassa fever in West Africa. In Southern America, Junín, Machupo, Guanarito, and Sabia viruses cause sporadic cases or limited outbreaks.

Clinical symptoms of diseases caused by arenaviruses

Arenaviruses cause diseases with two types of clinical presentations: neurological and hemorrhagic fever. However, asymptomatic arenavirus infections may occur.

Neurological – aseptic meningitis, encephalitis or meningoencephalitis, caused by the LCM virus. Overall case fatality is <1%. Fetal infections can result in congenital abnormalities or death. Immunosuppressed patients, such as organ transplant recipients, can develop the fatal hemorrhagic fever-like disease. Transmission of LCMV and an LCMV-like arenavirus via organ transplantation has been documented.

Viral hemorrhagic fever – Lassa fever usually presents as a nonspecific illness: fever, headache, dizziness, asthenia, sore throat, pharyngitis, cough, retrosternal and abdominal pain, and vomiting. In severe forms, facial edema is associated with hemorrhagic conjunctivitis, moderate bleedings (nose, gums, vagina…), and exanthema. Neurological signs may develop and progress to confusion, convulsion, coma and death. Severe prognosis is associated with a high viremia, a serum AST level >150 IU/L (aspartate aminotransferase), bleedings, encephalitis, and edema. There is a very high risk of fetal mortality in pregnant women during the third trimester of pregnancy. Case fatality rates range from 5 to 20% for hospitalized cases.

Clinical symptoms of infection by other arenaviruses in South America are similar to those described for Lassa. Case fatality rates may be higher, up to 30% for the Guanarito virus, although the available epidemiological data is very limited.

Treatment

Ribavirin treatment has been shown to be efficient for Lassa fever. It is more effective when started within the first 6 days of illness. It is presently contraindicated in pregnancy, although it may be warranted if the mother’s life is at risk.

Incubation period

The incubation period is about 10 days (3-21 days).

Vaccine

There is currently no vaccine for Lassa fever but several candidates are under development studies with successful trials in primates. One available vaccine is licensed in Argentina for Junín virus.

Reservoir of Arenavirus

Mastomys natalensis (a peridomestic rodent) is the reservoir of Lassa virus. Its geographic distribution is much wider in sub-Saharan Africa that the presently known area of Lassa transmission. The reported incidence of human Lassa fever cases in West African countries is increased during the dry season.

In the New world, Machupo was identified in wild rodent Calomys callosus in Bolivia, Junín from Calomys musculinus and C. laucha in Argentina , Guanarito from a cotton rat (Sigmodon alstoni) in Venezuela. Many other arenaviruses had been identified in the New World including North America (Whitewater Arroyo, Tamiami…) without any link with a recognized disease in humans.

The identification in 2008 of a new arenavirus, Chapare, from a fatal case in Bolivia showed the importance of fully investigating suspect cases of hemorrhagic fever.

Other arenaviruses had been isolated in Africa from rodents without evidence of disease in humans (Mopeia in Mozambique from the same rodent species Mastomys natalensis, Mobile in the Central African Republic, Kodoko in Guinea from a shrew… ).

Transmission

Arenaviruses are associated with rodents, their natural hosts. Some of these viruses can be transmitted to humans by contact with feces/urine from infected rodents or with dust containing infective particles.

They may cause severe diseases with potential risks of human-to-human transmission via body fluids or droplets. Fatal nosocomial and laboratory infections by arenaviruses have been frequently reported. Contamination occurs via direct contact with body fluids or via droplets. Specific procedures were taken from the 1970s for handling these viruses (now categorized as class 4 agents), including the building of dedicated biosafety laboratories (BSL-4), with containment equipment for all activities involving the virus, infectious or potentially infectious body fluids or tissues

References

  1. https://www.ecdc.europa.eu/en/arenavirus-infection/facts

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Latest Update of Coronavirus – Symptoms and Risks

Latest Update of Coronavirus/Coronavirus (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). A novel coronavirus (nCoV) is a new strain that has not been previously identified in humans.

Coronaviruses are zoonotic, meaning they are transmitted between animals and people.  Detailed investigations found that SARS-CoV was transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans. Several known coronaviruses are circulating in animals that have not yet infected humans.

Common signs of infection include respiratory symptoms, fever, cough, shortness of breath and breathing difficulties. In more severe cases, the infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death.

Standard recommendations to prevent infection spread include regular hand washing, covering mouth and nose when coughing and sneezing, thoroughly cooking meat and eggs. Avoid close contact with anyone showing symptoms of respiratory illness such as coughing and sneezing.

In one of the first reports on the disease, Huang et al. illustrated that patients suffered from fever, malaise, dry cough, and dyspnea.

Countries around the world are stepping up efforts to tackle the new coronavirus that has killed thousands.

As the world further shuts down in the wake of the coronavirus pandemic, more cases are now being recorded outside of China, where the virus was first detected in the central city of Wuhan, than outside.

As of March 19, at least 8,648 people worldwide have died of COVID-19, the disease caused by the coronavirus. More than 207,000 people have tested positive for COVID-19.

What is coronavirus?

According to the WHO, coronaviruses are a family of viruses that cause illnesses ranging from the common cold to more severe diseases such as severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS).

These viruses were originally transmitted from animals to people. SARS, for instance, was transmitted from civet cats to humans while MERS moved to humans from a type of camel.

Several known coronaviruses are circulating in animals that have not yet infected humans.

The name coronavirus comes from the Latin word corona, meaning crown or halo. Under an electron microscope, the looks like it is surrounded by a solar corona.

The novel coronavirus, identified by Chinese authorities on January 7 and since named SARS-CoV-2, is a new strain that had not been previously identified in humans. Little is known about it, although human-to-human transmission has been confirmed.

What are the symptoms?

Latest Update of Coronavirus

According to the WHO, signs of infection include fever, cough, shortness of breath and breathing difficulties.

In more severe cases, it can lead to pneumonia, multiple organ failure, and even death.

Current estimates of the incubation period – the time between infection and the onset of symptoms – range from one to 14 days. Most infected people show symptoms within five to six days.

However, infected patients can also be asymptomatic, meaning they do not display any symptoms despite having the virus in their systems.

Read more on what the coronavirus does to your body if you catch it here.

Latest Update of Coronavirus

How deadly is it?

With more than 8,600 recorded deaths, the number of fatalities from this new coronavirus has surpassed the toll of the 2002-2003 SARS outbreak, which also originated in China.

SARS killed about 9 percent of those it infected – nearly 800 people worldwide and more than 300 in China alone. MERS, which did not spread as widely, was more deadly, killing one-third of those infected.

While the new coronavirus is more widespread than SARS in terms of case numbers, the mortality rate remains considerably lower at approximately 3.4 percent, according to the WHO.

Where have cases been reported?

Since March 16, more cases were registered outside mainland China than inside, marking a new milestone in the spread of the global pandemic.

Deaths have been reported in several countries, with Bahrain recording the first fatality in the Gulf on Monday.

The virus has spread from China all around the world, prompting the WHO to designate the COVID-19 outbreak as a pandemic

Human-to-human transmissions became evident after cases were recorded with no apparent link to China.

Read about which countries have confirmed cases here.

What is being done to stop it from spreading?

Scientists around the globe are racing to develop a vaccine but have warned it is not likely one will be available for mass distribution before 2021.

Meanwhile, Chinese authorities have effectively sealed off Wuhan and placed restrictions on travel to and from several other cities, affecting some 60 million people. Other countries have since followed suit with total lockdowns, closing schools, restaurants, bars, and sports clubs, and also issuing mandatory work-from-home decrees.

International airlines have canceled flights the world over. Some countries have banned non-citizens from entering their territories, and several more have evacuated their citizens from abroad.

Where did the virus originate?

Chinese health authorities are still trying to determine the origin of the virus, which they say likely came from a seafood market in Wuhan, China where wildlife was also traded illegally.

On February 7, Chinese researchers said the virus could have spread from an infected animal species to humans through illegally-trafficked pangolins, which are prized in Asia for food and medicine.

Scientists have pointed to either bats or snakes as possible sources of the virus.

Is this a global emergency?

Yes, this outbreak is a global health emergency, the WHO said on January 30, raising the alarm further on March 11 when it declared the crisis a pandemic.

The international health alert is a call to countries around the world to coordinate their response under the guidance of the WHO.

There have been five global health emergencies since 2005 when the declaration was formalized swine flu in 2009, polio in 2014, Ebola in 2014, Zika in 2016 and Ebola again in 2019.

Latest Update of Coronavirus

Coronavirus live updates: Italy overtakes China’s death toll

Italy’s death toll from coronavirus pandemic rose to 3,405 overtaking a total number of deaths so far registered in China

The death toll from an outbreak of coronavirus in Italy rose in the last 24 hours by 427 to 3,405, overtaking the total number of deaths so far registered in China, officials said on Thursday.

Thursday’s figure represented a slight improvement on the day before, when Italy recorded 475 deaths from COVID-19, while the world has stepped up efforts against the coronavirus pandemic by closing schools, shutting down cities and imposing strict border controls.

Nearly 220,000 people have now been confirmed with the coronavirus globally, of which at least 84,000 have recovered from COVID-19, while more than 8,800 have died, according to data from Johns Hopkins University in the US.

 

Click here for Friday 20 March updates

20:00 GMT – Potential coronavirus treatment touted by Trump already in shortage -pharmacists

Supply of a malaria treatment that has been tried with some success against the new coronavirus is in short supply as demand surges amid the fast-spreading outbreak, according to independent pharmacies and the American Society of Health-System Pharmacists (ASHP).

The ASHP, which maintains a list of drugs in shortage independent of the U.S. Food and Drug Administration’s list, plans to add the generic malaria drug hydroxychloroquine to its list of shortages later on Thursday, according to Erin Fox, senior director of drug information at the University of Utah Health, who maintains the shortages list for the ASHP.

The FDA could not be immediately reached for comment, but hydroxychloroquine is not currently on its list of drugs in shortage.

President Donald Trump on Thursday called on US health regulators to expedite potential therapies aimed at treating COVID-19 for which there are no approved treatments or vaccines.

19:55 GMT – US sick leave aid leaves millions of workers in the cold

It’s usually standing room only at O’Duffy’s Pub on St Patrick’s Day, as patrons clad in green pack into the bar to share a drink or two and plenty of food. But this year, owner Jamie Kavanaugh and one of his bartenders sat alone on the holiday that commemorates Ireland’s patron saint. Like restaurants across the country, Kavanaugh’s Kalamazoo, Michigan, bar is now only allowed to serve takeout food as part of social distancing ordinances meant to curb the coronavirus pandemic.

“People are usually celebrating, smiling, toasting one another, sharing hugs and smiles. Instead, the pub is empty,” Kavanaugh told Al Jazeera. “People that came in for takeout didn’t even want to come in the door, and they’re afraid to use the pen to sign.”

Read more here.

19:50 GMT – Amazon shutters NYC warehouse after worker catches coronavirus

Amazon said it was closing a small New York City warehouse temporarily after one of its associates tested positive for the coronavirus, a move that highlights the operational risk it faces as the disease spreads.

The company said it has sent associates home from the delivery station with full pay as it sanitises the facility, its first in the United States known to have a case of the virus.

Read more here.

19:48 GMT – Israelis ordered to stay at home to halt coronavirus spread

Israeli Prime Minister Benjamin Netanyahu tightened a national stay-at-home policy, announcing guidelines aimed at halting the spread of the coronavirus would now be enforced by police under emergency orders.

“Under these orders, you, Israel’s citizens, are required to stay at home. It is no longer a request, it is not a recommendation, it is an obligatory directive that will be enforced by enforcement authorities,” Netanyahu said in a televised address.

The measures stopped short of a total national lockdown: Netanyahu said Israelis would still be allowed to shop for food and medicine, and some workers would be exempted from the restrictions.

Israel’s Health Ministry has reported 573 confirmed cases of coronavirus infection. 47 cases have been reported among Palestinians in the occupied West Bank.

19:40 GMT – US slaps sanctions on UAE-based firms over Iran oil purchases

The United States on Thursday slapped sanctions on five United Arab Emirates-based companies, accusing them of having collectively purchased hundreds of thousands of metric tons of petroleum products from Iran last year.

The move was the latest sign that Washington is showing no signs of backing away from squeezing Iran’s economy, even as the Islamic Republic struggles to battle the coronavirus outbreak.

Read more here.

19:18 GMT – Eight new coronavirus cases reported in Qatar, 10 recoveries

Qatar has announced eight new cases of COVID-19, and the recovery of 10, bringing the number of confirmed cases to 460, the ministry of health said.

The ministry also approved home quarantine as a second option for families arriving from abroad after passing a mandatory medical examination.

Until now 9,460 people have been tested for COVID-19 in Qatar.

19:05 GMT – France reports a huge spike in coronavirus deaths, raising total to 237

French SMUR rescue team wearing protective suits carry a patient at Strasbourg University hospital as France faces an aggressive progression of the coronavirus disease [Christian Hartmann/Reuters]

French health authorities reported 108 new deaths from coronavirus, taking the total to 372 or an increase of almost 41 percent, the toll rising sharply yet again as the country was in its third day of a lockdown aimed at containing the outbreak.

During a press conference, health agency director Jerome Salomon added the number of cases had risen to 10,995, up from 9,134 on Tuesday, which is a rise of 20 percent in 24 hours.

Salomon said 1,122 people were in a serious condition, needing life support, up 20.5 percent compared to Wednesday.

It is estimated France has around 5,000 beds equipped with the necessary gear but these are unevenly spread around the country.

Latest Update of Coronavirus

19:00 GMT – Coronavirus cases in Ireland rises to 557 from 366

The total number of confirmed cases of coronavirus in Ireland rose to 557 on Thursday from 366 a day earlier, the highest daily increase so far, the health department said.

“In broad terms, the total number of cases is not out of line with what we have predicted for the course of the week,” Ireland’s chief medical officer, Tony Holohan, told a news conference.

18:48 GMT – Number of coronavirus deaths in UK rises to 144

The number of people in the United Kingdom who have died after contracting the coronavirus rose to 144, up 40 percent in a day, the health ministry said.

The number of positive cases increased by 643, or 25 percent, to 3,269.

18:00 GMT – UK Queen urges Britons to ‘work as one’ to beat virus

Latest Update of Coronavirus

Queen Elizabeth II has moved to Windsor Castle outside of London due to coronavirus [File: Anadolu Agency]

Queen Elizabeth II said that “we all have a vitally important part to play” in battling the coronavirus crisis, in her first official message on the outbreak.

The Queen, who has been moved to Windsor Castle outside of London due to the virus, called on Britons to draw on their past as they enter “a period of great concern and uncertainty.”

“I am reminded that our nation’s history has been forged by people and communities coming together to work as one, concentrating our combined efforts with a focus on the common goal,” she said in a statement issued by Buckingham Palace.

“I am certain we are up to that challenge. You can be assured that my family and I stand ready to play our part,” she added.

17:40 GMT – 9,800 people in quarantine in Turkey

Latest Update of Coronavirus
A man looks out from a dormitory where he is placed in quarantine in response to the spreading of COVID-19 after returning from abroad, in Istanbul [Umit Bektas/Reuters]

Due to the COVID-19 outbreak, 9,800 people are currently under quarantine in Turkey, the interior minister said.

Speaking to the reporters in the parliament, Suleyman Soylu said the number of quarantined people, including pilgrims who returned from their Islamic pilgrimage of Umrah in Saudi Arabia, is 9,800 across the country.

Soylu also said 64 of 242 suspects allegedly posting fake and provocative coronavirus posts on social media were detained.

Turkey has so far reported 191 cases, with three deaths.

17:30 GMT – US CDC reports 10,491 coronavirus cases, 150 deaths

The US Centers for Disease Control and Prevention (CDC) has reported 10,491 cases of coronavirus, an increase of 3,404 cases from its previous count, and said the death toll had risen by 53 to 150.

Coronavirus cases have been reported in all 50 states and the District of Columbia.

The CDC figures do not necessarily reflect cases reported by individual states.

17:25 GMT – Italy overtakes China’s death toll

Italy’s death toll from an outbreak of coronavirus rose in the last 24 hours by 427 to 3,405, overtaking the total number of deaths so far registered in China, officials said.

Thursday’s figure represented a slight improvement on the day before, when Italy recorded 475 deaths.

Some 3,245 people have died in China since the virus first emerged there late last year. Italy’s outbreak came to light in the north of the country on February 21.

The total number of cases in Italy rose to 41,035 from a previous 35,713, up 14.9 percent, a faster rate of growth than seen over the last three days, the Civil Protection Agency said.

17:20 GMT – Trump presses FDA to fast-track potential coronavirus drugs

President Donald Trump called on US health regulators to expedite potential therapies aimed at treating COVID-19 amid the fast-spreading coronavirus outbreak, saying it could lead to a breakthrough while a vaccine is still under development.

Trump, speaking at a news conference, pointed to efforts on Gilead Sciences Inc’s experimental antiviral drug Remdesivir and the generic antimalarial drug hydroxychloroquine, saying he had called on the US Food and Drug Administration to streamline its regulatory approval process.

“We have to remove every barrier,” Trump said.

Trials on potential coronavirus therapies are already in the works and it was unclear how Trump’s call for faster experimental testing process could further expedite an effective treatment.

17:05 GMT – Egypt shuts all airports, suspends flights

Egypt has shut down its airports and air travel until March 31 to contain the outbreak of the coronavirus.

The new measures will heavily impact the country’s economy and tourism sectors, with some 138,000 jobs immediately at risk and a loss of $1bn in airline revenues, according to IATA.

No tourists were in sight near Giza’s pyramids, Egypt’s iconic landmarks, and coffee shops and restaurants were shuttered in Cairo, a city of over 20 million.

Egypt, which has reported nearly 210 cases and six deaths from the virus, has suspended flights, closed schools, and is quarantining more than 300 families in a Nile Delta village, and imposed a lockdown in the Red Sea resort town of Hurghada.

16:55 GMT – Sharp increase in Moscow pneumonia cases

A reported sharp increase in pneumonia cases in the Russian capital and contradictory information around the issue is fuelling fears about the accuracy of official coronavirus data as it remains much lower than many European countries.

Russia, which has a population of 144 million, has reported just 199 coronavirus cases and some doctors have questioned how far the official data reflects reality, given what they say is the patchy nature and quality of testing.

A spike in pneumonia cases in Moscow, Russia’s biggest transport hub and a city with a population of about 13 million, has further raised doubts.

“I have a feeling they [the authorities] are lying to us,” said Anastasia Vasilyeva, head of Russia’s Doctor’s Alliance trade union.

The government, however, says its statistics are accurate and President Vladimir Putin has complained that Russia is being targeted by fake news to sow panic.

16:42 GMT – South Africa to erect 40km fence on Zimbabwe border

South African authorities announced they would erect a fence along its border with Zimbabwe to prevent undocumented immigrants from entering and spreading the coronavirus.

President Ramaphosa has already ordered 35 out of 53 land entry points closed.

“This measure will … not be effective if the fences at the border are not secure, which in many places, they are not,” Public Works Minister Patricia de Lille said in a statement.

South Africa has long sought to reduce irregular migration from Zimbabwe, which it sees as a threat to local jobs in a country with unemployment of around 30 percent.

15:45 GMT – ‘Quarantine shaming’: US navigates radical new social norms

“Quarantine shaming” – calling out those not abiding by social distancing rules – is part of a new and startling reality for Americans who must navigate a world of rapidly evolving social norms in the age of COVID-19.

As schools close and shelter-in-place orders sweep across the US, the divide between those who are stringently practicing self-isolation and those still trying to go about some semblance of normal life has never been clearer.

Complicating matters, what was socially acceptable even 48 hours ago may now be taboo, as government officials race to contain the virus with ever-expanding circles of social isolation.

“The time matrix seems to be shifting. I’ve never known several days to go by so slowly and watching the collective conscience move more and more in one direction day by day,” said Paula Flakser, who lost her bartending job when California’s Mammoth Mountain ski resort closed this week.

15:30 GMT – Africa sees ‘extremely rapid evolution’ of the pandemic, UN says

More African countries closed their borders on Thursday as the coronavirus’s local spread threatened to turn the continent of 1.3 billion people into an alarming new front for the pandemic.

“About 10 days ago we had about five countries” with the virus, WHO’s Africa chief Dr Matshidiso Moeti told reporters. Now 34 of Africa’s 54 countries have cases, with the total close to 650. It is an “extremely rapid evolution”, she said.

15:05 GMT – Iran’s death toll from coronavirus rises to 1,284

Members of firefighters wear protective face masks amid fear of COVID-19, as they disinfect the streets before the Iranian New Year Nowruz in Tehran [Ali Khara/ WANA via Reuters]

The new coronavirus is killing one person every 10 minutes in Iran, a health ministry spokesman said, as the death toll in the Middle East’s worst-affected country climbed to 1,284.

“Based on our information, every 10 minutes one person dies from the coronavirus and some 50 people become infected with the virus every hour in Iran,” Kianush Jahanpur tweeted.

Iran’s Deputy Health Minister Alireza Raisi said the total number of infections had reached 18,407 in the Islamic republic.

The virus has also dampened Iran’s celebrations for the Nowruz New Year that begins on Friday. Authorities have urged people to stay home and avoid traveling during the holiday period to help contain the spread.

14:45 GMT – English Premier League further postponed until April 30

Latest Update of Coronavirus
A view inside the Premier League headquarters in London [Justin Setterfield/Getty Images]

The FA, Premier League and EFL announced that the suspension of English football has been extended until at least April 30 amid the coronavirus pandemic. The statement also revealed that the current season will be “extended indefinitely”.

“The progress of Covid-19 remains unclear and we can reassure everyone the health and welfare of players, staff and supporters are our priority,” a statement said.

The FA’s rules and regulations state the season shall terminate no later than the June 1 but it was agreed this can be “extended indefinitely” for the 2019-20 campaign.

14:30 GMT – Wall Street and Main Street on watch to see if Trump gains erased

US stocks extended their losses on Thursday, opening lower on the heels of Wednesday’s session that saw the Dow Jones Industrial Average close below 20,000 for the first time since February 2017 – a hair’s breadth from erasing all of its gains since President Donald Trump took office.

Trump has touted the performance of the Dow throughout his presidency, taking credit for the economy’s continued expansion – now in its 11th year – and for the stock market marking new record highs. But what went up, coronavirus is now bringing down – with a vengeance.

Read more here.

14:25 GMT – France says no hugging loved ones

A couple sits in a restaurant, as France's Prime Minister announced to close most all non-indispensable locations, notably cafes, restaurants, cinemas, nightclubs and shops from midnight in Nice
A couple sit in a restaurant in Nice, France even as the country closed almost all non-indispensable locations, notably cafes, restaurants, cinemas, nightclubs and shops due to concerns over the coronavirus disease [File: Eric Gaillard/Reuters]

French Prime Minister Edouard Philippe pleaded for people to keep their distance from one another to avoid spreading the virus, even as the crisis pushed them to seek comfort.

“When you love someone, you should avoid taking them in your arms,” he said in parliament. “It’s counterintuitive, and it’s painful; the psychological consequences, the way we are living, are very disturbing – but it’s what we must do.”

14:15 GMT – Italy’s death toll nears China’s

Italy, a country of 60 million, registered 2,978 deaths on Wednesday after 475 people died in a day. Given that Italy has been averaging more than 350 deaths a day since March 15, it is likely to overtake China’s 3,249 dead – in a country of 1.4 billion – when Thursday’s figures are released.

The United Nations and Italian health authorities have cited a variety of reasons for Italy’s high toll, key among them its large elderly population that is particularly susceptible to developing serious complications from the virus. Italy has the world’s second-oldest population after Japan and the vast majority of Italy’s dead – 87 percent – were over age 70.

Jonas Schmidt-Chanasit, a virologist at Germany’s Bernhard Nocht Institute for Tropical Medicine, said Italy’s high death rate could be explained in part by the almost total collapse of the health system in some parts.

