Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors
Mechanism of Action of Granisetron
Granisetron is a potent, selective antagonist of 5-HT3 receptors. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zoneThe drug is structurally and pharmacologically related to ondansetron, another selective inhibitor of 5-HT3 receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
Granisetron is a potent, selective antagonist of 5-HT3 receptors. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.
Indications of Granisetron
- Nausea Vomiting, Chemotherapy Induced
- Nausea Vomiting, Radiation Induced
- Nausea Vomiting, Postoperative
- Is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis
- Treatment of cyclic vomiting syndrome although there are no formal trials to confirm efficacy.
- Controlling post-operative nausea and vomiting
Indicated in adults for the prevention and treatment of acute nausea and vomiting associated with chemotherapy and radiotherapy.
Indicated in adults for prevention of delayed nausea and vomiting associated with chemotherapy and radiotherapy.
It is indicated in adults for the prevention of nausea and vomiting associated with moderately or highly emetogenic chemotherapy, for a planned duration of 3 to 5 consecutive days, where oral anti-emetic administration is complicated by factors making swallowing difficult.
- For the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy (including high dose cisplatin), postoperation, and radiation (including total body irradiation and daily fractionated abdominal radiation).
Contra Indications of Granisetron
- Low amount of magnesium in the blood
- Low amount of potassium in the blood
- Neuroleptic Malignant Syndrome
- Serotonin syndrome – adverse drug interaction
- Heart Muscle Disease caused by the Medication Doxorubicin
- Complete Heart Block
- Very Rapid Heartbeat – Torsades de Pointes
- Slow Heartbeat
- Prolonged QT interval on EKG
- Chronic heart failure
- Abnormal EKG with QT changes from Birth
- kidney disease with reduction in kidney function
- Allergies to Serotonin 5HT-3 Antagonists
Dosage of Granisetron
Nausea/Vomiting in Chemotherapy Induced
- IV: 10 mcg/kg over 5 minutes, beginning 30 minutes before initiation of chemotherapy.
- Orally: 2 mg, given up to 1 hour before chemotherapy, or 1 mg twice a day (the first dose is given up to 1 hour before chemotherapy, and the second dose is given 12 hours later).
Nausea/Vomiting in Postoperative
- IV: 1 mg undiluted over 30 seconds, given before induction of anesthesia, or immediately before reversal of anesthesia; or give after surgery.
Nausea/Vomiting in Radiation Induced
- slow or irregular heartbeat
2 mg orally given within 1 hour of radiotherapy.
Side Effects of Granisetron
The most common
- muscle twitching
- Any signs of infection, or a skin rash.
- Stomach pain, especially if it comes along with fever and diarrhea or constipation
- Yellowing of the skin or eyes
- Loss of appetite
- Chest pain or discomfort
- lightheadedness, dizziness, or fainting
- slow or irregular heartbeat
- unusual tiredness or weakness
- decrease in the amount of urine
- fast, pounding, or irregular heartbeat or pulse
- false sense of well-being
- increased watering of mouth
- vision changes;
- breast swelling (in men or women); or
- decreased sex drive, impotence, or difficulty having an orgasm.
- blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- restless muscle movements in your eyes, tongue, jaw, or neck;
- Drowsiness and lightheadedness the day after taking the medicine.
- Numbed emotions.
- Visual disturbances such as blurred vision or double vision.
- Shaky movements and unsteady walk (ataxia).
- Muscle weakness.
- Skin rashes.
- Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting or abdominal pain.
- Changes in sex drive.
- Low blood pressure (hypotension).
- Blood disorders.
- Unexpected aggression, restlessness or irritability .
- Nightmares or hallucinations
- behavioural changes, including aggressiveness, angry outbursts,
- increased trouble sleeping
- muscle spasms
- shortness of breath
- difficult or labored breathing
- difficulty with swallowing
- dizziness, faintness, or lightheadedness
- frequent urination
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blurred vision
- hives or welts, itching, or skin rash
- increased volume of pale, dilute urine
Drug Interactions of Granisetron
Granisetron may interact with following drugs, supplyments, & may change the efficacy of drugs
- antipsychotics (e.g. haloperidol, ziprasidone)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- beta-agonists (e.g., formoterol, salmeterol)
- corticosteroids (high dose; e.g., hydrocortisone, methylprednisolone, prednisone)
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, indapamide)
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- other serotonin receptor antagonists (e.g., granisetron, ondansetron)
- quinolone antibiotics (e.g., ciprofloxacin, levofloxacin)
- selective serotonin re-uptake inhibitors (SSRIs; e.g., citalopram, fluoxetine)
- tricyclic antidepressants (e.g., amitriptyline, imipramine, nortriptyline)
- tyrosine kinase inhibitors (e.g., nilotinib, sunitinib)
There are no available data on the use of granisetron in pregnant women; however, animal studies have revealed no teratogenic effects. Granisetron injection, patch, and oral formulations are classified as FDA pregnancy risk category B. It is not known if granisetron crosses the placenta; however, due to its low molecular weight, passage across the placental barrier is expected.
It is unknown whether granisetron or its metabolites are excreted in human milk. As a precautionary measure, breastfeeding should not be advised during treatment with Granisetron.