Diazepam is a benzodiazepine derivative with anti-anxiety, sedative, hypnotic and anticonvulsant properties. Diazepam potentiates the inhibitory activities of gamma-aminobutyric acid (GABA) by binding to the GABA receptor, located in the limbic system and the hypothalamus. This increases the frequency of chloride channel opening, allowing the flow of chloride ions into the neuron and ultimately leading to membrane hyperpolarization and a decrease in neuronal excitability.
A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. It is used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome
Mechanism of Action of Diazepam
Benzodiazepines bind nonspecifically to benzodiazepine receptors which mediate sleep, affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
Indications of Diazepam
- Anxiety
- Alcohol withdrawal
- trouble sleeping, and restless legs syndrome.
- It may also be used to cause memory loss during certain medical procedures
- Borderline personality disorder
- Endoscopy or radiology premedication
- Muscle spasm
- Hyperekplexia
- ICU agitation
- Light anesthesia
- Light sedation
- Meniere’s disease
- Night terrors
- Seizure prevention
- Seizures
- Status epilepticus
- Temporomandibular joint disorder
- Hypnotic disorder in the short-term management of insomnia, as a sedative and premedicant,
- Anticonvulsant
- Anxiety disorders
- Refractory epilepsy
- Refractory seizure disorders
- Skeletal muscle spasm
- Adjunctive treatment of spastic muscular paresis (paraplegia/tetraplegia) caused by cerebral or spinal cord conditions such as stroke, multiple sclerosis, or spinal cord injury (long-term treatment is coupled with other rehabilitative measures)
- Palliative treatment of stiff person syndrome
- Pre- or postoperative sedation, anxiolysis or amnesia (e.g., before endoscopic or surgical procedures)
- Treatment of complications with a hallucinogen crisis and stimulant overdoses and psychosis, such as LSD, cocaine, or methamphetamine
- Preventative treatment of oxygen toxicity during hyperbaric oxygen therapy
Contra-Indications of Diazepam
- low amount of albumin proteins in the blood
- Alcohol Intoxication
- drug abuse
- Depression
- Myasthenia Gravis
- Wide-Angle Glaucoma
- closed angle glaucoma
- Severe Chronic Obstructed Lung Disease
- Decreased Lung Function
- Lung Disease
- Liver Problems
- Severe Liver Disease
- Severe Renal Impairment
- Temporarily Stops Breathing While Sleeping
- Pregnancy
- A Mother who is Producing Milk and Breastfeeding
Dosage of Diazepam
Strengths: 2 mg, 2.5 mg 5 mg, 10 mg, 15 mg, 20 mg, 5 mg/5 mL, 5 mg/mL;
Anxiety
- 2 to 10 mg orally 2 to 4 times a day
Parenteral
- Moderate Anxiety Disorders and Symptoms: 2 to 5 mg IM or IV, repeated in 3 to 4 hours if necessary
- Severe Anxiety Disorders and Symptoms: 5 to 10 mg IM or IV, repeated in 3 to 4 hours if necessary
Muscle Spasm
- 2 to 10 mg orally 3 to 4 times a day
Parenteral
- 5 to 10 mg IM or IV, then 5 to 10 mg IM or IV in 3 to 4 hours if necessary
Alcohol Withdrawal
- Initial dose: 10 mg orally 3 to 4 times a day for the first 24 hours
- Maintenance dose: 5 mg orally 3 to 4 times a day as needed
Parenteral
- 10 mg IM or IV once, then 5 to 10 mg IM or IV in 3 to 4 hours if necessary
Seizures
- 2 to 10 mg orally 2 to 4 times a day
Rectal
- Initial dose: 0.2 mg/kg rectally, rounded upward to the next available dose. A 2.5 mg rectal dose may be given as a partial replacement if patients expel a portion of the initial dose
- If necessary, a second dose of 0.2 mg/kg may be given rectally 4 to 12 hours after the first dose.
- Maximum Frequency: May be used to treating up to 1 seizure episode every 5 days, and no more than 5 episodes/month
Endoscopy or Radiology Premedication
- Cardioversion: 5 to 15 mg IV once 5 to 10 minutes before the procedure
Endoscopic Procedures
- IV: Usually less than 10 mg, but some patients require up to 20 mg IV, especially when narcotics are omitted
- IV titration: The IV dose should be titrated to desired sedative response (e.g., slurring of speech) with slow administration immediately before the procedure.
- IM: 5 to 10 mg IM once 30 minutes prior to the procedure
Status Epilepticus
Parenteral
- Initial dose: 5 to 10 mg IV once, repeated at 10 to 15-minute intervals to a maximum dose of 30 mg if necessary
Side Effects of Diazepam
The most common
- Irritability and aggression
- Drowsiness
- Dry mouth
- Abdominal or stomach pain
- cold or flu symptoms such as stuffy nose, sore throat, fever;
- Constipation
- dizziness or lightheadedness
- blurred vision
- hiccups
- coughing
- pain, redness, or hardening of the skin at the injection site
- Nausea, vomiting,
- painful or swollen gums
- numbness or heavy feeling in the jaw
- stomach pain,
- a headache,
- reversible hair loss or thinning, and
- fever
Common
- chills or fever
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in chest
- excessive sweating
- sudden drowsiness or need to sleep
- coughing up blood
- liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite,
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- hallucinations
- a headache
- irritability
- lightheadedness
- cold and clammy skin
- fast and shallow breathing
- swelling of your feet, legs, or hands purple spot on your skin caused by internal bleeding
- fast or abnormal heart rate or palpitations
- loss of appetite
- lower back, side, or stomach pain
- mental depression
- muscle pain or cramps
- Swelling of your feet or ankles
- Shortness of breath
- Nausea, fever, dark urine, loss of appetite
- Depression
- Ataxia
- Somnolence (difficulty staying awake)
- Mental confusion
- Hypotension
- Respiratory arrest
- Vasomotor collapse
Drug Interactions of Diazepam
Diazepam may interact with following drugs, supplements, & may change the efficacy of drugs
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- aripiprazole
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- baclofen
- barbiturates (e.g., butalbital, phenobarbital)
- benzodiazepines (e.g.diazepam, lorazepam)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- estradiol (birth control pills)
- gabapentin
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- mirtazapine
- Oral contraceptives (birth control pills)
- muscle relaxants
- phenytoin
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- quinolone antibiotics (e.g., ciprofloxacin, ofloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- tapentadol
- theophylline
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
Pregnancy & Lactation of Diazepam
FDA Pregnancy Category D
Pregnancy
You should not take Diazepam tablets if you are pregnant, planning to become pregnant or are breastfeeding. If you take Diazepam tablets late in your pregnancy or during labor your baby might have a low body temperature, floppiness, and breathing difficulties. If taken regularly during late pregnancy, your baby may develop withdrawal symptoms. Ask your doctor or pharmacist for advice before taking any medicine.
Breastfeeding
The milk to plasma ratio ranged between 0.2 and 2.7. This drug may accumulate in breastfed infants, especially with repeated dosing or with acute use of rectal gel formulations.
Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk.
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