“And then people die who wouldn’t have died with timely intervention,” he said. “That’s what happens when the health system collapses.”

14:00 GMT – Thousands rush to leave the Philippines amid month-long lockdown

Passengers wearing masks stand by with their luggage outside the Ninoy Aquino International Airport in Paranaque, Metro Manila
Passengers wearing masks stand by with their luggage outside the Ninoy Aquino International Airport in Paranaque, Metro Manila, amid fears of COVID-19 spreading in the Philippines [Eloisa Lopez/Reuters]

Thousands of people have rushed to the main international airport of the Philippines in a bid to get out of the country amid a month-long lockdown on the main island designed to stop the spread of the new coronavirus.

Foreigners and Filipinos crowded Ninoy Aquino International Airport in Manila to try to get on a flight out of the country, where 217 cases of COVID-19 have been confirmed, with 17 deaths.

The exodus came as Foreign Secretary Teodoro Locsin announced the Philippines was temporarily suspending the issuance of visas to all foreigners.

“Starting today, all our embassies and consulates will temporarily suspend visa issuance to all foreign nationals as well as the visa-free entry privileges of all foreign nationals,” he said.

13:45 GMT – Panic buying forces South African supermarkets to ration food

A supermarkets vegetable racks are empty as people stock up on food after the government announced measures to curb coronavirus infections in Hillcrest
A supermarket’s vegetable racks are empty as people stock up on food after the government announced measures to curb coronavirus infections in Hillcrest, South Africa [Rogan Ward/Reuters]

South Africa’s biggest supermarket Shoprite said it will limit the purchase of some food products and medicines as frantic shoppers emptied shelves to prepare for possible isolation during the coronavirus outbreak.

As the spread of the infection triggers panic buying across the world, South African retailers are saying they are working with their suppliers to ensure a consistent supply of products like meat and canned food, and medicine.

To ensure more people have access to everyday essentials, Shoprite said it is now rationing the sale of toilet paper, tissues, wipes, liquid soap, hand sanitizer as well as some tinned foods, cereals, antiseptic disinfectant liquids, medicines and vitamins.

13:32 GMT – South Asia snapshot: How bad is the coronavirus outbreak?

South Asian countries are beginning to see their first deaths from the coronavirus outbreak, with COVID19 claiming at least six lives across the region amid a spike in cases in Pakistan and elsewhere.

The outbreak does not appear to have reached the widespread secondary contact stage seen in Europe and the US – and earlier in China and South Korea – yet, but cases are continuing to rise as governments across the region scramble to enforce social distancing guidelines.

Read more here.

13:28 GMT – Dutch PM tells citizens there is enough toilet paper for 10 years

The prime minister of the Netherlands told citizens on Thursday there is no shortage of toilet paper.

“Yes, I have enough,” Mark Rutte told a shopper in an informal exchange while visiting a supermarket to show support for workers. “They have it [on shelves] again.”

“But there’s enough in the whole country for the coming 10 years,” he said. “We can all poop for 10 years.”

Dutch supermarkets’ shelves have mostly refilled following a stockpiling episode last week.

12:40 GMT – Experts say Somalia under great coronavirus risk

Medical experts and analysts warn that the coronavirus pandemic could kill more people in Somalia than anywhere else if preventive measures are not put in place urgently.

The East African country confirmed its first case of COVID-19 on Monday in a student who returned from China.

Read more here.

12:33 GMT – EU’s top Brexit negotiator Barnier tests positive

The European Union’s chief negotiator for Brexit, Michel Barnier, said he had tested positive for COVID-19, the disease caused by the novel coronavirus.

“I would like to inform you that I have tested positive for COVID-19. I am doing well and in good spirits. I am following all the necessary instructions, as is my team,” he said on Twitter.

I would like to inform you that I have tested positive for #COVID19. I am doing well and in good spirits. I am following all the necessary instructions, as is my team.

For all those affected already, and for all those currently in isolation, we will get through this together.

— Michel Barnier (@MichelBarnier) March 19, 2020

12:10 GMT – India bars international commercial passenger flights

India’s government said it will ban all scheduled international commercial passenger flights from landing in the country from March 22 for one week to contain the spread of the coronavirus.

India has already suspended visas for the vast majority of foreigners seeking to enter the country.

11:52 GMT – Spain’s coronavirus death toll climbs by over 200 in a day

Spain’s health ministry said the death toll from the coronavirus epidemic soared by 209 to 767 fatalities from the previous day.

A total of 17,147 people have contracted the disease in the country, a roughly 25 percent increase over the previous day, according to the health ministry, with the figure expected to rise further in the coming days as testing for COVID-19 becomes more readily available.

There were 13,716 cases in Spain on Wednesday.

11:40 GMT – Africa told to prepare for worst

From imposing travel bans to prohibiting mass gatherings and shutting down schools, governments across Africa are increasingly adopting sweeping measures in a bid to curb the spread of the new coronavirus.

However, experts warn that the number of cases in the continent was likely higher and urge African countries to “wake up” to the increasing threat.

Read more here.

Latest Update of Coronavirus

Experts say African countries should prepare for the worst [Feisal Omar/Reuters]

11:26 GMT – the Netherlands tests blood samples for unseen coronavirus spread

Dutch health authorities have begun a major project testing blood donation samples to see how many people in the Netherlands may have already had the new coronavirus.

The project is being carried out on 10,000 blood donation samples a week by blood bank Sanquin, in cooperation with the country’s National Institute for Health (RIVM).

“It’s possible that you had coronavirus without being sick,” Sanquin spokesman Merlijn van Hasselt told national broadcaster NOS. “If we test for antibodies, we can see whether you’ve already had it … and over time get a picture of how that’s evolving.”

So far there have been 2,051 cases in the Netherlands of COVID-19 and 58 deaths [Jean-Pierre Geusens/ANP/AFP]

11:20 GMT – Coronavirus coping mechanisms from around the world

People around the world are trying to cope with the coronavirus pandemic as it rapidly spreads.

Here is a collection of wonderful and sometimes odd coping mechanisms from around the globe.

10:58 GMT – South Korea pledges $39bn funding for small businesses

Latest Update of Coronavirus

South Korean President Moon Jae-in pledged 50 trillion won ($39bn) in emergency financing for small businesses and other stimulus measures to prop up the coronavirus-hit economy.

The package is the latest in a string of steps the South Korean government has taken to curb pressure on Asia’s fourth-largest economy, including an interest rate cut, an extra 11.7 trillion won ($9.12bn) budget and more dollar supplies.

The government will issue loan guarantees for struggling small businesses with less than 100 million won ($78,000) in annual revenue to ensure they can easily and cheaply get access to credit, Moon said.

09:57 GMT – Sri Lanka defers elections

Sri Lanka will not conduct the parliamentary elections as scheduled on April 25 due to the coronavirus outbreak, Mahinda Deshapriya, the chairman of the country’s election commission, said.

The government earlier this week banned all incoming flights for two weeks and imposed a curfew in some areas to rein in the spread of the disease.

There have been over 50 confirmed cases of coronavirus in Sri Lanka so far.

09:55 GMT -Trump defends calling coronavirus the ‘Chinese virus’

US President Donald Trump has been criticised for repeatedly referring to the coronavirus as the “Chinese Virus”, with critics saying he is “fuelling bigotry” and putting Asian-American communities at risk.

However, Trump defends his labelling of the pandemic. Here is how:

09:43 GMT – Thailand reports 60 new cases

Thailand recorded 60 new coronavirus cases in the biggest daily jump in the number of cases so far to take its total infections to 272, a health official said.

The new cases fall into two groups, the first consists of 43 cases linked to earlier cases, while the second group involves 17 new patients including arrivals from countries such as Italy, Malaysia, Japan, Iran and Taiwan, Suwannachai Wattanayingcharoenchai, director-general of Department of Disease Control at the Ministry of Health, told a news conference.

Thailand has recorded one death since the outbreak, with 42 patients having recovered and gone home and 229 still being treated in hospital.

09:22 GMT – Israel: Palestinian prisoners contracted coronavirus

Israeli authorities and Palestinian local media said that four Palestinian prisoners had coronavirus infection.

The cases were contracted in Megiddo prison in Israel, reports said.

09:22 GMT – Malaysia reports 110 new cases

Malaysia reported 110 new coronavirus cases, with the total number of cases increasing to 900.

Most of the new cases were linked to a religious gathering at a mosque attended by 16,000 people, the health ministry said.

epaselect epa08302952 Security officers check the tempature of visitors inside a closed shopping mall during the first day of a movement control order issued by the Malaysia government, Malaysia, 18 M
Security officers check the temperature of visitors inside a mall during the first day of a movement control order issued by the Malaysia government [Fazry Ismail/EPA]

09:15 GMT – A journalist’s story of making her way home before lockdown

Manila-based journalist Ana Santos was attending a training program in El Salvador when the coronavirus pandemic started around the world.

The program was canceled and she had to return to her country, the Philippines, immediately.

She had a little more than 48 hours to take a nearly 24-hour-long flight to Manila before the whole country was sealed off.

Here, she describes the hurdles she went through trying to get home as the pandemic accelerated.

08:53 GMT – All you need to know about coronavirus

According to the WHO, coronaviruses are a family of viruses that cause illnesses ranging from the common cold to more severe diseases such as severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS).

WHO says signs of infection include fever, cough, shortness of breath and breathing difficulties.

Here is all you need to know about the coronavirus.

08:40 GMT – PM Conte: Italy to prolong anti-coronavirus lockdown

Italy will remain under lockdown beyond previous deadlines due to expire later this month and in early April, Prime Minister Giuseppe Conte said.

In comments to the Corriere della Sera newspaper, Conte said measures taken to close schools, universities and to impose severe restrictions on movement would have to be prolonged.

Under current measures, Italy’s 60 million people are only allowed to travel for work, medical reasons or emergencies under an order that runs until April 3, while most shops, except those selling food and pharmacies, are supposed to remain closed until March 25.

07:10 GMT – Russia reports first coronavirus death

Russia said a 79-year-old woman with underlying health issues, who tested positive for the new coronavirus, had died from pneumonia, the country’s first confirmed death resulting from the virus.

Russia has so far reported 147 cases of the coronavirus.

Read more here.

06:35 GMT – Up to 20,000 UK military personnel to go on standby

Up to 20,000 British military service personnel will be put on standby to help tackle the coronavirus outbreak, the defence ministry said.

The number represented a doubling of service personnel who are on standby.

06:15 GMT – Medical volunteers spread coronavirus awareness in Syria

As the coronavirus takes a firmer hold across the Middle East, there is growing concern that war-torn Syria might face a major outbreak.

As concerns over a possible catastrophic prospect grow, a group of medical volunteers in northern Syria teach displaced Syrians how to help prevent catching coronavirus.

06:00 GMT – German minister tested negative for coronavirus

German Finance Minister Olaf Scholz said that his test for the coronavirus came back negative.

Scholz added in a tweet that his cold was subsiding slowly and that he would join discussions at Chancellor Angela Merkel’s office on Thursday.

“The #corona crisis is challenging us all – together we can weather it. Our country can do it,” Scholz added. Die Stimme ist noch mitgenommen, die Erkältung geht etwas zurück und der Test war negativ. Vielen Dank für die vielen guten Wünsche. Heute kein Homeoffice, sondern Beratungen im Kanzleramt. Die #Corona-Krise fordert und alle – gemeinsam stehen wir das durch. Unser Land kann das.

— Olaf Scholz (@OlafScholz) March 19, 2020

05:45 GMT – Lufthansa: Airlines might not survive without state aid

Lufthansa said that the airline industry may not survive without state aid if the coronavirus epidemic lasts for a long time.

The German airline group has slashed capacity, proposed short-time working and suspended its dividend, saying it was impossible to forecast the impact of coronavirus on profitability.

“The spread of the coronavirus has placed the entire global economy and our company as well in an unprecedented state of emergency,” CEO Carsten Spohr said in a statement.

“At present, no one can foresee the consequences.”

04:55 GMT – India’s PM to address nation

India’s Prime Minister Narendra Modi will make a national address on the coronavirus at 8pm (14:30 GMT), he announced on his official Twitter account.

04:50 GMT – World Bank increases virus response package to $14bn

The World Bank has increased its support package for businesses and economies struggling with the impact of the coronavirus.

04:10 GMT – Hokkaido ending state of emergency

Japanese public broadcaster NHK is reporting that an expert panel guiding Japan’s coronavirus response may advise a relaxation of controls in regions that have not seen outbreaks, as the northern island of Hokkaido ends its state of emergency.

The infectious disease experts are due to meet later on Thursday.

Japan, which is due to host the Olympics in July, has insisted it will press ahead with the games even though the pandemic has brought the sports world almost to a standstill.

Latest Update of Coronavirus
Japan’s northern island of Hokkaido is lifting a state of emergency declared over the coronavirus [File: Issei Kato/Reuters]

Hokkaido had 154 infections as of Wednesday. Among Japan’s 47 prefectures, 22 have had fewer than 5 coronavirus cases, according to health ministry data.

04:00 GMT – WHO responds on ibuprofen concerns

The WHO has said it is discussing concerns about the use of ibuprofen to treat fever in patients with COVID-19 and is not aware of any negative effects.

It is not recommending against its use.

Q: Could #ibuprofen worsen disease for people with #COVID19?

A: Based on currently available information, WHO does not recommend against the use of of ibuprofen. pic.twitter.com/n39DFt2amF

— World Health Organization (WHO) (@WHO) March 18, 2020

03:55 GMT – Indonesia must ramp up testing – Joko Widodo

Indonesia’s President Joko Widodo says the Southeast Asian nation needs to immediately widen its testing for coronavirus after the country reported 55 new cases on Wednesday.

“I ask that the number of testing kits and the number of test centers are increased and we get more hospitals involved,” Widodo said.

Indonesia has recorded a total of 227 cases so far.

02:30 GMT – Government steps in to call off mass Muslim event in Indonesia

Indonesian authorities have succeeded in convincing a group of Muslim pilgrims to call off a mass rally amid fears it could fuel the spread of the coronavirus.

Officials have spent days trying to get Ijtima Asia, part of the global Tablighi Jama’at movement, to stop the event with 8,500 people already gathering near Makassar in eastern Indonesia.

A similar event in Malaysia which attracted more than 16,000 people led to a surge in cases, not only in Malaysia but also in other Southeast Asian countries.

02:20 GMT – Qantas to halt all international flights from late March

Two-thirds of staff at Australian airline Qantas have been told to go home, with the airline stopping all international flights from the end of March until at least the end of May.

“This is a terrible day that we have to make these decisions on the survival of the national carrier,” the airline’s chief executive Alan Joyce told reporters. “I never thought as a CEO I would have to stand down two-thirds of our people.”

Some domestic flights will continue.

02:10 GMT – New Zealand tells citizens ‘Do not travel’

New Zealanders have been told not to travel given the heightened risk of contracting the coronavirus overseas.

“We are raising our travel alert to the highest level: do not travel,” Foreign Minister Winston Peters said in a statement. “This is the first time, the New Zealand government has advised New Zealanders against traveling anywhere overseas. That reflects the seriousness of the situation we are facing with COVID-19.”

He also urged New Zealanders already overseas to return home.

02:05 GMT – South Korea reports jump in cases after four days of slowing infections

Latest data from South Korea shows a jump in new coronavirus cases with a new outbreak emerging n a nursing home in the hardest-hit city of Daegu.

The Korea Centers for Disease Control and Prevention reported 152 new cases, taking the national tally to 8,565.

The country had recorded fewer than 100 new infections for four days in a row until Wednesday.

Among the new cases, 97 are from Daegu, where the KCDC said at least 74 patients at a nursing home tested positive for the virus this week.

The KCDC did not specify how many of the new cases were linked to the nursing home directly.

The fresh outbreak has prompted Daegu officials to launch extensive checks on all other nursing homes.

01:45 GMT – China reports only imported cases, mostly in Beijing

China’s new cases of coronavirus underscore how the nature of the outbreak has shifted.

The National Health Commission says while there were no domestic cases reported on Wednesday, there were 34 confirmed cases among people returning from overseas. That compares with 13 the day before.

Of the 34 imported infections, 21 were in Beijing.

That brings the total number of confirmed cases in mainland China so far to 80,928.

The death toll rose by eight to 3,245 as of the end of Wednesday.

01:30 GMT – Wuhan and Hubei report no new cases of coronavirus for first time

China’s central city of Wuhan and its surrounding province of Hubei have reported no new cases of coronavirus for the first time.

COVID-19 is thought to have originated in a now-closed seafood market that also sold wildlife late last year.

NO new infections of the novel #coronavirus were reported on Wednesday in #Wuhan, marking a notable first in the city’s months-long battle with the virus. pic.twitter.com/vJ33KQviV9

— Global Times (@globaltimesnews) March 19, 2020

00:30 GMT – US and Canada close border to all but essential traffic

The US and Canada have closed their border to non-essential traffic.

Latest Update of Coronavirus

The US and Canada have closed their border to all but essential traffic [Rebecca Cook/Reuters]

00:20 GMT – Trump signs coronavirus response bill

The White House says US President Donald Trump has signed the coronavirus response bill that will allow for free testing and paid sick leave for those working in companies with below 500 employees.

That excludes giant firms like Amazon, McDonald’s and Walmart.

00:05 GMT – Hong Kong introduces compulsory quarantine for all overseas arrivals

Hong Kong has tightened rules for people arriving from overseas.

The territory’s reported a rising number of imported cases and all arrivals will now be required to spend 14 days in quarantine on their arrival in Hong Kong.

The authorities are also urging the city’s residents not to travel.

00:00 GMT – UK to close schools from Friday

The United Kingdom is to close all schools from Friday and cancel national exams, as it ramps up efforts to curb the spread of the coronavirus.

Education Secretary Gavin Williamson told parliament that the situation had become increasingly challenging.

“The spike of the virus is increasing at a faster pace than anticipated,” he said.

In London, which has reported nearly 1,000 cases of the coronavirus, the underground service’s night network – a more limited service – will also be closed down.

I’mKate Mayberryin Kuala Lumpur with Al Jazeera’s continuing coverage of the unfolding coronavirus pandemic.

For all the updates from yesterday (March 18), please click here.

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Stem Cell Therapies – FDA Warns About Stem Cell Therapies

Stem Cell Therapies /Researchers hope stem cells will one day be effective in the treatment of many medical conditions and diseases. But unproven stem cell treatments can be unsafe—so get all of the facts if you’re considering any treatment.

Stem cells have been called everything from cure-alls to miracle treatments. But don’t believe the hype. Some unscrupulous providers offer stem cell products that are both unapproved and unproven. So beware of potentially dangerous procedures—and confirm what’s really being offered before you consider any treatment.

The facts: Stem cell therapies may offer the potential to treat diseases or conditions for which few treatments exist. Sometimes called the body’s “master cells,” stem cells are the cells that develop into blood, brain, bones, and all of the body’s organs. They have the potential to repair, restore, replace, and regenerate cells, and could possibly be used to treat many medical conditions and diseases.

But the U.S. Food and Drug Administration is concerned that some patients seeking cures and remedies are vulnerable to stem cell treatments that are illegal and potentially harmful. And the FDA is increasing its oversight and enforcement to protect people from dishonest and unscrupulous stem cell clinics while continuing to encourage innovation so that the medical industry can properly harness the potential of stem cell products.

To do your part to stay safe, make sure that any stem cell treatment you are considering is either

  • FDA-approved, or;
  • Being studied under an Investigational New Drug Application (IND), which is a clinical investigation plan submitted and allowed to proceed by the FDA.

Stem Cell Uses and FDA Regulation

The FDA has the authority to regulate stem cell products in the United States.

Today, doctors routinely use stem cells that come from bone marrow or blood in transplant procedures to treat patients with cancer and disorders of the blood and immune system.

Photo taken through microscope (electron micrograph) of four round stem cells with slightly bumpy surfaces, colored yellow against a green background to enhance visual clarity.
Electron micrograph of stem cells, color-enhanced for visual clarity.

With limited exceptions, investigational products must also go through a thorough FDA review process as investigators prepare to determine the safety and effectiveness of products in well-controlled human studies, called clinical trials. The FDA has reviewed many stem cell products for use in these studies.

As part of the FDA’s review, investigators must show how each product will be manufactured so the FDA can make sure appropriate steps are being taken to help assure the product’s safety, purity, and strength (potency). The FDA also requires sufficient data from animal studies to help evaluate any potential risks associated with product use. (You can learn more about clinical trials on the FDA’s website.)

That said, some clinics may inappropriately advertise stem cell clinical trials without submitting an IND. Some clinics also may falsely advertise that FDA review and approval of the stem cell therapy is unnecessary. But when clinical trials are not conducted under an IND, it means that the FDA has not reviewed the experimental therapy to help make sure it is reasonably safe. So be cautious about these treatments.

About FDA-approved Products Derived from Stem Cells

The only stem cell-based products that are FDA-approved for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood.

These products are approved for limited use in patients with disorders that affect the body system that is involved in the production of blood (called the “hematopoietic” system). These FDA-approved stem cell products are listed on the FDA website. Bone marrow also is used for these treatments but is generally not regulated by the FDA for this use.

Safety Concerns for Unproven Stem Cell Treatments

All medical treatments have benefits and risks. But unproven stem cell therapies can be particularly unsafe.

For instance, attendees at a 2016 FDA public workshop discussed several cases of severe adverse events. One patient became blind due to an injection of stem cells into the eye. Another patient received a spinal cord injection that caused the growth of a spinal tumor.

Other potential safety concerns for unproven treatments include:

  • Administration site reactions,
  • The ability of cells to move from placement sites and change into inappropriate cell types or multiply,
  • Failure of cells to work as expected, and
  • The growth of tumors.

Note: Even if stem cells are your own cells, there are still safety risks such as those noted above. In addition, if cells are manipulated after removal, there is a risk of contamination of the cells.

FDA Actions on Unapproved Stem Cell Products

When stem cell products are used in unapproved ways—or when they are processed in ways that are more than minimally manipulated, which relates to the nature and degree of processing—the FDA may take (and has already taken) a variety of administrative and judicial actions, including criminal enforcement, depending on the violations involved.

In August 2017, the FDA announced increased enforcement of regulations and oversight of stem cell clinics. To learn more, see the statement from FDA Commissioner Scott Gottlieb, M.D., on the FDA website.

And in March 2017, to further clarify the benefits and risks of stem cell therapy, the FDA published a perspective article in the New England Journal of MedicineExternal Link Disclaimer.

The FDA will continue to help with the development and licensing of new stem cell therapies where the scientific evidence supports the product’s safety and effectiveness.

Advice for People Considering Stem Cell Therapies

Know that the FDA plays a role in stem cell treatment oversight. You may be told that because these are your cells, the FDA does not need to review or approve the treatment. That is not true.

Stem cell products have the potential to treat many medical conditions and diseases. But for almost all of these products, it is not yet known whether the product has any benefit—or if the product is safe to use.

If you’re considering treatment in the United States:

  • Ask if the FDA has reviewed the treatment. Ask your health care provider to confirm this information. You also can ask the clinical investigator to give you the FDA-issued Investigational New Drug Application number and the chance to review the FDA communication acknowledging the IND. Ask for this information before getting treatment—even if the stem cells are your own.
  • Request the facts and ask questions if you don’t understand. To participate in a clinical trial that requires an IND application, you must sign a consent form that explains the experimental procedure. The consent form also identifies the Institutional Review Board (IRB) that assures the protection of the rights and welfare of human subjects. Make sure you understand the entire process and known risks before you sign. You also can ask the study sponsor for the clinical investigator’s brochure, which includes a short description of the product and information about its safety and effectiveness.

If you’re considering treatment in another country:

  • Learn about regulations that cover products in that country.
  • Know that the FDA does not have oversight of treatments done in other countries. The FDA typically has little information about foreign establishments or their stem cell products.
  • Be cautious. If you’re considering a stem cell-based product in a country that may not require regulatory review of clinical studies, it may be hard to know if the experimental treatment is reasonably safe.

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What Are The Most Common Side Effects of Antibiotics

What Are The Most Common Side Effects of Antibiotics

What Are The Most Common Side Effects of Antibiotics/Antibiotics also called an antibacterial type of antimicrobial drug used in the treatment and prevention of bacterial infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.

You’ve most likely taken an antibiotic at least once in your lifetime. From treatments for painful strep throat or ear infections as a child, to burning urinary tract infections or itchy skin infections as an adult, antibiotics are one of the most highly utilized and important medication classes we have in medicine.

Understanding the vast world of antibiotics and anti-infectives is no easy task. Anti-infectives are a large class of drugs that cover a broad range of infections, including fungal, viral, bacterial, and even protozoal infections. Athletes foot? That’s a common fungal infection. HIV? Antiviral medications are always needed. Bladder infection? Yes, that may need a common antibiotic. And head lice? A topical anti-parasitic can alleviate the itching. There is no one type of antibiotic that cures every infection. Antibioticsspecifically treat infections caused by bacteria, such as Staph., Strep., or E. coli., and either kill the bacteria (bactericidal) or keep it from reproducing and growing (bacteriostatic). Antibiotics do not work against any viral infection.

When To Use Antibiotics

Antibiotics are specific for the type of bacteria being treated and, in general, cannot be interchanged from one infection to another. When antibiotics are used correctly, they are usually safe with few side effects.

However, as with most drugs, antibiotics can lead to side effects that may range from being a nuisance to serious or life-threatening. In infants and the elderly, in patients with kidney or liver disease, in pregnant or breastfeeding women, and in many other patient groups antibiotic doses may need to be adjusted based upon the specific characteristics of the patient, like kidney or liver function, weight, or age. Drug interactions can also be common with antibiotics. Health care providers are able to assess each patient individually to determine the correct antibiotic and dose.

When NOT To Use Antibiotics

Antibiotics are not the correct choice for all infections. For example, most sore throats, cough and colds, flu or acute sinusitis are viral in origin (not bacterial) and do not need an antibiotic. These viral infections are “self-limiting”, meaning that your own immune system will usually kick in and fight the virus off. In fact, using antibiotics for viral infections can increase the risk for antibiotic resistance, lower the options for future treatments if an antibiotic is needed, and put a patient at risk for side effects and extra cost due to unnecessary drug treatment.

Antibiotic-resistant bacteria cannot be fully inhibited or killed by an antibiotic, even though the antibiotic may have worked effectively before the resistance occurred. Don’t share your antibiotic or take medicine that was prescribed for someone else, and don’t save an antibiotic to use the next time you get sick.

Antibiotics Classification

Although there are several systems for classification of antibiotics, the most useful is based on chemical structure. Antibiotics within a structural class will generally have similar patterns of effectiveness, toxicity, and allergic potential.

The main classes of antibiotics are:

  • Beta-Lactams
    • Penicillins
    • Cephalosporins
  • Macrolides
  • Fluoroquinolones
  • Tetracyclines
  • Aminoglycosides

Most commonly used types of antibiotics are: Aminoglycosides, Penicillins, Fluoroquinolones, Cephalosporins, Macrolides, and Tetracyclines. While each class is composed of multiple drugs, each drug is unique in some way.

Penicillins

The penicillins are the oldest class of antibiotics. Penicillins are bicyclic penam compounds and share their chemical structure with the cephalosporins.

Penicillins are generally bactericidal, inhibiting the formation of the bacterial cell wall. Penicillins are used to treat skin infections, dental infections, ear infections, respiratory tract infections, urinary tract infections, and gonorrhea.

There are four types of penicillins:

  • The natural penicillins are based on the original penicillin-G structure. Natural penicillins are active against gram-positive streptococci, staphylococci, and some gram-negative bacteria such as meningococcus.
  • Penicillinase-resistant penicillins (e.g. methicillin, oxacillin) are active against beta-lactamase producing bacteria, that inactivates most penicillin antibiotics.
  • Aminopenicillins such as ampicillin and amoxicillin are effective against a wider range of bacteria and have a better oral absorption.
  • Extended-spectrum penicillins (e.g. mezlocillin, piperacillin, ticarcillin).
Penicillins side effects

Penicillins are generally very safe drugs with minimum toxicity. Their most common side effect is diarrhea. Nausea, vomiting, and upset stomach are also common. In rare cases penicillins can cause immediate or delayed allergic reactions which manifest as skin rashes, fever, angioedema, and anaphylactic shock. Severe hypersensitivity reactions are more common after injections than after oral formulations.

Neurotoxicity

Very high doses of penicillins, especially in patients with renal impairment, may cause convulsions.

All penicillins are classed as Pregnancy category B.

Cephalosporins

Cephalosporins have a mechanism of action identical to that of the penicillins. However, the basic chemical structure of the penicillins and cephalosporins differs in other respects, resulting in different spectrum of antibacterial activity. Like the penicillins, cephalosporins have a beta-lactam ring structure that interferes with synthesis of the bacterial cell wall and so are bactericidal. Cephalosporins are derived from cephalosporin C which is produced from Cephalosporium acremonium.

Cephalosporins are used to treat pneumonia, strep throat, staph infections, tonsillitis, bronchitis, otitis media, various types of skin infections, gonorrhea, urinary tract infections Cephalosporin antibiotics are also commonly used for surgical prophylaxis. Cephalexin can also be used to treat bone infections.

Cephalosporins are extremely diverse class of antibiotics, they are grouped into “generations” by their antimicrobial properties. Each newer generation has a broader spectrum of activity than the one before.

The first-generation – cephalosporins have quite similar spectrums of activity. They have excellent coverage against most gram-positive pathogens but variable to poor coverage against most gram-negative pathogens. The first generation includes:

  • cephalothin
  • cefazolin
  • cephapirin
  • cephradine
  • cephalexin
  • cefadroxil

The second-generation cephalosporins have expanded gram-negative spectrum in addition to the gram-positive spectrum of the first-generation cephalosporins. Cefoxitin and cefotetan have good activity against Bacteroides fragilis. Enough variation exists between the second generation cephalosporins in regard to their spectrums of activity against most species of gram-negative bacteria, that susceptibility testing is generally required to determine sensitivity. The second generation includes:

  • cefaclor
  • cefamandole
  • cefonicid
  • ceforanide
  • cefuroxime

The third-generation cephalosporins have much expanded gram-negative activity. However, some members of this group have decreased activity against gram-positive organisms. They have the advantage of convenient dosage regimen, but they are expensive. The third-generation includes:

  • cefcapene
  • cefdaloxime
  • cefditoren
  • cefetamet
  • cefixime
  • cefmenoxime
  • cefodizime
  • cefoperazone
  • cefotaxime
  • cefpimizole
  • cefpodoxime
  • ceftibuten
  • ceftriaxone

The fourth-generation cephalosporins are extended-spectrum agents with similar activity against gram-positive organisms as first-generation cephalosporins. They also have a greater resistance to beta-lactamases. Many fourth-generation cephalosporins can cross blood-brain barrier and are effective in meningitis. The fourth-generation includes:

  • cefclidine
  • cefepime
  • cefluprenam
  • cefozopran
  • cefpirome
  • cefquinome
Cephalosporins side effects
  • Cephalosporins are the remarkably safe class of antibiotics and usually cause few adverse effects. Common side effects include diarrhea, nausea, mild stomach cramps or upset. Approximately 5–10% of patients with allergic hypersensitivity to penicillins will also have cross-reactivity with cephalosporins. Thus, cephalosporin antibiotics are contraindicated in people with a history of allergic reactions (urticaria, anaphylaxis, interstitial nephritis, etc) to penicillins or cephalosporins.

Hematologic toxicity

  • Thrombocytopenia, neutropenia, abnormalities of platelet function and coagulation have been reported with certain cephalosporins.
  • Cephalosporin antibiotics are classed as Pregnancy category B.
Fluoroquinolones
  • Fluoroquinolones (fluoridated quinolones) are the newest class of antibiotics. Their generic name often contains the root “floxacin”. They are synthetic compounds and are not derived from bacteria.
  • The earliest first-generation medications are referred to as quinolones and newer generations as fluoroquinolones. The older quinolones are not well absorbed and are used to treat mostly urinary tract infections. The fluoroquinolones are broad-spectrum agents with excellent oral bioavailability. Because of their high absorption fluoroquinolones can be administered not only intravenously but orally as well.

Fluoroquinolones are used to treat urinary tract infections, skin infections, and respiratory infections (such as sinusitis, pneumonia, bronchitis), pulmonary infections in cystic fibrosis. Fluoroquinolones are bactericidal and kill bacteria by inhibiting bacterial enzyme DNA gyrase.

Fluoroquinolone family includes:

  • clinafloxacin
  • ciprofloxacin
  • gatifloxacin
  • levofloxacin
  • lomefloxacin
  • ofloxacin
  • sparfloxacin
  • trovafloxacin
Fluoroquinolones side effects
  • Fluoroquinolones are generally well tolerated and have an acceptable level of safety. The most common side effects include nausea, vomiting, diarrhea, abdominal pain. More serious but less common side effects are central nervous system disturbances (headache, confusion, dizziness, tremor), phototoxicity (more common with lomefloxacin and sparfloxacin), prolongation of the QT interval[rx], tendinopathy and tendon rupture, and convulsions.

Fluoroquinolones should be avoided when possible in pregnant women and children.

Tetracyclines
  • Tetracyclines are an old class of antibiotics. They got their name for their chemical structure which contains four hexagonal rings. Tetracyclines are derived from a species of Streptomyces bacteria.
  • Tetracycline antibiotics are bacteriostatic agents and work by inhibiting the bacterial protein synthesis via interaction with the 30S subunit of the bacterial ribosome. Tetracyclines are effective against a wide variety of microorganisms, including spirochetes, atypical bacteria, rickettsia, and amebic parasites.

Current applications of tetracyclines include treatment of peptic ulcer disease as part of a multi-drug regimen, infections of the respiratory tract, cholera, Rocky Mountain spotted fever, Lyme disease, typhus, prophylaxis of traveler’s diarrhea, malaria prophylaxis. Their most common current use is in the treatment of acne vulgaris and rosacea.

Tetracycline antibiotics are:

  • doxycycline
  • minocycline
  • oxytetracycline
  • tetracycline
Tetracyclines side effects
  • Common side effects associated with tetracyclines include stomach cramps, diarrhea, nausea, vomiting, esophageal ulceration, sore mouth or tongue. Tetracyclines can cause skin photosensitivity, which increases the risk of sunburn under exposure to UV light. This may be of particular importance for those intending to take on holidays long-term doxycycline as malaria prophylaxis.
  • Rarely, tetracyclines may cause allergic reactions. Very rarely severe headache and vision problems may be signs of dangerous secondary intracranial hypertension.
  • Tetracycline antibiotics should not be used in children under the age of 8, and specifically during periods of tooth development. Tetracyclines are classed as pregnancy category D. Tetracyclines may cause the gray to yellow discoloration of actively forming teeth and deposition in growing bones.
Macrolides
  • The macrolide antibiotics owe their name to a macrocyclic lactone ring in their chemical structure. They are derived from Streptomyces bacteria. The macrolides target bacterial ribosomes and prevent protein production and are mainly bacteriostatic agents.
  • Erythromycin, the prototype of this class, has a spectrum and use similar to penicillin. Newer members of the group, azithromycin, and clarithromycin, are particularly useful for their excellent lung penetration. Macrolide antibiotics are used to treat respiratory tract infections (such as pharyngitis, sinusitis, and bronchitis), genital, gastrointestinal tract, and skin infections.

Macrolide antibiotics are:

  • azithromycin
  • clarithromycin
  • dirithromycin
  • erythromycin
  • roxithromycin
  • troleandomycin
Macrolides side effects
  • Macrolides are usually tolerated quite well. Most common adverse effects include nausea, vomiting, abdominal discomfort, and diarrhea. They have been rarely associated with reversible deafness and allergic reactions (including angioedema, anaphylaxis, and dermatologic reactions). Oral erythromycin may be highly irritating to the stomach and when given by injection may cause severe thrombophlebitis. Macrolide antibiotics should be used with caution in patients with liver dysfunction.

Pregnancy category B – Azithromycin, erythromycin.
Pregnancy category C – Clarithromycin, dirithromycin, troleandomycin.

Aminoglycosides
  • Aminoglycosides are derived from various species of Streptomyces.
  • In 1943, Selman Waksman, together with his co-workers, discovered that a bacterium Streptomyces griseus produced an antibiotic substance which they named “streptomycin.” Selman Waksman was awarded the Nobel Prize in Physiology or Medicine in 1952 for his discovery of streptomycin.
  • The aminoglycosides are bactericidal and work by binding to the 30S subunit of the bacterial ribosome, thus stopping bacteria from making proteins.
  • Aminoglycoside antibiotics are used to treat infections caused by gram-negative bacteria. Aminoglycosides may be used in combination with penicillin or cephalosporins to ensure better antimicrobial coverage. Aminoglycosides work quite well, but bacteria can become resistant to them. Since aminoglycosides are broken down easily in the stomach, they can’t be given by mouth and must be injected. Generally, aminoglycosides are given for short time periods.

Aminoglycoside grope includes

  • amikacin
  • gentamicin
  • kanamycin
  • neomycin
  • streptomycin
  • tobramycin

List of Antibiotic Classes in details(Types of Antibiotics)

Most antibiotics fall into their individual antibiotic classes. An antibiotic class is a grouping of different drugs that have similar chemical and pharmacologic properties. Their chemical structures may look comparable, and drugs within the same class may kill the same or related bacteria.

However, it is important not to use an antibiotic for infection unless your doctor specifically prescribes it, even if it’s in the same class as another drug you were previously prescribed. Antibiotics are specific for the kind of bacteria they kill. Plus, you would need a full treatment regimen to effectively cure your infection, so don’t use or give away leftover antibiotics.rxharun.com/Antibiotic-OverviewAntibiotic Grouping By Mechanism

Cell Wall SynthesisPenicillins

  • Cephalosporins
  • Vancomycin
  • Beta-lactamase Inhibitors
  • Carbapenems
  • Aztreonam
  • Polymycin

BacitracinProtein Synthesis InhibitorsInhibit 30s Subunit

  • Aminoglycosides (gentamicin)
  • Tetracyclines

Inhibit 50s Subunit  Macrolides

  • Chloramphenicol
  • Clindamycin
  • Linezolid

StreptograminsDNA Synthesis InhibitorsFluoroquinolones
MetronidazoleRNA synthesis InhibitorsRifampinMycolic Acid synthesis inhibitorsIsoniazidFolic Acid synthesis inhibitors

  • Sulfonamides
  • Trimethoprim
Inhibits Cell Wall Synthesis
Penicillins
(bactericidal: blocks cross linking via competitive inhibition of the transpeptidase enzyme)

Class/MechanismDrugsIndications (**Drug of Choice)ToxicityPenicillinPenicillin G

  • Aqueous penicillin G
  • Procaine penicillin G
  • Benzathine penicillin G

Penicillin VStrep. pyogenes (Grp.A)

  • Step. agalactiae (Grp.B
  • C. perfringens(Bacilli)

Hypersensitivity reaction

  • Hemolytic anemia
  • Aminopenicillins
  • Ampicillin
  • AmoxicillinAbove +
    ↑ Gram-negative:
    E. faecalis**
    E. Coli

AbovePenicillinase-resistant-penicillins

  • Methicillin
  • Nafcillin
  • Oxacillin
  • Cloxacillin
  • DicloxacillinAbove +
    PCNase-producingStaph. aureusAbove +
    Interstitial nephritis

Antipseudomonal penicillins

  • Carbenicillin
  • Ticarcillin
  • PiperacillinAbove +Pseudomonas aeruginosa
Cephalosporins
(bactericidal: inhibits bacterial cell wall synthesis via competitive inhibition of the transpeptidase enzyme)

1st generation 

  • Cefazolin
  • CephalexinStaph. aureus** Staph. epidermidis**

Some Gram-negatives

  • E. Coli
  • Klebsiella
  • Allergic reaction
    Coombs-positive anemia (3%)

2nd generation

  • Cefoxitin
  • Cefaclor
  • CefuroximeAbove +↑ Gram-negativeAllergic Reaction
  • ETOH Disulfiram reaction

3rd generation

  • Ceftriaxone
  • Cefotaxime
  • Ceftazidime
  • Cefepime (4th generation)Above +
  • ↑ Gram-negative PseudomonasAllergic Reaction ETOH Disulfiram reaction
Other Cell Wall Inhibitors
  • Vancomycin 
    (bactericidal: disrupts peptioglycan cross-linkage)
  • VancomycinMRSA

Beta-lactamase Inhibitors 
(bactericidal: blocking cross linking)

  • Clavulanic Acid
  • Sulbactam
  • Tazobactam

Carbapenems

  • Imipenem (+ cilastatin)
  • Meropenem
  • Doripenem

Aztreonam

  • AztreonamGram-negative rods

Bacitracin

  • BacitracinTopical Gram-positive infections
Protein Synthesis Inhibition Anti-30S ribosomal subunit

Aminoglycosides
(bactericidal: irreversible binding to 30S)

  • Gentamicin
  • Neomycin
  • Amikacin
  • Tobramycin

Tetracyclines(bacteriostatic: blocks tRNA)Tetracycline

  • Doxycycline
  • Minocycline
  • DemeclocyclineRickettsia
Anti-50S ribosomal subunit

Macrolides
(bacteriostatic: reversibly binds 50S)

  • Erythromycin
  • Azithromycin
  • ClarithromycinStreptococcus

Chloramphenicol
(bacteriostatic)

  • Chloramphenicol
  • Gray Baby Syndrome

Lincosamide
(bacteriostatic: inhibits peptidyl transferase by interfering with amino acyl-tRNA complex)

  • ClindamycinBacteroides fragilis

Linezolid
(variable)

  • LinezolidResistant Gram-positives

Streptogramins

  • Quinupristin
  • DalfopristinVRE
  • GAS and S. aureus skin infections
DNA Synthesis Inhibitors
  • Fluoroquinolones (bactericidal: inhibit DNA gyrase enzyme, inhibiting DNA synthesis)

1st generation  

  • Nalidixic acidicity

2nd generation

  • Ciprofloxacin
  • Norfloxacin
  • Enoxacin
  • Ofloxacin
  • LevofloxacinAs Above +Pseudomonasas

3rd generation

  • GatifloxacinAs above + Gram-positives as above

4th generation

  • Moxifloxacin
  • GemifloxacinAs above + Gram-positives + anaerobesas above

Other DNA Inhibitors

Metronidazole

RNA Synthesis Inhibitors

Rifampin

Mycolic Acids Synthesis Inhibitors

Isoniazid

  • IsoniazidzTB
    Latent TB
Folic acid Synthesis Inhibitors

Trimethoprim/Sulfonamides

Gram Postive Cocci
Staphylococcus Staph. aureus
MSSA
MRSA
Staph. epidermis
Staph saprophyticus
Streptococcus Strep pneumoniae
Strep pyogenes (Group A)
Strep agalacticae (Group B)
Strep viridans
Strep Bovis (Group D)
Enterococci E. faecalis (Group D strep)
Gram Positive Bacilli
Spore Forming Bacillus anthracis
Bacillus cereus
Clostridium tetani
Clostridium botulinum
Clostridium perfringens
Clostridium difficile
Non-Spore Forming Corynebacterium diphtheriae
Listeria monocytogenes
Gram Negative Cocci
Neisseria Neisseria meningitidis
Neisseria gonorrhoeae
Gram Negative Bacilli
Enterics Escherichia coli
Salmonella typhi
Salmonella enteridis
Shigella dysenteriae
Klebsiella pneumoniae
Serratia
Proteus
Campylobacter jejuni
Vibrio cholerae
Vibrio parahaemolyticus/vulnificus
Helicobacter pylori
Pseudomonas aeruginosa
Bacteroides fragilis
Respiratory bacilli Haemophilus influenzae
Haemophilius ducreyi
Bordatella pertussis
Zoonotic bacilli Yersinia enterocolitica
Yersinia pestis
Brucella
Francisella tularensis
Pasteurella multocida
Bartonella henselae
Other Gardnerella vaginalis
Other Bacteria
Mycobacteria Mycobacterium tuberculosis
Mycobacterium leprae
MOTTS
Spirochetes Borrelia burgdorferi
Leptospira interrogans
Treponema pallidum
Chlamydiaceae Chlamydia trachomatis
Chlamydophila
Rickettsia
Ehrlichia
Mycoplasmataceae Mycoplasma pneumoniae
Ureaplasma urealyticum
Fungus-like Bacteria Actinomyces israelii
Nocardia

Penicillins

rxharun.com/Antibiotic-Overview

Another name for this class is the beta-lactam antibiotics, referring to their structural formula. The penicillin class contains five groups of antibiotics: aminopenicillins, antipseudomonal penicillins, beta-lactamase inhibitors, natural penicillins, and the penicillinase resistant penicillins. Common antibiotics in the penicillin class include:

  • penicillin V potassium
  • amoxicillin
  • amoxicillin/clavulanate (Augmentin)

Tetracyclines

Tetracyclines are broad-spectrum against many bacteria and treat conditions such as acne, urinary tract infections (UTIs), intestinal tract infections, eye infections, sexually transmitted diseases, periodontitis (gum disease), and other bacterial infections. The tetracycline class contains well-known drugs such as:

  • doxycycline
  • tetracycline
  • minocycline

Cephalosporins

There are five generations of cephalosporins, with increasing expanded coverage to include gram-negative infections. Cephalosporins treat many infections, including strep throat, ear infections, urinary tract infections, skin infections, and meningitis. The fifth generation cephalosporin ceftaroline (Teflaro) is active against methicillin-resistant Staphylococcus aureus (MRSA). You’ve probably heard of common medications in this class, like:

  • cefuroxime (Ceftin)
  • ceftriaxone (Rocephin)
  • Cefdinir (Omnicef)

Quinolones

The quinolones, also known as the fluoroquinolones, are a synthetic, bactericidal antibacterial class with a broad-spectrum of activity. The quinolones can be used for difficult-to-treat urinary tract infections when other options are aren’t effective, hospital-acquired pneumonia, bacterial prostatitis, and even anthrax or plague. The FDA issued a strong warning about this class in 2016. Familiar names in the fluoroquinolone class include:

  • ciprofloxacin (Cipro)
  • levofloxacin (Levaquin)
  • moxifloxacin (Avelox)

Lincomycins

This class has activity against gram-positive aerobes and anaerobes (bacteria that can live without oxygen), as well as some gram-negative anaerobes. The lincomycin derivatives may be used to treat serious infections like pelvic inflammatory disease, intra-abdominal infections, lower respiratory tract infections, and bone and joint infections. These drugs include:

  • clindamycin (Cleocin)
  • lincomycin (Lincocin)

Macrolides

The macrolides can be use to treat community-acquired pneumonia, pertussis (whooping cough), or for uncomplicated skin infections, among other susceptible infections. Ketolides are a newer generation of antibiotic developed to overcome macrolide bacterial resistance. Frequently prescribed macrolides are

Sulfonamides

Sulfonamides are effective against some gram-positive and many gram-negative bacteria, but resistance is widespread. Common uses for sulfonamides include UTIs, treatment or prevention of pneumocystis pneumonia, or ear infections (otitis media). Familiar names include:

  • sulfamethoxazole-trimethoprim
  • sulfasalazine
  • sulfisoxazole

Glycopeptide Antibiotics

Members of this group may be used for treating methicillin-resistant staphylococcus aureus (MRSA) infections, complicated skin infections, C. difficile-associated diarrhea, and enterococcal infections such as endocarditis which are resistant to beta-lactams and other antibiotics. Common drug names include:

  • dalbavancin
  • oritavancin
  • telavancin
  • vancomycin

Aminoglycosides

Aminoglycosides inhibit bacterial synthesis by binding to the 30S ribosome and act rapidly as bactericidal antibiotics (killing the bacteria). These drugs are usually given intravenously (in a vein through a needle). Common examples in this class are:

  • gentamicin
  • tobramycin
  • amikacin

Carbapenems

These injectable beta-lactam antibiotics have a wide spectrum of bacteria-killing power and may be used for moderate to life-threatening bacterial infections like stomach infections, types of pneumonia, kidney infections, multidrug-resistant hospital-acquired infections and many other types of serious bacterial illnesses. Members of this class include:

  • imipenem/cilastatin
  • meropenem
  • doripenem
  • ertapenem

Over the Counter Antibiotics

Over-the-counter (OTC) oral antibiotics are not approved in the U.S. A bacterial infection is best treated with a prescription antibiotic that is specific for the type of bacteria causing the infection. This will increase the chances that the infection is cured and help to prevent antibiotic resistance. In addition, a lab culture may need to be performed to pinpoint the bacteria and to help select the best antibiotic. Taking the wrong antibiotic — or not enough — may worsen the infection and prevent the antibiotic from working the next time.

There are a few OTC topical antibiotics that can be used on the skin. Some products treat or prevent minor cuts, scrapes or burn on the skin that may get infected with bacteria. These are available in creams, ointments, and even sprays.

Common OTC topical antibiotics

  • Neosporin, Medi-Quik (bacitracin/neomycin/polymyxin B)
  • Polysporin (bacitracin/polymyxin)
  • Triple antibiotic, generic (bacitracin/neomycin/polymyxin B)
  • Neosporin Plus (neomycin/polymyxin/pramoxine)

There are some OTC antibacterials for acne sufferers, too. They contain the antibacterial benzoyl peroxide, which also has mild drying effect for acne. Many products are found on the pharmacy shelves as gels, lotions, solutions, foams, cleaning pads, and even facial scrubs.

Common OTC antibacterials for acne

  • Clearskin
  • Oxy-10
  • Proactiv

Trending Antibiotic Articles

Patients frequently have questions about specific topics with antibiotics. Here are some articles that address common questions you may have about antibiotics.

  • Trying to make sense of the side effects noted on your antibiotic prescription medication guide? Read the Common Side Effects, Allergies and Reactions to Antibiotics article to understand the meanings.
  • Don’t understand what is meant by antibiotic resistance? Check out our Antibiotic Resistanceprimer and statistics on inappropriate antibiotic use.
  • Should you be concerned about taking Cipro
  • Wondering if you can still have that evening cocktail with your antibiotic? Scan the Antibiotics and Drinking Alcohol information to learn if you should skip it or not.
  • Think You’re Allergic to Penicillin? Maybe Not, Check out why here.
  • FDA clears the first test to help find antibiotic-resistant bacteria.

References

What Are The Most Common Side Effects of Antibiotics

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Lyme Disease; Causes, Symptoms, Diagnosis, Treatment

Lyme disease is the most common tick-borne disease in the United States. This review details the risk factors, clinical presentation, treatment, and prophylaxis for the disease. Typically, the tick must feed for at least 36 hours for transmission of the causative bacterium, Borrelia burgdorferi, to occur. Each of the 3 stages of the disease is associated with specific clinical features: early localized infection, with erythema migrans, fever, malaise, fatigue, headache, myalgias, and arthralgias; early disseminated infection (occurring days to weeks later), with neurologic, musculoskeletal, or cardiovascular symptoms and multiple erythema migrans lesions; and late disseminated infection, with intermittent swelling and pain of 1 or more joints (especially knees). Neurologic manifestations (neuropathy or encephalopathy) may occur. Diagnosis is usually made clinically. Treatment is accomplished with doxycycline or amoxicillin; cefuroxime axetil or erythromycin can be used as an alternative. Late or severe disease requires intravenous ceftriaxone or penicillin G. Single-dose doxycycline (200 mg orally) can be used as prophylaxis in selected patients. Preventive measures should be emphasized to patients to help reduce risk.[rx]

The National Institute for Health and Care Excellence’s guidelines describe the importance of early diagnosis and management of Lyme disease.

A tick on a person's skin

Source: Shutterstock.com

Lyme disease is a tick-borne infectious disease caused by the bacterium Borrelia burgdorferi. Infected ticks can transmit the disease when they bite a human

Lyme disease is a vector-borne zoonotic infection that is caused by different genospecies of Borrelia and transmitted by the bite of an infected tick[1]. Ticks are found throughout the UK, although most do not carry the infection, and thrive in moist, humid conditions — particularly woodland and moorland, and some urban parks and gardens[2]. If left untreated, Lyme disease can develop to late manifestations, affecting the joints, nervous system or the heart.

Healthcare professionals in highly endemic areas have a major role to play in raising awareness, particularly for people visiting from areas where Lyme disease is less common and so may be unaware of the risk. This article describes how pharmacists and their teams can recognise the signs and symptoms of Lyme disease, and provide advice about prevention and management.

Epidemiology

Lyme disease can occur anywhere in the UK; however, areas that have a higher risk include the south of England (including central London) and the Scottish Highlands[1]. Peak incidence occurs in June, with a smaller peak in September, owing to increased tick activity during the early summer and autumn months when outdoor activities can place people at increased risk of tick exposure and, therefore, tick bites. Some cases occur following travel abroad, as Lyme disease is more commonly reported in Europe (particularly Eastern Europe), Asia, and parts of the United States and Canada[3].

The incidence of Lyme disease is steadily increasing; however, the reasons for this are complex and may include climate change, changes in land management and biodiversity, and human interaction with nature, as well as increased awareness of the infection resulting in more cases being reported[4]. In 2017, 1,579 cases were recorded in England and Wales, an increase from 1,134 cases in 2016[3]. The most recent data for Scotland show that 200 cases were recorded during 2015[5]. However, these figures represent laboratory-confirmed cases and do not include data from clinically diagnosed cases, or those that may have been missed or misdiagnosed[6].

Risk factors

People of all ages and both sexes are equally susceptible to Lyme disease, although the highest rates occur in older adults aged 45–64 years[3]. Particular “at risk” groups can include people who take part in recreational outdoor pursuits (e.g. walkers, off-road cyclists, anglers and horse riders), school-aged children, and occupational groups, such as countryside officers, conservation officers and other outdoor workers[2].

Signs and symptoms

An important early sign of Lyme disease, found in around two-thirds of cases, is a slowly expanding annular skin rash called erythema migrans (EM). This may occur 1–4 weeks after a tick bite (with a range of 3 days to 3 months) and can last for several weeks. There is often an area of central clearing that gives the rash a “bull’s eye” appearance (see Figure 1), although atypical rashes that are bruise-like or homogenously red also occur.

Erythema migrans Lyme disease rash

Figure 1: Erythema migrans rash

Source: Alamy

A slowly expanding, ring-shaped (or “bull’s eye”) rash called erythema migrans is an important early sign of Lyme disease and is found in around two-thirds of cases

An EM rash is usually not hot, itchy, scaly or painful, which may distinguish it from other common skin conditions such as cellulitis, ringworm and insect bites[1]. A localised area of redness may occur as a reaction to a tick bite, but this usually resolves over 3–5 days and should be kept under review, rather than treated.

Patients who do not present with EM may be more difficult to diagnose and may receive a delayed or missed diagnosis[7]. These patients may present with several of the following non-specific symptoms:

  • Fatigue;
  • Malaise;
  • Headache;
  • Neck pain or stiffness;
  • Fever and sweats;
  • Mild cognitive impairment, such as memory problems and difficulty concentrating (referred to as ‘brain fog’);
  • Swollen glands;
  • Fleeting muscle and joint pains;
  • Paraesthesia.

The National Institute for Health and Care Excellence (NICE) guideline recommends that if there is a high clinical suspicion of Lyme disease in people without EM, the test for Lyme disease should be offered and treatment with antibiotics should be considered while waiting for the test results[1].

Pharmacists and healthcare professionals may be alerted to the possibility of Lyme disease by questioning the patient about:

  • The likelihood of tick exposure (e.g. exposure to highly endemic areas, recreational/occupational activities, seasonal factors);
  • History of the tick bite (these may go unnoticed);
  • EM;
  • Flu-like symptoms, especially following tick exposure, a tick bite or EM;
  • Other focal symptoms and signs consistent with Lyme disease, including:
    • Neurological symptoms (e.g. facial palsy, unexplained radiculitis [nerve root inflammation]);
    • Joint pain and swelling;
    • Meningitis, carditis and uveitis (although these are rare symptoms);
    • Chronic skin rashes.

Focal symptoms and signs may begin to appear in the first few weeks and months following infection and indicate that the infection has spread from the skin with organ involvement. In the UK and Europe, disseminated Lyme disease tends to cause neurological problems, whereas in the United States, a Lyme arthritis, usually involving a single large joint such as the knee or elbow, is more common[8].

Clinical manifestations of Lyme disease (,,)
Stage System Manifestation
Early localized disease (< 30 days)* Skin Erythema migrans (note: must be > 5 cm in diameter, painless and slowly expanding)
Systemic Fever
Arthralgias
A headache
Early disseminated disease (< 3 months)* Skin Multiple erythema migrans
Systemic Fever
Arthralgias
A headache
Lymphadenopathy
Heart Atrioventricular block
Tachyarrhythmias
Myopericarditis
Myocardial dysfunction
CNS Aseptic meningitis
Cranial neuropathy (especially facial nerve palsy)
Motor or sensory radiculopathy
Ocular Conjunctivitis (rare)
Late disseminated disease (> 3 months)* MSK Oligoarticular arthritis
CNS Encephalopathy
Axonal polyradiculoneuropathy
Chronic encephalomyelitis
Ocular Retinitis (rare)

* Note: While there may be exceptions, these time frames provide clinicians with a general guide on when the different manifestations tend to occur.
CNS = central nervous system.
MSK = musculoskeletal.

Diagnosis

Patients with erythema migrans

An important recommendation in the NICE guideline is that Lyme disease should be diagnosed clinically without laboratory testing in patients with EM[1]; EM is specific for Lyme disease and prompt treatment will prevent disease progression.

Patients without erythema migrans

However, NICE recommends using a combination of clinical presentation and laboratory testing to guide diagnosis and treatment in patients without EM.

Lyme serology testing (see Box 1) relies on detecting a measurable antibody response to the bacteria, which may be limited in the early stages of infection. Patients with impaired immunity (e.g. those taking immunosuppressants) may also have a false-negative result. The advice from NICE is not to rule out a diagnosis of Lyme disease if there is high clinical suspicion, despite negative test results. False-positive results may occur as a results of previous infection or a cross-reaction.

Box 1: Lyme serology testing

In the UK, Lyme serology testing involves two stages:

  • Stage 1: An enzyme immunoassay or an enzyme-linked immunosorbent assay (commonly known as ELISA) aimed at detecting antibodies to Borrelia spp.;
  • Stage 2: A second tier immunoblot to confirm that any antibodies present are specific to Borrelia spp.

The National Institute for Health and Care Excellence has produced an algorithm showing recommendations for testing of Lyme disease[9]. Tests should be carried out at laboratories that are accredited by the UK Accreditation Service, use validated tests and participate in a formal external quality assurance programme.

Histological examination of tissues (e.g. synovial fluid aspirate, synovial membrane, skin biopsies and lumbar puncture with cerebrospinal fluid analysis) may also be needed to confirm diagnosis. Polymerase chain reaction testing aimed at direct detection of Borrelia DNA in tissues may be requested via the Lyme reference laboratory, but has limited sensitivity owing to the low numbers of bacteria in tissues samples[10].

Differentials

Symptoms of Lyme disease may overlap with a range of other conditions, including other infectious diseases and tick-borne diseases, as well as a range of non-infectious neurological and auto-immune conditions. This includes but is not limited to[11]:

  • Multiple sclerosis;
  • Bell’s palsy;
  • Stroke;
  • Parkinson’s disease;
  • Guillain-Barré syndrome;
  • Systemic lupus erythematosus;
  • Sarcoidosis.

The relapsing remitting pattern of pain and fatigue may also resemble chronic fatigue syndrome[12].

Treatment of Lyme Disease

Treatment of Lyme Disease

Condition and Recommended Drug Dose Duration†days Comments
Erythema migrans
Doxycycline (for patients ≥8 yr of age) 200 mg/day (pediatric dose, 4 mg/kg/day) orally, divided into two doses per day 14 (range, 10–21) Do not use to treat children <8 yr of age or women who are pregnant or lactating; warn patient about exposure to sun, since photosensitivity rash occurs in 20–30% of patients; drug has good penetration into the central nervous system; patient should take drug with fluids to minimize nausea and gastrointestinal irritation; also effective against granulocytic anaplasmosis but not against babesiosis
Amoxicillin 1500 mg/day (pediatric dose, 50 mg/kg/day) orally, divided into three doses per day 14 (range, 14–21) This agent is not effective against granulocytic anaplasmosis or babesiosis
Cefuroxime axetil 1000 mg/day (pediatric dose, 30 mg/kg/day) orally, divided into two doses per day 14 (range, 14–21) This agent is not effective against granulocytic anaplasmosis or babesiosis
Meningitis§
Ceftriaxone 2 g/day (pediatric dose, 50–75 mg/kg/day) intravenously once per day 14 (range, 10–28) Treatment has risks associated with indwelling catheters, including infection, and can cause pseudolithiasis in the gallbladder
Cefotaxime 6 g/day (pediatric dose, 150– 200 mg/kg/day) intravenously, divided into doses administered every 8 hr 14 (range, 10–28) Treatment has risks associated with indwelling catheters, including infection
Cranial-nerve palsy without clinical evidence of meningitis
Doxycycline (for patients ≥8 yr of age) 200 mg/day (pediatric dose, 4 mg/kg/day) orally, divided into two doses per day 14 (range, 14–21)
Amoxicillin 1500 mg/day (pediatric dose, 50 mg/kg/day) orally, divided into three doses per day 14 (range, 14–21) See comments for drugs used to treat erythema migrans; there is not good evidence that treatment changes the outcome of facial palsy, but it does prevent additional sequelae of infection
Cefuroxime axetil 1000 mg/day (pediatric dose, 30 mg/kg/day) orally, divided into two doses per day 14 (range, 14–21)
Carditis
Same oral agents as for erythema migrans; same parenteral agents as for meningitis Same doses as for oral and parenteral agents used to treat erythema migrans 14 (range, 14–21) Patients who are symptomatic should be hospitalized, monitored, and treated initially with a parenteral agent such as ceftriaxone; some patients with advanced heart block require a temporary pacemaker; after advanced block resolves, treatment may be completed with an oral agent
Arthritis
Same oral agents as for erythema migrans; same parenteral agents as for meningitis Same doses as for oral and parenteral agents used to treat erythema migrans 28 Nonsteroidal anti-inflammatory agents are often helpful as adjunctive treatment; for patients in whom arthritis persists or recurs, most experts recommend a second 28-day course of oral treatment; 14–28 days of parenteral treatment is an alternative

*For each drug, the maximum pediatric dose is the adult dose.

†Recommendations are from the Infectious Diseases Society of America.
A ‡A reaction similar to the Jarisch–Herxheimer reaction may occur in the first 24 hours after treatment is begun.
§There is evidence from Europe that treatment of meningitis with doxycycline administered orally is as good as parenteral treatment, although the species of Borrelia that cause Lyme meningitis in Europe may be different from that in the United States.
Doxycycline is preferable because of its good penetration into the central nervous system.

Antibiotic treatment

Treatment with antibiotics should be prescribed according to symptom presentation and the second course of an alternative antibiotic should be considered for patients with ongoing symptoms[1]. If symptoms continue following two completed courses of antibiotics, healthcare professionals should discuss this with the appropriate national Lyme reference laboratory or refer the patient to a specialist.

However, it is important to note that NICE recommendations for antibiotic treatment have been chosen at the higher ranges of formulary doses and duration to reduce the risk of insufficient treatment. A Jarisch–Herxheimer reaction may occur between 1–12 hours after antibiotics are initiated, but can also occur later and last for a few hours or up to two days. Symptoms include a worsening of fever, chills, muscle pains and headache. If this occurs, patients should be advised to continue with antibiotic treatment and consult their doctor[1].

People aged 12 years and over

Patients who are diagnosed with Lyme disease without focal symptoms should be prescribed oral doxycycline 100mg twice per day or 200mg once per day for 21 days as first-line treatment[1]. For Lyme disease with focal symptoms, refer to Table 1 in the NICE guidance.

Children aged under 12 years

Children with Lyme disease, but no focal symptoms, who are aged 9–12 years and weigh less than 45kg should be prescribed oral doxycycline 5mg/kg in two divided doses on day one, followed by 2.5mg/kg daily in one or two divided doses for a total of 21 days as first-line treatment. For severe infections, this can be increased to 5mg/kg daily for 21 days[1].

Children under 9 years of age (who are 33kg and under) with Lyme disease, but without focal symptoms, should be prescribed oral amoxicillin 30mg/kg three times per day for 21 days[1].

For children with Lyme disease who have focal symptoms, refer to Table 2 in the NICE guidance (see Box 2).

The NICE committee acknowledged that although doxycycline is not licensed in the UK for children aged under 12 years — and is contraindicated in this age group because of side effects (such as teeth staining) — use in children aged 9 years and over is now accepted specialist practice. The committee agreed that doxycycline is the most effective treatment for Lyme disease and that the risk of dental problems in children is low when it is used for short-term treatment (28 days or less)[1],[13].

Pregnant women

Women who are pregnant should be treated with antibiotics that are appropriate for the stage of pregnancy in accordance with the British National Formulary[14]. Women who contract Lyme disease during pregnancy are unlikely to pass the infection on to their baby if they complete the full course of recommended antibiotics. However, if there are concerns about the baby, this should be discussed with a paediatric infectious disease specialist[1].

Ongoing treatment

It may take time for some patients to recover but their symptoms should gradually improve in the months after antibiotic treatment (see Box 2). However, patients whose diagnosis and treatment is delayed, and those with evidence of central nervous system involvement, may experience debilitating ongoing symptoms[15],[16]. The cause of these symptoms is not fully understood and may include tissue damage, post-infectious immune dysfunction and persistence of bacteria or bacterial debris[16].

NICE recommends offering regular clinical review and reassessment to patients with ongoing symptoms, including patients with no confirmed diagnosis. Symptoms related to Lyme disease that may need assessment and management, with reference to relevant NICE guidelines, include:

  • Chronic pain;
  • Depression and anxiety;
  • Fatigue;
  • Sleep disturbance.

Prophylactic treatment

The NICE guideline does not cover prophylactic treatment and there is no vaccine currently licensed for use in humans.

Prophylactic treatment following a tick bite with a single dose of antibiotics (e.g. doxycycline) is used in the United States but is not recommended in Europe because the risk of Lyme disease following a single tick bite is low[17],[18].

Box 2: Case study

A seven-year-old boy was seen by his GP a week after returning from a camping holiday in the Scottish Highlands. He had a 5cm annular rash at the back of his neck but was otherwise well. His mother had not noticed a tick bite.

The GP diagnosed erythema migrans and prescribed a seven-day course of amoxicillin at the lower end of the British National Formulary dose range. Two weeks later, the child developed facial palsy, headache and was lethargic.

The GP contacted a paediatric neurologist who arranged for admission and diagnosed Lyme neuroborreliosis, confirmed by Lyme serology and lumbar puncture. The child was showing signs of meningitis and was therefore treated with intravenous ceftriaxone 80mg/kg daily for 21 days. Recovery happened slowly over a six-month period.

Role of the pharmacist

Pharmacists and other healthcare professionals, particularly those in high-risk geographical areas, can provide advice about ticks, tick bites and the risk of Lyme disease[1],[2],[19], including:

Prevention

  • Advice on the areas where ticks are usually found (i.e. woodland and moorland);
  • How people can avoid tick bites by covering exposed skin (i.e. wearing trousers rather than shorts), keeping to defined paths when outdoors and using insect repellents containing DEET or permethrin;

Checking for ticks

  • How people can check themselves and their children for ticks after possible exposure;
  • How to properly brush down clothing before going inside;

Tick removal

  • The importance of prompt tick removal — the longer an infected tick remains attached to the skin, the higher the risk of Lyme disease transmission;
  • How to remove ticks correctly — especially if the pharmacy stocks tick removal tools, such as tick cards or tick hooks (see Box 3 and Figure 2);
  • How to clean the bite site with antiseptic and watch for signs of a rash;

Reassurance

  • People may ask whether all tick bites cause Lyme disease:
    • Advise that not all ticks are infected;
    • Advise that the infection rate varies from 0–15%[20].

Box 3: How to remove ticks correctly

When dealing with a tick, the main aims are to remove the tick promptly, to remove all parts of the tick’s head and body, and to prevent it from releasing additional saliva or regurgitating its stomach contents into the bite wound. The risk of infection increases the longer a tick remains attached to the skin.

Do:

  • Use an approved tick removal tool (available from Lyme Disease Action or many vets and pet shops), and follow the instructions provided. There are two common types of removal tools available — the hook and the loop — that are designed to be twisted to facilitate removal (see Figure 2). These tools will grip the head of the tick without squashing the body;
  • Use alternative methods if the tick removal tools are not available:
    • With pointed tweezers (not blunt eyebrow tweezers) grasp the tick as close to the skin as possible. Without squeezing the tick’s body, pull the tick out without twisting (it is difficult to twist tweezers without separating the tick’s head from its body). There may be considerable resistance;
    • If no tools are available, use a fine thread (e.g. cotton or dental floss). Tie a single loop of thread around the tick’s mouthparts, as close to the skin as possible, then pull upwards and outwards without twisting;
  • Start by cleansing the tweezers/tool with antiseptic. After tick removal, cleanse the bite site and the tool with antiseptic;
  • Wash hands thoroughly afterwards;
  • Keep the tick in a sealed container in case a doctor asks for evidence (label it with date and location). Public Health England is also currently running a tick surveillance scheme to record tick distributions on a national scale (ticks can be posted to them as per instructions on their website).

Do not:

  • Squeeze the body of the tick, as this may cause the head and body to separate, leaving the head embedded in the skin;
  • Use your fingernails to remove a tick. Infection can occur via any breaks in the skin (e.g. close to the fingernail);
  • Crush the tick’s body, as this may cause it to regurgitate its infected stomach contents into the bite wound;
  • Try to burn the tick off, apply petroleum jelly, nail polish or any other chemical. Any of these methods can cause discomfort to the tick, resulting in regurgitation, or saliva release.

Source: Lyme Disease Action[20]

tick hooks

Figure 2: How to safely remove a tick

Source: JL/ The Pharmaceutical Journal

Two common tick removal tools. A) The hook. Approach the tick from the side until it is held by the hook and lift the hook very lightly and turn it to remove the tick. B) The loop. Release the lasso and carefully pass the loop over the tick against the skin. Tighten the loop, rotate and pull the tick out vertically.

Pharmacists should be vigilant for patients presenting with EM over the summer months and for patients with flu-like symptoms at a time when seasonal flu is receding. Such patients should be advised to seek medical help as soon as possible.

Patients with Lyme disease may seek help from the pharmacist for neurological symptoms, joint pain and swelling, multiple rashes, and cardiac or ophthalmic complications, although this is less common. The NICE guideline recommends a discussion with an appropriate specialist for any adult presenting in this way and an emergency referral if there is evidence of central nervous system involvement, cardiac involvement or uveitis. Diagnosis and management of Lyme disease in all people aged under 18 years should be discussed with a specialist, unless they have a single EM lesion and no other symptoms[1].

Useful resources

References

[1] National Institute for Health and Care Excellence. Lyme disease. NICE guideline [NG95]. 2018. Available at: https://www.nice.org.uk/guidance/ng95 (accessed October 2018)

https://www.ncbi.nlm.nih.gov/pubmed/18452688

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864449/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487875/

[2] Public Health England. ‘Be tick aware’ — toolkit for raising awareness of the potential risk posed by ticks and tick-borne disease in England. 2018. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/694157/PHE_Tick_Awareness_Toolkit.PDF(accessed October 2018)

[3] Public Health England. Lyme disease epidemiology and surveillance. 2018. Available at: https://www.gov.uk/government/publications/lyme-borreliosis-epidemiology/lyme-borreliosis-epidemiology-and-surveillance (accessed October 2018)

[4] Medlock JM & Leach SA. Effect of climate change on vector-borne disease risk in the UK. Lancet Infect Dis 2015;15(6):721–730. doi: 10.1016/S1473-3099(15)70091-5

[5] Health Protection Scotland & NHS National Services Scotland. Lyme disease, Scotland: annual totals as at 28 July 2016. 2016. Available at: http://www.hps.scot.nhs.uk/resourcedocument.aspx?id=5469 (accessed October 2018)

[6] Evans R, Mavin S, Holden S et al. Lack of accurate information on the prevalence of Lyme disease in the UK. BMJ 2014;348:g2037. doi.org/10.1136/bmj.g2037

[7] Aucott JN, Morrison C, Munoz B et al. Diagnostic challenges of early Lyme disease: lessons from a community case series. BMC Infect Dis 2009;9:79. doi: 10.1186/1471-2334-9-79

[8] Stanek G, Wormser GP, Gray J & Strle F. Lyme borreliosis. Lancet 2012;379(9814):461–473. doi: 10.1016/S0140-6736(11)60103-7

[9] National Institute for Health and Care Excellence. Lyme disease: laboratory investigations and diagnosis chart. 2018. Available at: https://www.nice.org.uk/guidance/ng95/resources/visual-summary-pdf-4792272301 (accessed October 2018)

[10] Dessau RB, van Dam AP, Fingerle V et al. To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis: a position paper of ESGBOR, the ESCMID study group for Lyme borreliosis. Clin Microbiol Infect 2018;24(2):118–124. doi: 10.1016/j.cmi.2017.08.025

[11] Mygland A, Ljøstad U, Fingerle V et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 2010;17(1):8–e4. doi: 10.1111/j.1468-1331.2009.02862.x

[12] Treib J, Grauer MT, Haass A et al. Chronic fatigue syndrome in patients with Lyme borreliosis. Eur Neurol 2000;43(2):107–109. doi: 10.1159/000008144

[13] Cross R, Ling C, Day NPJ et al. Revisiting doxycycline in pregnancy and early childhood — time to rebuild its reputation? Expert Opin Drug Saf 2016;15(3):367–382. doi: 10.1517/14740338.2016.1133584

[14] Pharmaceutical Press. British National Formulary 76. 2018. Available at: https://bnf.nice.org.uk/ (accessed October 2018)

[15] Eikeland R, Mygland Å, Herlofson K & Ljøstad U. European neuroborreliosis: quality of life 30 months after treatment. Acta Neurol Scand 2011;124(5):349–354. doi: 10.1111/j.1600-0404.2010.01482.x

[16] Rebman AW, Bechtold KT, Yang T et al. The clinical, symptom, and quality-of-life characterization of a well-defined group of patients with posttreatment lyme disease syndrome. Front Med 2017;4:224. doi: 10.3389/fmed.2017.00224

[17] Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43(9):1089–1134. doi: 10.1086/508667

[18] Tijsse-Klasen E, Jacobs JJ, Swart A et al. Small risk of developing symptomatic tick-borne diseases following a tick bite in The Netherlands. Parasit Vectors 2011;4(1):17. doi: 10.1186/1756-3305-4-17

[19] Piesman J, Mather TN, Sinsky RJ & Spielman A. Duration of tick attachment and Borrelia burgdorferi transmission. J Clin Microbiol 1987;25(3):557–558. PMID: 3571459

[20] Lyme Disease Action. 2017. Available at: https://www.lymediseaseaction.org.uk (accessed October 2018)

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Asthma Latest Research

Asthma Latest Research; Testing annual asthma reviews

Asthma Latest Research is a chronic lung disease that inflames and narrows the airways. Asthma causes recurring periods of wheezing (a whistling sound when you breathe), chest tightness, shortness of breath, and coughing. The coughing often occurs at night or early in the morning.

Asthma affects people of all ages, but it most often starts during childhood. In the United States, more than 25 million people are known to have asthma. About 7 million of these people are children.

Asthma Latest Research

Common signs and symptoms of asthma include:

  • Coughing. Coughing from asthma often is worse at night or early in the morning, making it hard to sleep.
  • Wheezing. Wheezing is a whistling or squeaky sound that occurs when you breathe.
  • Chest tightness. This may feel like something is squeezing or sitting on your chest.
  • Shortness of breath. Some people who have asthma say they can’t catch their breath or they feel out of breath. You may feel like you can’t get air out of your lungs.

Asthma Latest Researchl

Not all people who have asthma have these symptoms. Likewise, having these symptoms doesn’t always mean that you have asthma. The best way to diagnose asthma for certain is to use a lung function test, a medical history (including type and frequency of symptoms), and a physical exam.

The types of asthma symptoms you have, how often they occur, and how severe they are may vary over time. Sometimes your symptoms may just annoy you. Other times, they may be troublesome enough to limit your daily routine.

Severe symptoms can be fatal. It’s important to treat symptoms when you first notice them so they don’t become severe.

With proper treatment, most people who have asthma can expect to have few, if any, symptoms either during the day or at night.

Asthma Latest Researchl

Causes Asthma Symptoms To Occur for Asthma Latest Research

Many things can trigger or worsen asthma symptoms. Your doctor will help you find out which things (sometimes called triggers) may cause your asthma to flare up if you come in contact with them. Triggers may include:

  • Allergens from dust, animal fur, cockroaches, mold, and pollens from trees, grasses, and flowers
  • Irritants such as cigarette smoke, air pollution, chemicals or dust in the workplace, compounds in home décor products, and sprays (such as hairspray)
  • Medicines such as aspirin or other nonsteroidal anti-inflammatory drugs and nonselective beta-blockers
  • Sulfites in foods and drinks
  • Viral upper respiratory infections, such as colds
  • Physical activity, including exercise

Other health conditions can make asthma harder to manage. Examples of these conditions include a runny nose, sinus infections, reflux disease, psychological stress, and sleep apnea. These conditions need treatment as part of an overall asthma care plan.

Asthma Latest Researchl

Asthma is different for each person. Some of the triggers listed above may not affect you. Other triggers that do affect you may not be on the list. Talk with your doctor about the things that seem to make your asthma worse.

Your primary care doctor will diagnose asthma based on your medical and family histories, a physical exam, and test results.

Your doctor also will figure out the severity of your asthma—that is, whether it’s intermittent, mild, moderate, or severe. The level of severity will determine what treatment you’ll start on.

You may need to see an asthma specialist if:

  • You need special tests to help diagnose asthma
  • You’ve had a life-threatening asthma attack
  • You need more than one kind of medicine or higher doses of medicine to control your asthma, or if you have overall problems getting your asthma well controlled
  • You’re thinking about getting allergy treatments

Medical and Family Histories for Asthma Latest Research

Your doctor may ask about your family history of asthma and allergies. He or she also may ask whether you have asthma symptoms and when and how often they occur.

Let your doctor know whether your symptoms seem to happen only during certain times of the year or in certain places, or if they get worse at night.

Your doctor also may want to know what factors seem to trigger your symptoms or worsen them. For more information about possible asthma triggers, go to “What Are the Signs and Symptoms of Asthma?”

Your doctor may ask you about related health conditions that can interfere with asthma management. These conditions include a runny nose, sinus infections, reflux disease, psychological stress, and sleep apnea.

Diagnostic Tests for Asthma Latest Research

Fulmonary Function Test

Your doctor will use pulmonary function tests to check how your lungs are working.

  • Spirometry – measures how much air you can breathe in and out. It also measures how fast you can blow air out.
  • Bronchoprovocation tests – measure how your airways react to specific exposures. Using spirometry, this test repeatedly measures your lung function during physical activity or after you receive increasing doses of cold air or a special chemical to breathe in. Fractional concentration of exhaled nitric oxide tests measure how much nitric oxide is in the air you exhale. This test can be helpful to diagnose or guide asthma treatment in some patients.

Your doctor also may give you medicine and then test you again to see whether the results have improved.

If the starting results are lower than normal and improve with the medicine, and if your medical history shows a pattern of asthma symptoms, your diagnosis will likely be asthma.

OTHER TESTS

Your doctor may recommend other tests if he or she needs more information to make a diagnosis. Other tests may include:

  • Allergy testing to find out which allergens affect you, if any.
  • A test to measure how sensitive your airways are. This is called a bronchoprovocation (brong-KO-prav-eh-KA-shun) test. Using spirometry, this test repeatedly measures your lung function during physical activity or after you receive increasing doses of cold air or a special chemical to breathe in.
  • A test to show whether you have another condition with the same symptoms as asthma, such as reflux disease, vocal cord dysfunction, or sleep apnea.
  • A chest X-ray or an EKG (electrocardiogram). These tests will help find out whether a foreign object or other disease may be causing your symptoms.

Diagnosing Asthma in Young Children

Most children who have asthma develop their first symptoms before 5 years of age. However, asthma in young children (aged 0 to 5 years) can be hard to diagnose.

Sometimes it’s hard to tell whether a child has asthma or another childhood condition. This is because the symptoms of asthma also occur with other conditions.

Also, many young children who wheeze when they get colds or respiratory infections don’t go on to have asthma after they’re 6 years old.

A child may wheeze because he or she has small airways that become even narrower during colds or respiratory infections. The airways grow as the child grows older, so wheezing no longer occurs when the child gets colds.

A young child who has frequent wheezing with colds or respiratory infections is more likely to have asthma if:

  • One or both parents have asthma
  • The child has signs of allergies, including the allergic skin condition eczema
  • The child has allergic reactions to pollens or other airborne allergens
  • The child wheezes even when he or she doesn’t have a cold or other infection

The most certain way to diagnose asthma is with a pulmonary function test (spirometry), a medical history, and a physical exam. However, it’s hard to do pulmonary function tests in children younger than 5 years. Thus, doctors must rely on children’s medical histories, signs and symptoms, and physical exams to make a diagnosis.

Doctors also may use a four- to six-week trial of asthma medicines to see how well a child responds.

Testing annual asthma reviews for those who fail to attend

Abstract

Introduction: Suboptimal asthma care is related to increased morbidity and mortality. As a result, GP surgeries provide annual reviews for people with asthma. A high proportion of asthma patients do not attend their review but still collect asthma treatment from their community pharmacy. The aim of this proof-of-concept study was to evaluate the provision of patient non-attendance lists to community pharmacies who subsequently offered the review

Method: Five GP surgeries and ten community pharmacies were recruited in the east of England. Non-attender details were provided to community pharmacies from GP surgeries directly over a six-month period. Asthma reviews, funded by the medicines use review scheme, were delivered using standardised methodological approaches and electronic recording systems. Relevant routinely collected data were obtained before and after service provision. Stakeholder meetings were held to obtain feedback after service completion.

Results: A total of 27 patients received the service, with data collected on 26 patients. High levels of satisfaction with the service were identified. Pharmacist training, pharmacy accessibility and pharmacist competence were seen as service enablers. The pharmacy consultation room, GP surgery organisation and different IT systems were seen as barriers. A high level of satisfaction was identified, with the recommendation that the service should be offered to all patients with asthma irrespective of attendance.

Discussion and conclusion: This service model, which involved integrated working between GPs and community pharmacies and enabled asthma review non-attenders to be targeted, is in line with the recommendations of the Murray Review. Stakeholders recommended that community pharmacists should provide yearly asthma reviews and that these should be performed in close collaboration with GP surgeries.

Keywords: Asthma; asthma review; community pharmacy; GP referral; medicines use review; MUR; pharmacists.
Original submitted: 5 February 2018; Revised submitted: 29 May 2018; Accepted for publication: 25 June 2018; Published (online):

Asthma reviews should be offered when patients collect their asthma treatment from their community pharmacy.

Key points

  • The community pharmacy asthma review service (CPARS) widens patient choice and enables patients who usually do not attend at the GP surgery to receive an asthma review.
  • Patients, pharmacists and GP surgery staff all reported a high level of satisfaction with CPARS.
  • Pharmacists need to undertake additional training to enable them to provide asthma reviews at a standardised level.
  • CPARS encourages GP surgeries and community pharmacies to work together.

Introduction

Around 5.4 million people in the UK receive treatment for asthma, costing the NHS more than £1bn per year and resulting in 1.1 million lost working days. In addition, 70% of asthma-related accident and emergency (A&E) visits and hospital admissions and 90% of asthma-related deaths are believed to be preventable with appropriate treatment and monitoring. The 2015 National Review of Asthma Deaths (NRAD) found that the number of deaths per year caused by asthma remained at 1,200. Patients from lower socioeconomic groups are also less likely to have their asthma under control than patients from higher socioeconomic groups and, consequently, asthma has more of a negative effect on their usual daily activities.

The National Institute for Health and Care Excellence recommends that all patients with asthma receive a structured review at least annually. The review should monitor how well the patient’s condition is controlled, and ensure that they continue to be prescribed the most effective treatment and are supported to use their therapy appropriately. The review should include provision of a written personalised action plan, an asthma control assessment and specific training in inhaler technique.

However, around 30% of asthma patients fail to attend their asthma review for many reasons, including not believing their asthma warranted a review and forgetting to attend. Prescriptions for asthma treatment continue to be collected through community pharmacies and this provides an opportunity for the asthma review to be offered when patients collect their asthma therapy. Offering additional services while patients access another health service is known to result in greater service uptake than requests for patients to receive a service via an additional appointment. With patients reporting a preference for services that have been authorised by their GP, offering patients their asthma review at the point of prescription collection in the knowledge that this has been recommended by their GP should encourage service uptake.

The use of community pharmacists to successfully identify and manage asthma has been widely reported in international literature. In the UK, several studies have demonstrated wide acceptance for, and the potential value of, community pharmacists providing medicines-related asthma and respiratory services to patients. However, none of the reported services have been delivered in close cooperation with GP surgeries, whereby patients who fail to attend their yearly review are approached by their community pharmacist.

Community pharmacists in the UK are currently remunerated to provide advice on medicines use to patients with asthma through the national medicines use review (MUR) scheme; this model has been used in both the UK and Italy to enhance the care of patients with asthma. One large-scale UK study identified that the service could be enhanced if GPs were encouraged to refer patients to the service. Latif et al. identified that the lack of collaboration between community pharmacists and GPs surrounding the delivery of MURs is a lost opportunity to enhance patient care. The consequence of community pharmacists offering the service to patients without referral from their GP is the potential for duplication of effort. Within the main UK asthma MUR service evaluation, 70% of reviews provided by community pharmacists were for patients who had already received an asthma review from their GP surgery in the previous year.

The recent review of clinical pharmacy services in the UK recommends that the existing MUR element of the pharmacy contract should be redesigned to support the management of long-term conditions; this should be better integrated with GP surgeries to ensure that patients who are most in need are identified and that services are more efficiently delivered.

Concerns regarding large numbers of unnecessary asthma-related hospitalisations to James Paget University Hospital in Great Yarmouth, UK, led the hospital, Great Yarmouth and Waveney Clinical Commissioning Group, the local pharmaceutical committees (LPCs), the Centre for Pharmacy Postgraduate Education and the University of East Anglia to collectively develop a community pharmacy asthma review service (CPARS) for GP surgery non-attenders. This was delivered through the existing MUR service, with additional funding provided to cover the costs of involvement and data collection.

The widespread location of community pharmacies, combined with their opening hours being outside usual office hours, was seen as an opportunity to reach deprived areas and encourage attendance for those employed in roles with limited flexibility. Consequently, increasing access to asthma reviews through community pharmacies has the additional potential of reducing the known health inequalities in asthma management. The aim of this proof-of-concept study was to evaluate the service for acceptability and future refinement.

Method

The University of East Anglia Faculty of Medicine and Health Ethics Committee deemed the project to be a service evaluation.

A total of five GP surgeries and their ten associated community pharmacies were recruited within the Great Yarmouth and Lowestoft area. Patients who had not received an asthma review in the previous 12 months were identified and their community pharmacist informed of the need to review the patient, with their consent, when they presented for a prescription. GP surgeries decided which patient names were provided to the pharmacies; no specific exclusion criteria were set.

Pharmacist training

Fifteen pharmacists from ten community pharmacies attended six hours of training, divided over two evenings. Each pharmacy was also provided with a support pack to aid the review process. A summary of the training and support pack is provided in Box 1.

Box 1: Pharmacist training content and support pack

Pharmacist training

  • Project introduction;
  • Inhaler technique and asthma management;
  • Workshop session using In-Check™ (Alliance) device, peak flow meters and placebo inhalers;
  • Expert overview on asthma service delivery;
  • Role play with actors to undertake asthma review with formative feedback;
  • Clinical case studies;
  • The SIMPLE (stop smoking, inhaler technique, monitoring, pharmacotherapy, lifestyle and education) approach to the management of asthma.

Support pack content

  • In-Check Dial and disposable (white) mouthpieces;
  • Airzone™ (Alliance) standard peak flow meter and disposable mouthpieces (red);
  • Space chamber compact spacer device;
  • Placebo inhalers (relievers and preventers):

—Ellipta® (GlaxoSmithKline);

—Respimat® (Boehringer);

—Nexthaler® (Chiesi);

— Easyhaler® (Orion);

— DuoResp® Spiromax® (Teva Pharma);

— Metered dose inhaler (Fostair® [Chiesi]/ Ventolin™ [GlaxoSmithKline]/ Clenil® [Chiesi]);

— Turbohaler® (AstraZeneca);

— Genuair® (AstraZeneca).

  • Training devices:

—Ellipta training device;

—Turbohaler training whistles.

  • Asthma support pack (peak flow diary and blank asthma management plan in A5 wallet);
  • Steroid cards for patients receiving high dose inhaled corticosteroids;
  • Summary of British Thoracic Society treatment guidelines with current clinical commissioning group prescribing guidelines;
  • Information for patients: Staying in control of asthma.

Service design

From March 2017, the GP surgeries identified adult patients who had failed to attend their annual asthma review. Their names were provided to the participating community pharmacies and these patients were offered an annual review when they presented for their prescription. The review was arranged for a mutually convenient time. Figure 1 provides a summary of the service.

Asthma Latest ResearchlFlow chart showing the service design

Figure 1: Summary of service design

From March 2017, the GP surgeries identified adult patients who had failed to attend their annual asthma review. These patients were offered another review when they presented for their prescription, arranged for a mutually convenient time

Intervention delivery

The design and content of the asthma review was agreed by the lead respiratory nurse from James Paget University Hospital and the chief officer of Suffolk LPC, and this was used to develop the PharmOutcomes® (Pinnacle Health Partnership) — a national web-based community pharmacy intervention recording system. In addition to the standard MUR questions, the information that was assessed/discussed and subsequently collected using PharmOutcomes is provided in Box 2.

The PharmOutcomes system enables an email confirmation to be sent to the patient’s GP surgery when they have had an asthma review. This information allows the GP surgery to claim their quality and outcomes framework (QOF) points[19].

Pharmacy contractors received their MUR fee for each asthma review delivered plus a fee of £15 for completing PharmOutcomes during the process. They were paid £175 for each pharmacist that attended both training sessions, which equated to six hours of learning.

Box 2: Asthma review content recorded via Pharma Outcomes

  • Asthma Control Test;
  • Number of asthma-related attendances at accident and emergency in the past 12 months;
  • Smoking status assessment and offer of cessation service where appropriate;
  • Asthma trigger factors and plans for management;
  • Presence of symptoms of uncontrolled rhinitis;
  • Flu vaccination status and offer of flu vaccination where appropriate;
  • Adherence to current prescribed asthma medication;
  • Use of spacer for metered dose device;
  • Assessment of inhaler technique using in-check dial and associated intervention(s);
  • Measurement of peak expiratory flow rate and access to a peak flow meter;
  • Dose of inhaled corticosteroid and whether step-down therapy could be considered;
  • Need for a steroid card;
  • Identification of presence of an asthma management plan and associated intervention.

Data collection

The following quantitative and qualitative data were collected:

  • Content of pharmacist reviews;
  • Patient satisfaction;
  • Routine asthma-related data;
  • Stakeholder feedback;
  • Pharmacist review content collected via PharmOutcomes (summarised in Box 2).

Patients were asked for their preference on the mode of delivery of a service evaluation patient satisfaction questionnaire (i.e. postal or online) and sent the survey one month after service delivery. Along with an open question to allow for qualitative comments about the service, the questionnaire included questions regarding:

  • Their demographics;
  • The community pharmacy where the service was delivered;
  • The asthma control test;
  • Their satisfaction with the consultation;
  • Their willingness to receive the asthma review via this route in the future;
  • Whether they would recommend the review to others;
  • What they had changed as a result of the service.

The following data were collated by GP surgeries and provided in an anonymous format for evaluation purposes, and included all patients who received the asthma service through their community pharmacy for three months before and three months after service delivery:

  • Unplanned asthma-related hospitalisations;
  • Unplanned asthma-related GP visits;
  • Preventer inhaler use;
  • Reliever inhaler use.

Patients, GP surgery staff and pharmacists involved in the delivery of the service were invited to stakeholder meetings with the project research associate (non-pharmacist) to obtain feedback on the service. Two patient and public involvement members of the management team supported the patient stakeholder meeting and were not recorded as participants. All of the patient and pharmacist participants were independent of the project team. Two GP surgery staff who attended were seconded to the project team after the original grant had been submitted and were employed by the GP surgery that held the project grant.

Only one patient who completed the survey offered to attend a stakeholder feedback meeting. Therefore, the main GP surgery wrote to their ‘usual’ non-attenders to invite them in to identify why they do not attend and their views on offering the service through community pharmacy. Meetings were arranged at suitable times and locations, with food and remuneration for attendance provided.

The questions asked included:

  • What were your thoughts about community pharmacists providing asthma reviews?;
  • Which elements helped/hindered the delivery of the service?;
  • What was the effect of the service on your role?;
  • How could the service be upscaled/expanded?;
  • What are your thoughts on pharmacist training and support? (Pharmacist stakeholder meeting only);
  • How could the GP practice help you to attend your annual asthma review? (Patient stakeholder meeting only);
  • What barriers prevented you from attending your annual asthma review appointment? (Patient stakeholder meeting only).

Consent to record the meetings was obtained and notes were taken by a second member of the team. Two patient and public involvement panel group members assisted with the patient stakeholder meeting. The recordings were transcribed or listened to in order to check the notes for accuracy. Identified barriers, enablers and solutions were extracted by two members of the management team. Patient and public involvement members of the management team also reviewed the patient stakeholder meeting transcriptions.

Results

A total of 27 patients received the service from six different community pharmacies.

Pharmacist review content

Box 3 provides a summary of the reviews and the outcomes arising from them. The community pharmacists adhered to the requirements for service delivery and, in most cases, asthma inhaler technique was addressed during the review.

Box 3: Summary of service delivery using the SIMPLE model

Smoking cessation

  • All patients were asked about smoking status;
  • 11.1% of service recipients were smokers;

o All smokers were offered and declined smoking cessation.

Inhaler technique

  • All patients had their inhaler technique assessed;
  • 64.5% of patients were identified as having either an inappropriate technique or inhaler;
  • All patients with inappropriate inhaler devices were referred back to their GP surgery;
  • Counselling addressed inhaler technique in all remaining cases.

Monitoring

  • All patients completed the asthma control test;

o 55.6% of patients had controlled asthma;

  • 44.4% of patients had a peak expiratory flow rate (PEFR) of 80% or more of their predicted PEFR;
  • 40.7% of patients had a peak flow meter at home to enable self-monitoring.

Pharmacotherapy

  • 18.5% of patients had more than three short-acting beta agonists (relievers) in six months;
  • 7.4% of patients considered for a reduction in the dose of their inhaled corticosteroid (preventer);
  • 11.1% of patients required a spacer device for their inhaler.

Lifestyle

  • All patients were questioned about asthma triggers and plans to manage these triggers.

Education

  • All patients were asked about their asthma management plan;
  • 51.9% of patients were referred to obtain a plan from their GP or asthma nurse.

Patient satisfaction

In total, seven female patients completed the survey; three were aged 31–50 years, three were aged 51–65 years and one was aged over 65 years. Responses came from patients who had received the service from one of four different community pharmacies.

  • Six patients rated their asthma as ‘well controlled’ and one patient rated their asthma as ‘completely controlled’;
  • All patients agreed that they were satisfied with the information provided during the consultation;
  • All patients would have their review at the pharmacy again;
  • Six patients would recommend the service to others, while one patient was unsure;
  • Three comments were made regarding the unsuitability of the consultation rooms;
  • Two patients reported a better inhaler technique;
  • One patient reported taking their preventer inhaler more often;
  • One patient reported monitoring their condition more carefully.

Asthma-related data collection

Data were collected for 26 patients. There were six recorded unplanned asthma-related visits to the GP from six patients in the three months prior to the service and ten recorded unplanned asthma-related visits to the GP in the three months after, with four visits by one patient. There were no unplanned hospitalisations caused by asthma recorded before or after CPARS.

Stakeholder meetings

GP surgery staff

Five medical staff from three different GP surgeries attended. They identified community pharmacists not having access to patient notes as a barrier to effective service delivery, and that this was owing to incompatible IT systems. Enablers for the service were that the service reduces practice nurse time and that patients are not required to make an appointment.

The GP surgeries recommended that, in order to recruit more patients, all community pharmacies located around the practice should be involved, and that the community pharmacy route for yearly asthma review should be offered to all asthma patients and not limited to non-attenders.

Pharmacists

Four pharmacists from different community pharmacies attended and an additional pharmacist from another pharmacy was interviewed. Barriers to effective service delivery were identified as the increased time taken to complete reviews and the inability to amend prescriptions themselves. They also identified that non-attenders at GP surgeries are also frequent pharmacy non-attenders (i.e. they use relatives to collect their prescriptions). The elements that enhanced the service were the training that increased self-confidence and the support pack. Improved patient relationships were also seen as encouraging service provision.

The pharmacists recommended that marketing the service should be considered to improve uptake and that the service should be offered to all asthma patients and not just non-attenders. Consideration of how pharmacy technicians could be effectively used within the service model was also recommended.

Patients

One patient who received the service and four patients who were deemed usual ‘non-attenders’ attended the meeting The main reason stated for not attending for asthma review was a perceived lack of need. Barriers to using community pharmacies for yearly asthma reviews were lack of privacy, inadequacy and stigma of consultation rooms, lack of rapport with the community pharmacist, lack of service awareness, and that pharmacists are unable to change prescriptions. The perceived competency of community pharmacists, convenience, increase in choice, and ability to ease pressure on GPs were believed to increase service acceptability and adoption.

To improve service uptake through community pharmacies, the patients recommended better consultation rooms, provision of an online appointment system, screening for patients identified most at need through their inhaler consumption, and having compatible GP community pharmacy computer systems.

Discussion

The driver for this service development was a respiratory nurse specialist, based in secondary care, who had identified a number of preventable asthma-related hospital admissions and wanted to ensure that the NRAD report recommendations were implemented. This was particularly important in a known area of deprivation where outcomes related to asthma are known to be worse. Through the development of a multidisciplinary team, including all relevant stakeholders, it was possible to secure funding to enable the service to be proof-of-concept tested and evaluated. Alignment of the team’s aims with the recently published Murray Review was used to support the argument for funding the project. The project was largely successful owing to the central GP surgery recruiting others to take part and the LPCs aiding identification and recruitment of related community pharmacies.

Community pharmacists demonstrated that they could provide all elements of the service, as agreed at the outset of the project, therefore giving reassurance regarding service standardisation. Furthermore, patients who provided feedback on the service (although small in number) were positive regarding their overall experiences. A total of 27 patients were seen who would not normally have attended a review; two-thirds of these patients were assessed as having either an inappropriate inhaler technique or device. Consequently, the patients in need of a review were largely being identified. Half of the patients seen did not have an asthma management plan; this may be owing to their routine non-attendance for asthma review. The time allocated to the review was insufficient to develop an asthma management plan within the pharmacy and, therefore, all were referred back to their GP surgery. Similarly, so were patients who needed a dose reduction or inhaler change.

Community pharmacists reported that the reviews took between 20 minutes and 40 minutes to deliver. As a result of the perceived improvement in relationships with patients, community pharmacists reported patients returning to seek further advice and, in some cases, to have their inhaler technique rechecked. Consequently, the use of the MUR funding model as it currently stands may not be appropriate. The actual cost of service delivery and any associated follow-up meetings would need to be calculated to ensure that the activity was appropriately remunerated.

The additional cost associated with this workload within the GP surgery would hopefully be justified by improvements in patient quality of life, length of life, reductions in hospitalisation, and unplanned GP visits. However, evidence to test this assertion is not available. The service would be more efficiently delivered if the pharmacist could make the changes to the prescription, respond directly to patients requesting large numbers of reliever inhalers or small numbers of preventer inhalers, and if they were remunerated to develop asthma action plans.

Pharmacists also valued the face-to-face training. This not only improved their confidence, but also provided reassurance to the management team regarding the quality of service delivery. The provision of a support pack that included placebo devices, guidelines and an In-Check Dial was also well received because it enabled the pharmacists to effectively assess inhaler technique and respond to any problems they identified. Evaluation of the training identified the need to focus pharmacists’ time on active learning activities, and the need for the provision of insight by experts and any associated knowledge to be provided in advance.  The training over two evenings, outside normal working hours, was seen as demanding for most pharmacists as they attended after a full day at work. A preference for one day out of work for the training was stated.

The negative patient perceptions associated with a pharmacist consultation room were surprising: these included that the room was used to dispense methadone and discuss personal problems, and as such patients would not want to be seen enter­ing it. Perhaps patient views on this element of pharmacist services should be more robustly sought to identify whether the views identified here are representative and, if so, to identify what needs to change to make them more acceptable. As consultation rooms are more ubiquitously used for provision of services such as influenza vaccinations, the reported stigma associated with their use should diminish.

Perhaps the most positive result was recognition by the GP surgeries that enabling community pharmacists to provide asthma reviews could free up practice nurse time to undertake other activities. They were also supportive of the service being offered through this route for all asthma patients and not just those who do not attend asthma reviews. The pharmacist and patient stakeholder groups independently made the same recommendation. Such a proposal would require close working relationships between the GP surgery and community pharmacies, as well as sharing of records, which aligns with recent recommendations regarding how community pharmacy services should evolve.

There is also a need to consider the most appropriate funding source. If practice nurse time is freed up, then perhaps the GP surgery should fund the service. Similarly, if the service supports a number of GP surgeries, helps to meet local targets and reduces other NHS costs, the clinical commissioning group may be most appropriate to fund it. Alternatively, the national funding scheme for the MUR could be reconfigured as has been recommended for this purpose.

However, the biggest barrier to this service was the creation of non-attender lists; processes within GP surgeries varied significantly from routine list creation within standardised searches to handwritten notes provided by the practice manager. The recent government initiative to put pharmacists in GP surgeries could be used to improve this process.

The regular movement of pharmacists between pharmacies somewhat surprised the pilot study authors, and created unexpected difficulties in ensuring that there was sufficient opportunity for patients from different GP surgeries to attend a community pharmacy for an asthma review. Ultimately, participation of a further GP surgery was lost from the project as a result of this. An additional GP surgery was recruited; however, owing to its late involvement and changes in infrastructure, it failed to deliver any referrals.

Limitations

The small number of patients seen by the community pharmacists reflects the nature of this group of patients who are, by definition, hard to reach. The reasons for the low service uptake were identified as: intentional non-attendance by patients; patients not visiting community pharmacies because third parties collected their medicines; and community pharmacies who were responsible for significant proportions of participating GP surgery patients not participating in this pilot. In a future service, the inclusion of all community pharmacies and pharmacists around participating GP surgeries would help overcome some of these problems.

This was a small-scale service evaluation of a service with limited patient uptake. As a before and after study, without a control arm, it is not possible to predict what would have happened to these patients if this service had not been provided or how much of the change seen is just owing to the regression to the mean (i.e. the phenomenon that when a variable is found to be extreme at the first measurement, it is likely to be closer to the mean on the second measurement).

Similarly, feedback was obtained from a small proportion of patients and other stakeholders. Ideally, data would have been collected on the number of names provided to the pharmacies to determine the recruitment rate; however, this was not considered when this service was set up. Consequently, it is important that the limited quality of these data and evaluation is recognised.

Conclusion

This proof-of-concept service evaluation suggests that the asthma service is both feasible and acceptable, and this is part of the process of developing a definitive trial for evaluation of such a complex intervention. It also provides some insight into the barriers and enablers to its delivery. For the service to work, pharmacists need to be adequately prepared, the remuneration model needs careful consideration, and GP surgery systems for patient identification need to be organised to enable effective communication. Better integration of record systems would help, as would the pharmacists being able to prescribe themselves. The inclusion of pharmacy technicians within the process also needs to be considered.

The next step would be to scale up this service and test it across a geographical area where all GP surgeries, practice-based pharmacists and community pharmacists are actively engaged. Ideally, a more formal evaluation could then be undertaken to enable modelling for service effectiveness and cost-effectiveness.

This innovative approach to improving patient understanding and management of their asthma through access to another healthcare professional who is perceived as competent to deliver the service should be considered by commissioners. This is particularly important if there is a desire to meet the NRAD recommendations that were designed to reduce the large number of preventable asthma deaths occurring each year in the UK[3].

References

https://www.nhlbi.nih.gov/node

https://www.pharmaceutical-journal.com/research/research-article/testing-annual-asthma-reviews-for-those-who-fail-to-attend-proof-of-concept-study/20205089.article#fn_16

https://www.nhlbi.nih.gov/health-topics/pulmonary-function-tests

https://www.pharmaceutical-journal.com/research/research-article/testing-annual-asthma-reviews-for-those-who-fail-to-attend-proof-of-concept-study/20205089.article#fn_4

https://www.pharmaceutical-journal.com/research/research-article/testing-annual-asthma-reviews-for-those-who-fail-to-attend-proof-of-concept-study/20205089.article

https://www.nhlbi.nih.gov/node/4894

https://www.pharmaceutical-journal.com/research/research-article/testing-annual-asthma-reviews-for-those-who-fail-to-attend-proof-of-concept-study/20205089.article#fn_4

https://www.nhlbi.nih.gov/node/3888

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Tiemonium Methylsulfate

Tiemonium Methylsulfate, Indications/Uses, Side Effects, Interactions

Tiemonium Methylsulfate is a synthetic antispasmodic agent. Tiemonium strengthens calcium bonding with phospholipids and proteins thus stabilizing the cell membrane of the GI tract.Tiemonium Methylsulphate is a quarternary ammonium antimuscarinic agent with spasmolytic (antispasmodic) and parasympatholytic (anticholinergic) effects and is used in the relief of visceral spasms.

Indications of Tiemonium Methylsulfate

  • Visceral spasms
  • Tiemonium Methylsulphate may also be used for purposes
  •  It reduces muscle spasms of the intestine, biliary system, bladder and uterus.
  • pain in gastrointestinal and biliary diseases and
  •  urology and gynaecology
  • gastroenteritis,
  • diarrhoea,
  • dysentery,
  • biliary colic,
  • enterocolitis,
  • cholecystitis,
  •  colonopathies,
  • mild cystitis and
  • spasmodic dysmenorrhoea

Contra Indications of Tiemonium Methylsulfate

  • Tiemonium Methylsulphate is a quarternary ammonium antimuscarinic agent with spasmolytic (antispasmodic) and parasympatholytic (anticholinergic) effects and is used in the relief of visceral spasms.
  • angle closure glaucoma
  • urethro prostatic disorder

Dosage of Tiemonium Methylsulfate

Recommended oral dose of Tiemonium Methylsulphate tablet is 2-6 tablets (100-300 mg) daily in divided dosage as required. Xelcom 5 mg/2 ml Injection:

Recommended injectable dose is one or two Tiemonium Methylsulphate Injection three times daily, through Intravenous route slowly or Intramuscular route.

Side Effects of Tiemonium

  • Hypotension
  • Tachycardia
  • Tiemonium Methylsulphate may also cause side-effects

Pregnancy & Lactation

Before using Tiemonium Methylsulfate, inform your doctor about your current list of medications, over the counter products (e.g. vitamins, herbal supplements, etc.), allergies, pre-existing diseases, and current health conditions (e.g. pregnancy, upcoming surgery, etc.). Some health conditions may make you more susceptible to the side-effects of the drug. Take as directed by your doctor or follow the direction printed on the product insert. Dosage is based on your condition. Tell your doctor if your condition persists or worsens. Important counseling points are listed below.

References

  1. [/bg_collapse]

Tiemonium Methylsulfate

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Nitazoxanide is a synthetic benzamide with antiprotozoal activity. Nitazoxanide exerts its antiprotozoal activity by interfering with the pyruvate ferredoxin/flavodoxin oxidoreductase dependent electron transfer reaction, which is essential to anaerobic energy metabolism. PFOR enzyme reduces nitazoxanide, thereby impairing the energy metabolism. However, interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which nitazoxanide exhibits antiprotozoal activity. Nitazoxanide is active against Giardia lamblia and Cryptosporidium parvum.
Nitazoxanide is an antimicrobial with activity against several parasitic worms and protozoa that is used predominantly in the United States in the treatment of giardiasis and cryptosporidiosis. Nitazoxanide therapy has not been reported to cause serum aminotransferase elevations during therapy or clinically apparent liver injury.
Nitazoxanide is a broad-spectrum antiparasitic, antiparasitic and broad-spectrum antiviral drug synthetic nitrothiazolyl-salicylamide derivative and an anti-protozoal agent. It is approved for treatment of infectious diarrhea caused by Cryptosporidium parvum and Giardia lamblia in patients 1 year of age and older. Following oral administration it is rapidly hydrolyzed to its active metabolite, tizoxanide, which is 99% protein bound. Peak concentrations are observed 1–4 hours after administration. It is excreted in the urine, bile, and feces. Untoward effects include abdominal pain, vomiting, and diarrhea.

Mechanism of Action of Nitazoxanide

The antiprotozoal activity of nitazoxanide is believed to be due to interference with the pyruvate, ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism. Nitazoxanide is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that nitazoxanide inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Nitazoxanide is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, nitazoxanide is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.

Indications of Nitazoxanide

  • Dwarf Tapeworm Infection (Hymenolepis nana)
  • Ascariasis
  • Amebiasis
  • Diarrhea with vomiting
  • Giardiasis
  • Ascariasis
  • Cestode infections
  • Clostridium difficile infection recurrence
  • Cryptosporidiosis infection
  • Diarrhea caused by Cryptosporidium parvum
  • Diarrhea caused by Giardia lamblia
  • Giardiasis
  • Trichuriasis
  • For the treatment of diarrhea in adults and children caused by the protozoa Giardia lamblia, and for the treatment of diarrhea in children caused by the protozoan, Cryptosporidium parvum.
  • Nitazoxanide has not been shown to be superior to placebo medication for the management of diarrhea caused by Cryptosporidium parvum in patients with HIV/immunodeficiency

Contra-Indications of Nitazoxanide

  • Nitazoxanide is contraindicated only in individuals who have experienced a hypersensitivity reaction to nitazoxanide or the inactive ingredients of a nitazoxanide formulation

Dosage of Nitazoxanide

 Strengths:  500 mg ,100 mg/5 mL

Amebiasis

  • 500 mg twice daily with food for 3 days.
  • 1000 mg twice daily with food for 14 days or until diarrhea resolves.

Cryptosporidiosis

  • 500 mg twice daily with food for 3 days.
  • 1000 mg twice daily with food for 14 days or until diarrhea resolves.

Giardiasis

  • 500 mg twice daily with food for 3 days.
  • 1000 mg twice daily with food for 14 days or until diarrhea resolves.

Cryptosporidiosis

  • 12 to 47 months: 100 mg (5 mL) by mouth with food every 12 hours for 3 days.
  • 4 to 11 years: 200 mg (10 mL) with food every 12 hours for 3 days.
  • Greater than or equal to 12 years: 500 mg twice daily with food for 3 days.

Pediatric Giardiasis

  • 12 to 47 months: 100 mg (5 mL) by mouth with food every 12 hours for 3 days.
  • 4 to 11 years: 200 mg (10 mL) with food every 12 hours for 3 days.
  • Greater than or equal to 12 years: 500 mg twice daily with food for 3 days.

Ascariasis

  • 2 to 3 years: 100 mg/5 mL
  • 4 to 11 years: 200 mg/10 mL

Hymenolepis nana 

  •  to 3 years: 100 mg/5 mL
  • 4 to 11 years: 200 mg/10 mL

Pediatric Amebiasis

  • 500 mg twice daily with food for 3 days.

Side Effects of Nitazoxanide

The most common side effects 

Common

Rare

Drug Interactions of Nitazoxanide

Nitazoxanide may interact with following drugs, supplements, & may change the efficacy of drugs

Pregnancy & Lactation of Nitazoxanide

 FDA Pregnancy Category B

Pregnancy

There are no data with nitazoxanide in human pregnancy to inform a drug-associated risk. Animal reproductive studies performed in rats and rabbits at doses up to 2 and 30 times the recommended daily human dose demonstrated no evidence of teratogenicity or fetotoxicity due to nitazoxanide.

Breastfeeding

There is no information about the presence of nitazoxanide in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for nitazoxanide and any potential adverse effects on the breastfed infant from nitazoxanide or the mother’s underlying condition.


  1. References

    1. DrugBank

      http://www.drugbank.ca/drugs/DB00507
      http://www.drugbank.ca/drugs/DB00507#targets
      http://www.drugbank.ca/drugs/DB00507#carriers
      http://www.drugbank.ca/drugs/DB00507#enzymes

      https://www.drugs.com/cdi/nitazoxanide-tablets.html

    2. EPA DSStox

      https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID5033757

    3. European Chemicals Agency (ECHA)
      https://echa.europa.eu/substance-information/-/substanceinfo/100.054.465
      https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/49601
    4. Human Metabolome Database (HMDB)

      http://www.hmdb.ca/metabolites/HMDB0014649

      https://www.webmd.com/drugs/2/drug-64747/nitazoxanide-oral/details

    5. ClinicalTrials.gov

      https://clinicaltrials.gov/

    6. DailyMed

      https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=NITAZOXANIDE

    7. FDA Pharm Classes

      https://www.accessdata.fda.gov/spl/data/7df89280-455d-4761-bf82-f8ca7ca2f0f4/7df89280-455d-4761-bf82-f8ca7ca2f0f4.xml

      https://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm

    8. LiverTox

      https://livertox.nlm.nih.gov/Nitazoxanide.htm

    9. NCIt

      https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C47637

    10. FDA/SPL Indexing Data
      https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/
    11. FDA Orange Book

      https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm

    12. MassBank of North America (MoNA)

      http://mona.fiehnlab.ucdavis.edu/spectra/browse?inchikey=YQNQNVDNTFHQSW-UHFFFAOYSA-N

    13. PubMed Health

      http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011421/

    14. Springer Nature Read more …
    15. The Cambridge Structural Database
      http://www.ccdc.cam.ac.uk/pages/Home.aspx
    16. WHO ATC
      https://www.whocc.no/atc/
      https://www.whocc.no/atc_ddd_index/
    17. Wikipedia

      https://en.wikipedia.org/wiki/Nitazoxanide

      https://pubchem.ncbi.nlm.nih.gov

 

Nitazoxanide

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Metronidazole

Metronidazole, Indications, Dosage, Side Effects, Interactions

Metronidazole is a synthetic nitroimidazole derivative with antiprotozoal and antibacterial activities. Although its mechanism of action is not fully elucidated, un-ionized metronidazole is readily taken up by obligate anaerobic organisms and is subsequently reduced by low-redox potential electron-transport proteins to an active, intermediate product. Reduced metronidazole causes DNA strand breaks, thereby inhibiting DNA synthesis and bacterial cell growth.

A metroimidazole is an antibiotic and antiprotozoal medication used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. It has also been proposed as a radiation sensitizer for hypoxic cells.

Machanism of Action of Metronidazole

Metronidazole, a synthetic antibacterial and antiprotozoal agent of the nitroimidazole class, is used against protozoa such as Trichomonas vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against anaerobic bacterial infections and is also used to treat Crohn’s disease, antibiotic-associated diarrhea, and rosacea.Metronidazole is a prodrug. Unionized metronidazole is selective for anaerobic bacteria due to their ability to intracellularly reduce metronidazole to its active form. This reduced metronidazole then covalently binds to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death.

or

Metronidazole is bactericidal, amebicidal, and trichomonacidal in action. The exact mechanism of action of the drug has not been fully elucidated. Metronidazole is un-ionized at physiologic pH and is readily taken up by anaerobic organisms or cells. In susceptible organisms or cells, metronidazoleis reduced by low-redox-potential electron transport proteins (e.g., nitroreductases such as ferredoxin) to unidentified polar product(s) which lack the nitro group. The reduction product(s) appears to be responsible for the cytotoxic and antimicrobial effects of the drug which include disruption of DNA and inhibition of nucleic acid synthesis. Metronidazole is equally effective against dividing and nondividing cells.
or
In in vivo studies in rats given metronidazole in dosages of 2-4 mg/100 g of body weight, the drug reportedly inhibited the development of formalin-induced edema in the rat paw. In vitro in neutrophils, metronidazole has a dose-dependent inhibitory effect on generation of hydrogen peroxide and hydroxyl radicals, oxidants that may cause tissue injury at the site of inflammation. This antioxidant effect appears to be caused by a direct effect on neutrophil function and may contribute to the drug’s anti-inflammatory effect in vivo.

Indications of Metronidazole

  • Bacterial Vaginitis
  • Bacterial Infection
  • Amebiasis
  • Aspiration Pneumonia
  • Dental Abscess
  • Clostridium difficile-associated diarrhea and colitis,
  • Helicobacter pylori infection and duodenal ulcer disease, bacterial vaginosis,
  • Giardia lamblia gastro-enteritis, amebiasis
  • STD Prophylaxis
  • Bacteremia
  • Balantidium coli
  • Bone infection
  • Clostridial Infection
  • Crohn’s Disease, 
  • Deep Neck Infection
  • Dientamoeba fragilis
  • Diverticulitis
  • Dracunculiasis
  • Endocarditis
  • Giardiasis
  • Helicobacter Pylori Infection
  • Intraabdominal Infection
  • Joint Infection
  • Lemierre’s Syndrome
  • Meningitis
  • Nongonococcal Urethritis
  • Pelvic Inflammatory Disease
  • Peritonitis
  • Pneumonia
  • Pouchitis
  • Pseudomembranous Colitis
  • Skin or Soft Tissue Infection
  • Surgical Prophylaxis
  • Trichomoniasis
  • For the treatment of anaerobic infections and mixed infections, surgical prophylaxis requiring anaerobic coverage, Clostridium difficile-associated diarrhea and colitis, Helicobacter pylori infection and duodenal ulcer disease, bacterial vaginosis, Giardia lamblia gastro-enteritis, amebiasis caused by Entamoeba histolytica, acne rosacea (topical treatment), and Trichomonas infections.

Therapeutic Indications of Metronidazole

  • Oral metronidazole (extended release formulation) is used in the treatment of bacterial vaginosis caused by Gardnerella vaginalis, Mobiluncus spp, mycoplasma hominis and anaerobes (peptostreptococcus spp and Bacteroides spp).
  • Metronidazole is used in the treatment of periodontal infections caused by Bacteroides species.
  • Oral metronidazole is used in the treatment of giardiasis caused by Giardia lamblia.
  • Some studies indicate that metronidazole may be effective, in combination with bismuth subsalicylate or colloidal bismuth subcitrate, and other oral antibiotic therapy, such as ampicillin or amoxicillin, in the treatment of Helicobacter pylori-associated gastritis and duodenal ulcer. However, metronidazole resistance may occur, especially in patients who have been previously exposed to metronidazole.
  • Metronidazole is used in the treatment of dracunculiasis (guinea worm infection) caused by Dracunculus medinensis. It decreases the inflammation around the ulcer, increasing the ease of removing the worm.
  • Metronidazole is used in the treatment of antibiotic-associated diarrhea and colitis caused by Clostridium difficile.
  • Metronidazole is used in the treatment of inflammatory bowel disease.
  • Metronidazole is used in the treatment of Balantidium coli infection.
  • Oral metronidazole is indicated in the treatment of symptomatic and asymptomatic trichomoniasis, in males and females, caused by Trichomonas vaginalis.
  • Metronidazole is indicated in the treatment of skin and soft tissue infections caused by Bacteroides species, including the Bacteroides fragilis group. Clostridium species, Fusobacterium species, Peptococcus species, and Peptostreptococcus species.
  • Metronidazole is indicated in the treatment of bacterial septicemia caused by Bacteroides species, including the Bacteroides fragilis group, and Clostridium species.
  • Metronidazole is indicated in the treatment of lower respiratory tract infections, including pneumonia, emphysema, and lung abscess, caused by Bacteroides species, including the Bacteroides fragilis group.
  • Intravenous metronidazole is indicated for the prophylaxis of perioperative infections during colorectal surgery.
  • Metronidazole is indicated in the treatment of female pelvic infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infections, caused by Bacteroides species, including the Bacteroides fragilis group, Clostridium species, Peptoccus species, and Peptostreptococcus species.
  • Metronidazole is indicated in the treatment of intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species, including the Bacteroides fragilis group, Clostridium species, Eubacterium species, Peptococcus species, and Peptostreptococcus species
  • Metronidazole is indicated in the treatment of endocarditis caused by Bacteroides species, including the Bacteroides fragilis group.
  • Metronidazole is indicated in the treatment of CNS infections, including meningitis, caused by Bacteroides species, including the Bacteroides fragilis group.
  • Metronidazole is indicated in the treatment of brain abscess caused by Bacteroides species, including the Bacteroides fragilis group.
  • Metronidazole is indicated in the treatment of bone and joint infections caused by Bacteroides species, including the Bacteroides fragilis group (Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus).
  • Oral metronidazole is indicated in the treatment of acute intestinal amebiasis caused by Entamoeba histolytica. Metronidazole may not eradicate intestinal amebic infections, requiring treatment with a luminal amebicide.
  • Metronidazole is indicated in the treatment of extraintestinal amebiases, including amebic liver abscess, caused by Entamoeba histolytica. When used in the treatment of invasive amebiasis, metronidazole should be administered concurrently or sequentially with a luminal amebicide (eg, iodoquinol, paromomycin, tetracycline, diloxanide furoate). When used in the treatment of amebic liver abscesses, metronidazole therapy does not obviate the need for aspiration of the abscess.
  • Metronidazole is not effective against facultative anaerobes, obligate aerobes, Propionibacterium acnes, Actinomyces species, or Candida albicans.

Contra Indications of Metronidazole

Dosage of Metronidazole

Strengths:  250 mg;400 mg 375 mg; 500 mg; 750 mg; 500 mg/100 mL;

Bacterial Infection

IV

  • Loading dose: 15 mg/kg IV once infused over 1 hour
  • Maintenance dose: 7.5 mg/kg IV infused over 1 hour every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Oral ,Immediate-release Capsules and Tablets

  • 7.5 mg/kg orally every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Amebiasis

Acute Intestinal Amebiasis (Acute Amebic Dysentery)

  • Immediate-release capsules and tablets: 750 mg orally 3 times a day for 5 to 10 days

Amebic Liver Abscess

  • Immediate-release capsules and tablets: 500 to 750 mg orally 3 times a day for 5 to 10 days

Trichomoniasis

  • Immediate-release Capsules: 375 mg orally twice a day for 7 consecutive days

Immediate-release Tablets

  • One-day regimen: 2 g orally as a single dose or 1 g twice given in the same da
  • Seven-day regimen: 250 mg orally 3 times a day for 7 consecutive days

US CDC recommendations ,Immediate-release Tablets

  • Recommended regimen: 2 g orally as a single dose
  • Alternative regimen: 500 mg orally twice a day for 7 days

Trichomoniasis in HIV-infected women

  • Immediate-release tablets: 500 mg orally twice a day for 7 days

Treatment failure with single-dose therapy and reinfection is excluded

  • Immediate-release tablets: 500 mg orally twice a day for 7 days; for patients failing this regimen, 2 g orally once a day for 7 days should be considered

Helicobacter pylori Infection

Some experts recommend

  • Bismuth quadruple therapy: 250 mg orally 4 times a day
  • Clarithromycin-based triple therapy: 500 mg orally twice a day
  • Duration of therapy: 10 to 14 days

Pelvic Inflammatory Disease

US CDC recommendations
Mild to moderately severe acute pelvic inflammatory disease (PID)

  • Immediate-release tablets: 500 mg orally twice a day for 14 days

Bacterial Vaginosis

  • Extended-release Tablets: 750 mg orally once a day for 7 consecutive days

US CDC recommendations

  • Immediate-release tablets: 500 mg orally twice a day for 7 days

Intraabdominal Infection

IV

  • Loading dose: 15 mg/kg IV once infused over 1 hour
  • Maintenance dose: 7.5 mg/kg IV infused over 1 hour every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Oral

  • Immediate-release capsules and tablets: 7.5 mg/kg orally every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

IDSA and SIS recommendations

  • Immediate-release tablets: 500 mg IV every 8 to 12 hours or 1500 mg IV every 24 hours

Peritonitis

IV

  • Loading dose: 15 mg/kg IV once infused over 1 hour
  • Maintenance dose: 7.5 mg/kg IV infused over 1 hour every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Oral

  • Immediate-release capsules and tablets: 7.5 mg/kg orally every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Liver Abscess

IV

  • Loading dose: 15 mg/kg IV once infused over 1 hour
  • Maintenance dose: 7.5 mg/kg IV infused over 1 hour every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Oral

  • Immediate-release capsules and tablets: 7.5 mg/kg orally every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Joint Infection

IV:
-Loading dose: 15 mg/kg IV once infused over 1 hour
-Maintenance dose: 7.5 mg/kg IV infused over 1 hour every 6 hours
-Maximum dose: 4 g per day
-Duration of therapy: 7 to 10 days

Oral

  • Immediate-release capsules and tablets: 7.5 mg/kg orally every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Osteomyelitis

IV

  • Loading dose: 15 mg/kg IV once infused over 1 hour
  • Maintenance dose: 7.5 mg/kg IV infused over 1 hour every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Oral

  • Immediate-release capsules and tablets: 7.5 mg/kg orally every 6 hours
  • Maximum dose: 4 g per day
  • Duration of therapy: 7 to 10 days

Pediatric Bacterial Infection

American Academy of Pediatrics (AAP) recommendations ,Neonates
7 days or less

  • Up to 2 kg: 7.5 mg/kg IV every 12 hours
  • Greater than 2 kg: 7.5 mg/kg IV every 8 hours

8 to 28 days

  • Up to 2 kg: 7.5 mg/kg IV every 12 hours
  • Greater than 2 kg: 7.5 mg/kg IV every 6 hours
  • Postmenstrual age less than 34 weeks: 7.5 mg/kg IV every 12 hours
  • Postmenstrual age 34 to 40 weeks: 7.5 mg/kg IV every 8 hours
  • Postmenstrual age greater than 40 weeks: 7.5 mg/kg IV every 6 hour

1 month or older

  • IV: 22.5 to 40 mg/kg/day IV in 3 divided doses
  • Maximum dose: 1.5 g/day

Oral

  • 30 to 50 mg/kg/day orally in 3 divided doses
  • Maximum dose: 2.25 g/day

Side Effects of Metronidazole

The most common side effects 

Common

Rare

Drug Interactions of Metronidazole

Metronidazole may interact with following drugs, supplements, & may change the efficacy of drugs

Pregnancy & Lactation of Metronidazole

FDA Pregnancy Category B 
Pregnancy

According to the manufacturer, oral metronidazole is contraindicated during the first trimester of pregnancy in patients with trichomoniasis. However, the CDC states that metronidazole can be used for trichomoniasis at any stage of pregnancy as studies have not demonstrated an association between metronidazole and teratogenic effects.

Lactation

Metronidazole is excreted into breast milk. Breastfeeding is not recommended during treatment with systemic products. While there is some systemic absorption from topical and vaginal products, plasma concentrations would be lower than demonstrated with systemic formulations; however, caution is still advised. Metronidazole is a mutagen in vitro and has been shown to be carcinogenic in animal studies. In general, increased oral and rectal Candida colonization and loose stools have been reported in infants exposed to metronidazole via breast milk.


  1. References

    1. DrugBank

      http://www.drugbank.ca/drugs/DB00916
      http://www.drugbank.ca/drugs/DB00916#enzymes
      http://www.drugbank.ca/drugs/DB00916#targets

      https://www.drugs.com/metronidazole.html

    2. HSDB

      https://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+443-48-1

    3. Human Metabolome Database (HMDB)

      http://www.hmdb.ca/metabolites/HMDB0015052

    4. ChemIDplus
      https://chem.nlm.nih.gov/chemidplus/sid/0000443481
      https://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp
    5. DTP/NCI

      https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=757118

      https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=69587

      https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=50364

    6. EPA DSStox

      https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID2020892

    7. European Chemicals Agency (ECHA)

      https://echa.europa.eu/substance-information/-/substanceinfo/100.006.489

      https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/122521

    8. FDA Pharm Classes

      https://www.accessdata.fda.gov/spl/data/9ef71064-51c2-477c-b844-6cd39b67edc2/9ef71064-51c2-477c-b844-6cd39b67edc2.xml
      htps://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm

    9. LiverTox

      https://livertox.nlm.nih.gov/Metronidazole.htm

    10. NCIT

      https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C651

    11. ClinicalTrials.gov

      https://clinicaltrials.gov/

    12. DailyMed

      https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=PYLERA

      https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=METRONIDAZOLE

    13. FDA/SPL Indexing Data
      https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/
    14. https://www.webmd.com/drugs/2/drug-6426/metronidazole-oral/details/list-contraindications
    15. EU Community Register of Medicinal Products

      https://ec.europa.eu/health/documents/community-register/html/o875.htm

    16. EPA Office of Pesticide Programs
      . Read more.

      http://www.ipmcenters.org/Ecotox/index.cfm

    17. FAO/WHO Food Additive Evaluations (JECFA)

      http://apps.who.int/food-additives-contaminants-jecfa-database/chemical.aspx?chemID=1482

    18. FDA Orange Book
      https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm
    19. SpectraBase
      https://spectrabase.com/compound/JFkJwk2sULC#HdF0T41T3NE
      https://spectrabase.com/compound/JFkJwk2sULC#8GCabMZST1m
      https://spectrabase.com/compound/JFkJwk2sULC#EHGeI5roo5K
      https://spectrabase.com/compound/JFkJwk2sULC#HnBVDInEb9a
      https://spectrabase.com/compound/JFkJwk2sULC#10mqscbTcU2
      https://spectrabase.com/compound/JFkJwk2sULC#CPP8EpjmR63
      https://spectrabase.com/compound/JFkJwk2sULC#FYFVNyw5ei0
      https://spectrabase.com/compound/JFkJwk2sULC#5nJn4e6QFpk
      https://spectrabase.com/compound/JFkJwk2sULC#4JYqtYHPj1u
      https://spectrabase.com/compound/JFkJwk2sULC#2EhAYCZSIIE
      https://spectrabase.com/compound/JFkJwk2sULC#BzHCiCimee6
    20. MassBank of North America (MoNA)

      http://mona.fiehnlab.ucdavis.edu/spectra/browse?inchikey=VAOCPAMSLUNLGC-UHFFFAOYSA-N

    21. NIST

      http://www.nist.gov/srd/nist1a.cfm

    22. PubMed Health

      http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0001181/

      http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011199/

      http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011192/

      http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011193/

      http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011195/

    23. Springer Nature more …
    24. The Cambridge Structural Database

      http://www.ccdc.cam.ac.uk/pages/Home.aspx

    25. WHO ATC

      https://www.whocc.no/atc/

      https://www.whocc.no/atc_ddd_index/

    26. Wikipedia

      https://en.wikipedia.org/wiki/Metronidazole

      https://pubchem.ncbi.nlm.nih.gov

 

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Medication/Drugs

Medication/Drugs; Disease Conditions, Treatment,

Medication/Drugs is any substance (other than food that provides nutritional support) that, when inhaled, injected, smoked, consumed, absorbed via a patch on the skin, or dissolved under the tongue causes a temporary physiological (and often psychological) change in the body.

In pharmacology, a drug is a chemical substance of known structure, other than a nutrient of an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. A pharmaceutical drug, also called a medication or medicine, is a chemical substance used to treat, cure, prevent, or diagnose a disease or to promote well-being. Traditionally drugs were obtained through extraction from medicinal plants, but more recently also by organic synthesis.Pharmaceutical drugs may be used for a limited duration, or on a regular basis for chronic disorders.

This list contains the names of many medical problems and the names of drugs that may be used for their treatment. The drugs are listed either as a generic name or drug class name. Specific brands are not shown. You may use this tool to find brand name versions of generics. This list is intended only as a guide and is not meant to be 100% complete. Use it for general reference.
The inclusion of a drug does not mean it is necessarily an appropriate treatment for you. Also, the doctor may prescribe the treatment that is not listed, but according to your medical history is quite appropriate for your medical condition.
Condition Commonly Used Drugs
Acid Indigestion and Upset Stomach Antacids
Bismuth Subsalicylate
Histamine H2 Receptor Antagonists
Hyoscyamine
Proton Pump Inhibitors
Simethicone
Sodium Bicarbonate
Acne Anti-acne Cleansing (Topical)
Topical Antibiotics (Clindamycin, Erythromycin)
Oral Antibiotics(Tetracyclines, Metronidazole)
Azelaic Acid
Benzoyl Peroxide
Isotretinoin
Keratolytics
Retinoids (Topical)
Actinic Keratoses Fluorouracil
Masoprocol
Acute Myocardial Infarction Antithrombotic Agents
Nitroglycerin
Angiotensin Converting Enzyme (ACE) Inhibitors
Beta-Adrenergic Blockers
Angiotensin-Receptor Blockers
Thrombolytics
Addison’s Disease Adrenocorticoids (Systemic)
Aging Dehydroepiandrosterone (DHEA)
AIDS and HIV Infection Fusion Inhibitors
Non-Nucleoside Reverse Transcriptase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors
Nucleotide Reverse Transcriptase Inhibitors
Protease Inhibitors
Alcohol Withdrawal Benzodiazepines
Beta-Adrenergic Blocking Agents
Carbamazepine
Disulfiram
Hydroxyzine
Lithium
Naltrexone
Thiamine
Phenobarbital
Allergies and Allergic Reactions Adrenocorticoids (Nasal Inhalation, Oral Inhalation, Systemic)
Antihistamines
Antihistamines, Non-sedating
Antihistamines, Phenothiazine-Derivative
Azelastine
Cromolyn
Decongestants (Ophthalmic)
Ephedrine
Hydroxyzine
Alopecia Dutasteride
Finasteride
Minoxidil
Altitube Illness Carbonic Anhydrase Inhibitors
Alzheimer’s Disease Cholinesterase Inhibitors
Memantine
Amebiasis Chloroquine
Iodoquinol
Metronidazole
Amenorrhea Bromocriptine
Progestins
Amyotrophic Lateral Sclerosis (ALS) Riluzole
Anemia Adrenocorticoids (Systemic)
Androgens
Cyclosporine
Folic Acid
Iron Supplements
Leucovorin
Vitamin B-12
Angina Antiplatelet Agents
Beta Adrenergic Blocking Agents
Calcium Channel Blockers
Ranolazine
Nitrates
Anorexia Calcium Carbonate
Calcium Gluconate
Potassium Chloride
Antidepressants, Tricyclic
Progestins
Fluoxetine
Anxiety Antidepressants (Tricyclic, SSRIs, SNRIs)
Barbiturates
Benzodiazepines
Beta Adrenergic Blocking Agents
Buspirone
Ergotamine, Beladonna and Phenobarbital
Haloperidol
Hydroxyzine
Loxapine
Meprobamate
Phenothiazines
Thiothixene
Appetite Stimulant Antihistamines
Dronabinol
Megestrol
Arthritis (Osteoarthritis, Rheumatoid Arthritis) Acetaminophen
Adrenocorticoids (Oral Inhalation, Systemic)
Anakinra
Antihistamines, Non-sedating
COX-2 Inhibitors
NSAIDs
Aspirin
Azathioprine
Bronchodilators, Adrenergic
Bronchodilators, Xanthine
Capsaicin
Chloroquine
Cyclosporine
Gold Compounds
Hydroxychloroquine
Leukotriene Modifiers
Methotrexate
Tumor Necrosis Factor Blockers
Asthma Adrenocorticoids (Nasal Inhalation, Oral Inhalation, Systemic)
Bronchodilators, Adrenergic
Bronchodilators, Xanthine
Cromolyn
Ephedrine
Ipratropium
Leukotriene Modifiers
Nedocromil
Theophylline
Athlete’s Foot Antibacterials
Antifungals (Topical)
Attention Deficit Hyperactivity Disorder (ADHD) Amphetamines
Atomoxetine
Dexmethylphenidate
Methylphenidate
Pemoline
Guanfacine
Clonidine
Autism Haloperidol
Bacterial Infections Acetohydroxamic Acid (AHA)
Antibiotics
Benign Prostate Hyperplasia (BPH) Alpha Adrenergic Receptor Blockers
Dutasteride
Finasteride
Bipolar Disorder Antipsychotics (Quetiapine, Olanzapine, Risperidone, Ziprasidone, Haloperidol)
Anticonvulsants (Carbamazepine, Divalproex, Valproate Acid)
Lithium
Bites and Stings Adrenocorticoids (Topical)
Anesthetics (Topical)
Bladder Inflammation Dimethyl Sulfoxide
Bladder Spasms Clidinium
Propantheline
Oxybutynin
Bleeding Antifibrinolytic Agents
Vitamin K
Blood Circulation Cyclandelate
Intermittent Claudication Agents
Isoxsuprine
Vitamin E
Blood Clots Anticoagulants (Oral)
Antiplatelets (Clopidogrel, Dipyridamole, Ticlopidine)
Aspirin
Bronchial Spasms Anticholinergics
Bronchodilators, Adrenergic
Bronchitis Bronchodilators, Xanthine
Dextromethorphan
Ipratropium
Cephalosporins
Fluoroquinolones
Macrolides
Sulfonamides
Tetracyclines
Bulimia Antidepressants, Tricyclic
Lithium
Selective Serotonin Reuptake Inhibitors (SSRIs)
Burns Anesthetics (Topical)
Zinc Supplements
Silver Sulfadiazine
Neomycin/Polymyxin B/Bacitracin topical
Bursitis Adrenocorticoids (Systemic)
NSAIDs
Aspirin
Cancer Adrenocorticoids (Systemic)
Aminoglutethimide
Androgens
Antiandrogens, Nonsteroidal
Antifungals, Azoles
Busulfan
Capecitabine
Cholarmbucil
Cyclophosphamide
Estramustine
Estrogens
Etoposide
Flutamide
Hydroxyurea
Imatinib
Levamisole
Lomustine
Melphalan
Mercaptopurine
Methotrexate
Mitotane
Paclitaxel
Procarbazine
Progestins
Tamoxifen
Testolactone
Thioguanine
Thyroid Hormones
Toremifene
Cancer Of The Skin Fluorouracil
Masoprocol
Mechlorethamine (Topical)
Canker Sores (Aphthous Ulcers) Amlexanox
Bioadherent
Anesthetics (Mucosal-Local)
Corticosteroids
Chickenpox Acyclovir
Acetaminophen
Antihistamines
Cholesterol, High Cholestyramine
Colestipol
Ezetimibe
Gemfibrozil
HMG-CoA Reductase Inhibitors
Neomycin (Oral)
Niacin
Raloxifene
Chronic Obstructive Pulmonary Disease (COPD) Adrenocorticoids (Systemic)
Bronchodilators, Adrenergic
Bronchodilators, Xanthine
Ipratropium
Tiotropium
Cirrhosis Colchicine
Cyclosporine
Thiamine (Vitamin B-1)
Colds and Cough Acetaminophen
Anticholinergics
Antihistamines
Antihistamines, Non-sedating
NSAIDs
Aspirin
Dextromethorphan
Ephedrine
Guaifenesin
Phenylephrine
Phenylephrine (Ophthalmic)
Pseudoephedrine
Colic Hyoscyamine
Simethicone
Congestion Bronchodilators, Adrenergic
Ephedrine
Oxymetazoline
Phenylephrine
Pseudoephedrine
Xylometazoline
Congestive Heart Failure Angiotensin-Converting Enzyme (ACE) Inhibitors
Digitalis Preparations
Beta-Adrenergic Blocking Agents
Beta-Adrenergic Blocking Agents and Thiazide
Diuretics, Loop
Diuretics, Potassium-Sparing
Diuretics, Potassium-Sparing and Hydrochlorothiazide
Diuretics, Thiazide
Nitrates
Conjunctivitis (Pink Eye) Antibacterials (Ophthalmic)
Antivirals (Ophthalmic)
Conjunctivitis, Seasonal Allergic NSAIDs (Ophthalmic)
Antiallergic Agents (Ophthalmic)
Constipation Laxatives, Bulk-Forming (Psyllium)
Laxatives, Osmotic (Lactulose)
Laxatives, Softener/Lubricant
Laxatives, Stimulant (Senna, Bisacodyl, Cascara Sagrada)
Lubiprostone, Linaclotide
Tegaserod
Contraception (Birth Control) Contraceptives, Oral and Skin
Contraceptives, Vaginal
Contraceptives, Vaginal (Spermicides)
Convulsions (Epilepsy, Seizures) Anticonvulsants, Hydantoin
Anticonvulsants, Succinimide
Barbiturates
Benzodiazepines
Carbamazepine
Divalproex
Felbamate
Gabapentin
Lamotrigine
Levetiracetam
Oxcarbazepine
Primidone
Topiramate
Valproic Acid
Zonisamide
Corneal Ulcers Antibacterials (Ophthalmic)
Cushing’s Disease Adrenocorticoids (Systemic)
Aminoglutethimide
Antifungals, Azoles
Metyrapone
Mitotane
Trilostane
Cystitis Phenazopyridine
Sulfonamides and Phenazopyridine
Nitrofurantoin
Fosfomycin
Fluoroquinolones
Cephalosporins
Penicillins
Dandruff Antifungals (Topical)
Antiseborrheics
Coal Tar
Dementia Buspirone
Cholinesterase Inhibitors
Ergoloid Mesylates
Memantine
Haloperidol
Depression Antidepressants
Ergoloid Mesylates
Loxapine
Maprotiline
Methylphenidate
Selegiline
Dermatitis Adrenocorticoids (Systemic)
Adrenocorticoids (Topical)
Anesthetics (Topical)
Antiseborrheics
Coal Tar
Colchicine
Dapsone
Keratolytics
Dermatomyositis Aminobenzoate Potassium
Diabetes Antidiabetic Agents
Diarrhea Attapulgite
Bismuth Subsalicylate
Charcoal Activated
Difenoxin and Atropine
Diphenoxylate and Atropine
Kaolin and Pectin
Kaolin, Pectin, Belladonna and Opium
Loperamide
Nitazoxanide
Paregoric
Dietary Supplements Calcium Supplements
Iron Supplements
Niacin
Vitamin A
Vitamin B-12
Vitamin C
Vitamin D
Vitamin E
Vitamin K
Digestive Spasms Clidinium
Difenoxin and Atropine
Dicyclomine
Hyoscyamine
Propantheline
Diverticulitis
Drowsiness Caffeine
Orphenadrine, Aspirin and Caffeine
Dry Eyes Protectant (Ophthalmic)
Ear Allergies Anti-Inflammatory Drugs, Steroidal (Otic)
Ear Infections (Otitis Media) Antibiotics for Otitis Media
Antibacterials (Otic)
Anti-Inflammatory Drugs, Steroidal (Otic)
Antipyrine
Phenylephrine
Ear Wax Antipyrine and Benzocaine (Otic)
Eczema Adrenocorticoids (Topical)
Antibacterials, Antifungals (Topical)
Coal Tar
Doxepin (Topical)
Keratolytics
Emphysema Adrenocorticoids (Systemic)
Bronchodilators, Adrenergic
Bronchodilators, Xanthine
Ipratropium
Tiotropium
Endometriosis Danazol
Nafarelin
Goserelin
Leuprolide
Oral Contraceptives
Erectile Dysfunction (Impotence) Alprostadil
Erectile Dysfunction Agents
Papaverine
Yohimbe
Esophagitis Histamine H2 Receptor Antagonists
Metoclopramide
Proton Pump Inhibitors
Estrogen Deficiency Estrogen
Eye Allergies Antiallergic Agents (Ophthalmic)
Eye Conditions Antibacterials (Ophthalmic)
Cromolyn
Cycloplegic, Mydriatic (Ophthalmic)
Cyclopentolate (Ophthalmic)
Decongestants (Ophthalmic)
Natamycin (Ophthalmic)
Phenylephrine (Ophthalmic)
Fatigue Caffeine
Fever Acetaminophen
NSAIDs
Aspirin
Barbiturates, Aspirin and Codeine
Chlorzoxazone and Acetaminophen
Narcotic Analgesics and Aspirin
Salicylates
Fibrocystic Breast Disease Danazol
Vitamin E
Fluid Retention (Edema, Swelling) Angiotensin Converting Enzyme (ACE) Inhibitors and Hydrochlorothiazide
Carbonic Anhydrase Inhibitors
Clonidine and Chlorthalidone
Diuretics, Loop
Diuretics, Potassium-Sparing
Diuretics, Thiazide
Guanethidine and Hydrochlorothiazide
Hydralazine and Hydrochlorothiazide
Indapamide
Methyldopa and Thiazide Diuretics
Reserpine, Hydralazine and Hydrochlorothiazide
Fungal Infections (Ringworm) Antifungals, Azoles
Antifungals, Topical
Griseofulvin
Nystatin
Gallstones Ursodiol
Gastroesophageal Reflux Histamine H2 Receptor Antagonists
Proton Pump Inhibitors
Sucralfate
Genital Warts (Condyloma Acuminatum) Podofilox
Imiquimod
Papillomavirus Vaccines
Giardiasis Furazolidone, Quinacrine, Metronidazole, Nitazoxanide, Tinidazole
Gingivitis and Gum Disease Chlorhexidine
Erythromycins
Penicillins
Tetracyclines
Glaucoma Antiglaucoma, Adrenergic Antagonists
Antiglaucoma, Anticholinesterases
Antiglaucoma, Beta Blockers
Antiglaucoma, Carbonic Anhydrase Inhibitors
Antiglaucoma, Cholinergic Agonists
Antiglaucoma, Prostaglandins
Carbonic Anhydrase Inhibitors
Gonorrhea Cephalosporins
Erythromycins
Fluoroquinolones
Macrolide Antibiotics
Penicillins
Tetracyclines
Gout Adrenocorticoids (Systemic)
Allopurinol
NSAIDs
Colchicine
Meloxicam
Probenecid
Probenecid and Colchicine
Sulfinpyrazone
Hair Loss (Baldness) Antharil (Topical)
Finasteride
Minoxidil (Topical)
Hay Fever Antiallergic Agents (Ophthalmic)
Antihistamines
Antihistamines, Non-sedating
Antihistamine, Phenothiazine-Derivative
Ephedrine
Guaifenesin
Hydroxyzine
Meclizine
Orphenadrine
Phenylephrine (Ophthalmic)
Headache (Cluster, Migraine, Sinus, Tension, Vascular) Acetaminophen, Fioricet
Antidepressants, Tricyclic
Antihistamines
NSAIDs
Aspirin
Barbiturates, Aspirin and Codeine
Beta Adrenergic Blocking Agents
Buspirone
Butorphanol
Caffeine
Calcium Channel Blockers
Clonidine
Divalproex
Ergotamine
Ergotamine, Belladonna and Phenobarbital
Isometheptene, Dichloralphenazone and Acetaminophen
Lithium
Methysergide
Monoamine Oxidase Inhibitors
Triptans
Heart Rhythm Disorders (Irregular Heartbeat) Amiodarone
Beta-Adrenergic Blocking Agents
Calcium Channel Blockers
Digitalis Preparations
Disopyramide
Dofetilide
Flecainide Acetate
Mexiletine
Moricizine
Procainamide
Propafenone
Quinidine
Tocainide
Heartburn (Indigestion) Antacids
Histamine H2 Receptor Antagonists
Proton Pump Inhibitors
Sodium Bicarbonate
Hemorrhoids Adrenocorticoids (Topical)
Anesthetics (Rectal)
Herpes Antivirals (Topical)
Antivirals for Herpes Virus
Hives (Urticaria) Antihistamines
Antihistamines, Non-sedating
Antihistamines, Phenothiazine-Derivative
Hydroxyzine
Huntington’s Haloperidol
Hypercalcemia Colesevelam
Colestipol
Dextrothyroxine
HMG-CoA Reductase Inhibitors
Hyperglycemia Acarbose
Metformin
Hypertension (High Blood Pressure)
Hyperthyroidism Antithyroid Drugs
Hypertriglyceridemia Fibrates
Gemfibrozil
Hypoglycemia Glucagon
Miglitol
Hypothyroidism Dextrothyroxine
Thyroid Hormones
Incontinence Tolterodine
Infertility Bromocriptine
Clomiphene
Danazol
Progestins
Inflammation Acetaminophen and Salicylates
NSAIDs
COX-2 Inhibitors
Aspirin
Mesalamine
Narcotic Analgesics and Aspirin
Salicylates
Inflammatory Bowel Disease (Colitis, Crohn’s Disease) Adrenocorticoids (Systemic)
Cyclosporine
Mesalamine
Metronidazole
Olsalazine
Influenza (Flu) Antivirals for Influenza
Antivirals for Influenza, Neuraminidase Inhibitors
Ribavirin
Insomnia Belladonna Alkaloids and Barbiturates
Chloral Hydrate
Melatonin
Meprobamate
Intermittent Claudication Intermittent Claudication Agents
Irritable Bowel Syndrome Tegaserod
Itching Adrenocorticoids (Topical)
Doxepin (Topical)
Jet Lag Melatonin
Jock Itch Antifungals (Topical)
Joint Pain NSAIDs
COX-2 Inhibitors
Aspirin
Probenecid and Colchicine
Kidney Stones Allopurinol
Cellulose Sodium Phosphate
Citrates
Diuretics, Thiazide
Penicillamine
Sodium Bicarbonate
Tiopronin
Labyrinthitis Antihistamines, Phenothiazine-Derivatives
Benzodiazepines
Meclizine
Leg Pain or Cramps Cyclandelate
Intermittent Claudication Agents
Orphenadrine
Pentoxifylline
Quinine
Leukemia Imatinib
Thioguanine
Lice Pediculicides
Lupus (Skin and Systemic) NSAIDs
COX-2 Inhibitors
Adrenocorticoids (Systemic)
Adrenocorticoids (Topical)
Hydroxychloroquine
Methotrexate
Quinacrine
Lyme Disease Cephalosporins
Erythromycins
Macrolide Antibiotics
Penicillins
Tetracyclines
Malabsorption Vitamin K
Quinacrine
Malaria Antimalarial
Atovaquone
Chloroquine
Hydroxychloroquine
Primaquine
Proguanil
Quinidine
Quinine
Sulfadoxine and Pyrimethamine
Male Hormone Deficiency Androgens
Melanoma Hydroxyurea
Levamisole
Melphalan
Meniere’s Disease Antihistamines
Benzodiazepines
Meclizine
Scopolamine (Hyoscine)
Menopause Estrogens
Progestins
Menstrual Cramps (Dysmenorrhea) NSAIDs
COX-2 Inhibitors
Contraceptives (Oral)
Menstruation, Excessive (Menorrhagia) Contraceptives, Oral
Danazol
Estrogens
Progestins
Mental and Emotional Disturbances Loxapine
Molindone
Rauwolfia Alkaloids
Risperidone
Motion Sickness Antihistamines
Antihistamines, Non-sedating
Antihistamines, Phenothiazine-Derivative
Clotrimazole
Cyclizine
Diphenidol
Meclizine
Scopolamine
Multiple Sclerosis Adrenocorticoids (Systemic)
Baclofen
Tizanidine
Muscle Cramp, Spasm, Strain Baclofen
Chlorzoxazone and Acetaminophen
Dantrolene
Muscle Relaxants, Skeletal (Cyclobenzaprine, Carisoprodol, Orphenadrine, Tizanidine)
Aspirin and Caffeine
Quinine
Myasthenia Gravis Adrenocorticoids (Systemic)
Antimyasthenics
Azathioprine
Cyclosporine
Narcolepsy Amphetamines
Methylphenidate
Modafinil
Narcotic Withdrawal Buprenorphine and Naloxone
Nasal Allergy Adrenocorticoids (Nasal Inhalation)
Nausea and Vomiting Antihistamines Phenothiazine-Derivative
Bismuth Subsalicylate
Diphenidol
Dronabinol
Hydroxyzine
Metoclopramide
Nabilone
Phenothiazines
Scopolamine
Trimethobenzamide
Neural Tube Defects (prevention) Folic Acid
Night Blindness Beta Carotene
Obesity Appetite Suppressants
Lorcaserin
Phentermine
Orlistat
Liraglutide
Bupropion and Naltrexone
Obsessive Compulsive Disorder Antidepressants, Tricyclic
Selective Serotonin Reuptake Inhibitors (SSRIs)
Ocular Hypertension Beta Adrenergic Blocking Agents (Ophthalmic)
Dorzolamide
Osteoporosis Alendronate
Bone Formation Agents
Calcitonin
Calcium Supplements
Estrogens
Raloxifene
Sodium Fluoride
Vitamin D
Overactive Bladder Tolterodine, Oxybutynin, Trospium, Darifenacin, Solifenacin
TCA (Imipramine, Doxepin)
Mirabegron
Overdose Ipecac
Paget’s Disease Alendronate
Colchicine
Etidronate
Pain Adjuvant Analgesics
Pain In Mouth Anesthetics (Mucosal-Local)
Panic Disorder Antidepressants, Tricyclic
Benzodiazepines
Monoamine Oxidase Inhibitors
Parasites Anthelmintics
Pentamidine
Parkinson’s Disease Antidyskinetics
Antihistamines
Antivirals for Influenza
Bromocriptine
Carbidopa and Levodopa
Levodopa
Orphenadrine
Pergolide
Selegiline
Tolcapone
Parkinson’s Tremors Antihistamines
Niacin
Pellagra
Peyronie’s Disease Aminobenzoate Potassium
Poisoning Charcoal Activated
Ipecac
Potassium Deficiency Potassium Supplements
Premature Labor Isoxsuprine
Ritodrine
Premenstrual Syndrome (PMS) Antidepressants, Tricyclic
NSAIDs
Buspirone
Calcium Supplements
Contraceptives, Oral and Skin
Danazol
Pyridoxine (Vitamin B-6)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Vitamin E
Pressure Sores Benzoyl Peroxide
Psoriasis Adrenocorticoids (Topical)
Anthralin
Biologics for Psoriasis
Calcipotriene
Coal Tar
Cyclosporine
Keratolytics
Methotrexate
Psoralens
Retinoids (Oral)
Retinoids (Topical)
Psychosis Thiothixene
Psychotic Disorders Aripiprazole
Carbamazepine
Clozapine
Haloperidol
Loxapine
Molindone
Olanzapine
Phenothiazines
Quetiapine
Risperidone
Thiothixene
Ziprasidone
Rectal Fissures Anesthetics (Rectal)
Respiratory Syncytial Virus (RSV) Ribavirin
Rickets Vitamin D
Rosacea Antibacterials (Topical)
Metronidazole
Azelaic Acid
Tetracyclines
Scabies Pediculicides
Schizophrenia Aripiprazole
Carbamazepine
Clozapine
Haloperidol
Molindone
Olanzapine
Phenothiazines
Quetiapine
Risperidone
Scleroderma Aminobenzoate Potassium
Shingles Antivirals (Topical)
Antivirals for Herpes Virus
Capsaicin
Sickle Cell Disease Hydroxyurea
Sinusitis Cephalosporins
Macrolide Antibiotics
Penicillins
Penicillins and Beta Lactamase Inhibitors
Sulfonamides
Tetracyclines
Trimethoprim
Xylometazoline
Skin Disorders (Rashes) Antibacterials (Topical)
Antibacterials, Antifungals (Topical)
Anesthetics (Topical)
Cyclophosphamide
Isotretinoin
Neomycin (Topical)
Retinoids (Topical)
Skin Lines and Wrinkles Botulinum Toxin (Type A)
Sleep Apnea Antidepressants, Tricyclic
Modafinil
Armodafinil
Progestins
Theophylline
Smoking Cessation Varenicline
Bupropion
Clonidine
Nicotine Transdermal Systems
Sore Throat Anesthetics (Mucosal-Local)
Medicated Lozenges, Sprays, Gargles
Stroke Prevention Platelet Inhibitors
Sunburn Adrenocorticoids (Topical)
Anesthetics (Topical)
Tonsillitis Cephalosporins
Macrolide Antibiotics
Tourette’s Syndrome Antidyskinetics
Haloperidol
Toxoplasmosis Pyrimethamine
Leucovorin
Atovaquone, Dapsone
Transplantation, Organ (Antirejection) Azathioprine
Cyclosporine
Immunosuppressive Agents
Tremors Benzodiazepines
Beta-Adrenergic Blocking Agents
Trigeminal Neuralgia Baclofen
Carbamazepine
Lamotrigine
Tuberculosis Cycloserine
Ethionamide
Isoniazid
Rifamycins
Ulcers Antacids
Anticholinergics
Bismuth Subsalicylate
Glycopyrrolate
Histamine H2 Receptor Antagonists
Metronidazole
Proton Pump Inhibitors
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Antidiabetes drugs

Antidiabetes Drugs; Indications, Side Effects, Drug Interactions

Antidiabetes drugs is used in diabetes treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, liraglutide and pramlintide, all are administered orally and are thus also called oral hypoglycemic agentsor oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected.

Diabetes mellitus type 2 is a disease of insulin resistance by cells. Type 2 diabetes mellitus is the most common type of diabetes. Treatments include (1) agents that increase the amount of insulin secreted by the pancreas, (2) agents that increase the sensitivity of target organs to insulin, and (3) agents that decrease the rate at which glucose is absorbed from the gastrointestinal tract.

List of Medications for Diabetes

  • Insulins
  • Insulin sensitizers (reduce insulin resistance)
    • Biguanides
    • Thiazolidinediones
  • Secretagogues (stimulate insulin release)
    • Sulfonylureas
    • Meglitinides
  • Agents that slow the digestive/absorptive process:
    • Alpha-Glucosidase Inhibitors
  • Glucagon-Like Peptide-1 (GLP-1) Agonists
  • Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
  • Amylin Analogues
  • Sodium-Glucose Transporter-2 (SGLT-2) Inhibitors
  • Combination Products

This comprehensive listing includes antihyperglycemic agents that can be used for glycemic control in diabetes.

New Antihyperglycemics

Class Generic/Brand/Approval year
SGLT-2 inhibitor Canagliflozin (Invokana), 2013
DPP-4 inhibitor Alogliptin (Nesina, Vipidia), 2013
SGLT-2 inhibitor Dapagliflozin (Farxiga), 2014
SGLT-2 inhibitor Empagliflozin (Jardiance), 2014
GLP-1 receptor agonist Albiglutide (Tanzeum), 2014
GLP-1 receptor agonist Dulaglutide (Trulicity), 2014
Inhaled insulin powder Afrezza, 2014

Insulin preparations differ in how quickly they work, when they peak maximal activity, and how long they work. Insulins are available for intravenous, intramuscular, and subcutaneous administration.

Generic Brand Name
Rapid Acting Insulins
Insulin aspart Novolog
Insulin glulisine Apidra
Insulin lispro Humalog
Insulin human Afrezza Inhalation Powder
Short Acting Insulins
Regular insulin Humulin R, Novolin R
Intermediate Acting Insulins
Insulin NPH Hagedorn NPH , Humulin N, Novolin N
Long Acting Insulins
Insulin detemir Levemir
Insulin glargine Lantus
Premixed Insulins
Insulin aspart protamine/
insulin aspart		 NovoLog 50/50, NovoLog 70/30
Insulin lispro protamine/
insulin lispro		 Humalog 50/50, Humalog 75/25
Combination with Insulins
Insulin glargine /Lixisenatide Soliqua 100/33
Insulin degludec/Liraglutide Xultophy 100/3.6

Sensitizers

Sensitizers increase the sensitivity of target organs to insulin.

Biguanides

Biguanides improve peripheral glucose uptake and utilization.

Generic Brand Name
Metformin Glucophage, Glucophage XR, Glumetza, Riomet, Fortamet

Phenformin and Buformin were withdrawn due to lactic acidosis risk.

Thiazolidinediones (Glitazones)

Thiazolidinediones work through the improvement of insulin sensitivity by acting on adipose, muscle, and liver to increase glucose utilization and decrease glucose production.

Generic Brand Name
Rosiglitazone Avandia
Pioglitazone Actos

Secretagogues

Secretagogues increase insulin secretion by the pancreas.

Sulfonylureas

Sulfonylureas stimulate insulin secretion by inhibiting the K(ATP) channel complex of the pancreatic beta cells. Sulfonylureas are used to treat type II diabetes. These agents are not indicated for type I diabetes.

Generic Brand Name
First-generation
Acetohexamide Dymelor
Chlorpropamide Diabinese
Tolazamide Tolinase
Tolbutamide Orinase
Second-generation
Glipizide Glucotrol, Minidiab, Glibenese
Glyburide (glibenclamide) Diabeta, Micronase, Glynase, Daonil, Euglycon
Glimepiride Amaryl
Gliclazide Uni Diamicron
Glyclopyramide Deamelin-S
Gliquidone Glurenorm

Meglitinides

Meglitinide derivatives stimulate insulin secretion from pancreatic cells, lowering blood glucose levels.

Generic Brand Name
Nateglinide Starlix
Repaglinide Prandin, NovoNorm

Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors are not technically glucose lowering agents because they do not have a direct effect on insulin secretion or sensitivity. These medications slow the digestive and absorptive process, preventing postprandial glucose raise.

Generic Brand Name
Acarbose Precose, Glucobay
Miglitol Glyset
Voglibose Basen

Glucagon-Like Peptide 1 (GLP-1) Agonists

GLP-1 analogs normalize fasting and postprandial blood glucose levels without causing hypoglycemia . Also, GLP-1 analogs reduce food intake and promote modest weight loss.

Generic Brand Name
Short-acting GLP-1 analogs
Exenatide Byetta
Lixisenatide Lyxumia, Adlyxin
Long-acting GLP-1 analogs
Liraglutide Victoza
Prolonged-acting GLP-1 analogs
Albiglutide Tanzeum
Dulaglutide Trulicity
Exenatide once weekly Bydureon
Under development
Taspoglutide Phase III clinical trials

Dipeptidyl Peptidase-4 Inhibitors (Gliptins)

Dipeptidyl peptidase-4 (DPP-4) inhibitors inhibit DPP-4, the enzyme that inactivates incretin hormones GLP-1 and GIP.

Generic Brand Name
Alogliptin Nesina, Vipidia
Anagliptin Suiny
Linagliptin Trajenta
Saxagliptin Onglyza
Sitagliptin Januvia
Teneligliptin Tenelia
DPP-4 inhibitors under development
Dutogliptin
Gemigliptin

Amylin Analogues

Pramlintide is a synthetic form of amylin, a pancreatic peptide produced by β-cells. Amylin and pramlintide lower postprandial glucose by lowering postprandial glucagon and delaying gastric emptying. Pramlintide is indicated for Type 1 and Type 2 diabetics who use insulin.

Generic Brand Name
Pramlintide Symlin

Sodium-Glucose Cotransporter 2 (SGLT-2) inhibitors

SGLT-2 inhibitors are a new class of drugs for Type 2 diabetes with novel mechanism of action. SGLT-2 inhibitors block reabsorption of glucose in the kidneys, leading to excretion of glucose in urine. These glucose lowering medications work independently of insulin.

Generic Brand Name
Canagliflozin Invokana
Dapagliflozin Forxiga, Farxiga
Empagliflozin Jardiance
SGLT-2 inhibitors under development
Ertugliflozin
Ipragliflozin
Remogliflozin etabonate
Tofogliflozin

Other Anti-diabetic Drugs

Generic Brand Name
Dopamine agonist
Bromocriptine Parlodel, Cycloset
Bile acid sequestrant
Colesevelam Welchol, Cholestagel, Lodalis

Combinations

Generic Brand Name
Alogliptin + Metformin Kazano
Dapagliflozin + Metformin Xigduo XR
Glipizide + Metformin Metaglip
Glyburide + Metformin Glucovance
Linagliptin + Metformin Jentadueto
Pioglitazone + Metformin Actoplus Met, Actoplus Met XR
Repaglinide + Metformin Prandimet
Rosiglitazone + Metformin Avandamet
Saxagliptin + Metformin Kombiglyze XR
Sitagliptin + Metformin Janumet
Rosiglitazone + Glimepiride Avandaryl
Pioglitazone + Glimepiride Duetact
Alogliptin + Pioglitazone Oseni
Simvastatin + Sitagliptin Juvisync
Empagliflozin + Metformin Synjardy

Mechanism of Action of antidiabetes drugs

Antidiabetes drugs mechanisms of action differ from other classes of oral antihyperglycemic agents. Antidiabetes drugs decreases blood glucose levels by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. These effects are mediated by the initial activation by  antidiabetes drugs of AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance, and the metabolism of glucose and fats. Activation of AMPK is required for antidiabetes drugs inhibitory effect on the production of glucose by liver cells. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors. Antidiabetes drugs administration also increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. The rare side effect, lactic acidosis, is thought to be caused by decreased liver uptake of serum lactate, one of the substrates of gluconeogenesis. In those with healthy renal function, the slight excess is simply cleared. However, those with severe renal impairment may accumulate clinically significant serum lactic acid levels. Other conditions that may precipitate lactic acidosis include severe hepatic disease and acute/decompensated heart failure.

Indications antidiabetes drugs

  • Diabetes, Type 2
  • Polycystic Ovary Syndrome
  • Diabetes, Type 3c
  • Insulin Resistance Syndrome
  • Female Infertility
  • For use as an adjunct to diet and exercise in adult patients (18 years and older) with NIDDM. May also be used for the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome (PCOS). Jentadueto is for the treatment of patients when both linagliptin and metformin is appropriate.

Side Effects of Antidiabetes Drugs

Most common

More common

Less common

  • Abnormal stools
  • bad, unusual, or unpleasant (after) taste
  • change in taste
  • difficulty with moving
  • discoloration of the fingernails or toenails
  • flu-like symptoms
  • joint pain
  • rash
  • runny nose
  • sneezing
  • stuffy nose
  • swollen joints

Drug Interactions of Antidiabetes Drugs

Antidiabetes drugs may interact with following drugs ,suppliments & may decrease the efficacy of drug

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