Diazepam

Diazepam is a drug that belongs to the benzodiazepine class and is widely used in medicine as an antiepileptic drug, sedative, muscle relaxant, and anxiolytic (anxiety-reducing drug).

Major medical uses of diazepam include:

1. Antiepileptic medication: Diazepam is often used to stop epileptic seizures, including status epilepticus, which is a severe and prolonged seizure.
2. Pre-procedural sedation: The drug may be used to provide sedation prior to surgical procedures, endoscopy, diagnostic procedures, and other medical interventions.
3. Muscle relaxation: Diazepam can be used to relieve muscle spasms and tension in a variety of conditions such as spastic conditions, muscle spasms and muscle tension syndromes.
4. Treatment of anxiety: Diazepam is one of the drugs used to reduce anxiety and relieve panic attacks and anxiety disorders.
5. Antidepressant treatment: Sometimes diazepam may be used as an adjunct in the treatment of depression, especially in cases where depression is accompanied by anxiety or anxiety disorders.

Diazepam is usually available as tablets for oral administration, as a solution for intravenous or intramuscular administration, and as rectangular granules for rectal administration.

Indications Diazepam

1. Epilepsy: Diazepam may be used to stop or reduce prolonged or recurring seizures of epilepsy, including status epilepticus, which is a condition that requires immediate medical attention.
2. Antianxiolytic action: Diazepam is used to reduce anxiety, panic attacks and other anxiety states.
3. Muscle spasms: The drug can be used to relieve muscle spasms, for example in spastic conditions, muscle injuries or postoperative conditions.
4. Pre-procedural sedation and anxiety relief: Diazepam may be used to provide sedation and relieve psychomotor agitation prior to surgical or diagnostic procedures.
5. Alcohol withdrawal syndrome: In cases of severe alcohol withdrawal syndrome, diazepam may be used to reduce symptoms of agitation, anxiety and delirium.
6. Respiratory distress syndrome: Diazepam can be used as a sedative and anxiolytic in patients with respiratory distress syndrome.
7. Diagnostic and therapeutic procedures: The drug can be used to provide sedation and reduce anxiety in patients during procedures such as endoscopy, colonoscopy, catheterization and others.

Release form

Tablets: This is one of the most common forms of diazepam. Tablets come in different strengths, usually from 2 mg to 10 mg.

Pharmacodynamics

1. Anxiolytic action: Diazepam has anxiolytic properties, which means it can reduce anxiety and tension. It achieves this by increasing the inhibition of activity in certain areas of the brain, especially in the amygdala, which is associated with the regulation of emotional responses.
2. Sedative effect: Diazepam has a sedative effect, which means that it is able to cause relaxation, drowsiness and decreased agitation. This is also achieved by increasing inhibition in the central nervous system.
3. Muscle relaxant action: Diazepam has the ability to reduce muscle tension and spasms. This is useful in treating conditions associated with muscle cramps or spasms.
4. Anticonvulsant action: Diazepam is used to control seizure activity because it is able to suppress excitability in the central nervous system and prevent seizures.
5. Amnestic action: Diazepam can cause temporary memory loss or amnesia, especially at high doses, making it useful in medical practice when performing procedures that may cause anxiety or discomfort to the patient.

Pharmacokinetics

1. Absorption: Diazepam is generally well absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are usually reached approximately 1-2 hours after administration.
2. Distribution: Diazepam is highly lipid soluble and therefore is well distributed throughout the body, including the brain and central nervous system (CNS).
3. Metabolism: Diazepam is metabolized in the liver to form several active metabolites, including desmethyldiazepam and oxazepam. They also have pharmacological activity.
4. Elimination: The half-life of diazepam in the body is about 20-100 hours depending on the metabolites. It is excreted primarily through the kidneys in the form of conjugates.

Dosing and administration

1. For anxiety disorders and seizures:

   • Adults are usually recommended to start with a dose of 2-10 mg per day, divided into several doses.
   • For children, the dose is usually calculated based on weight and age. Children are usually prescribed a dose of 0.1 to 0.3 mg/kg per day, also divided into several doses.
   • For seizures, diazepam can be used as an injection given by medical personnel.

2. For sedation and preoperative anesthesia:

   • For adults, the dose may vary from 5 to 20 mg, depending on individual sensitivity to the drug and the required level of sedation.
   • For children, the dosage is calculated depending on weight and age.

3. For the treatment of insomnia:

   • For adults, it is generally recommended to start with a dose of 5-15 mg at bedtime.
   • For children, the dosage is calculated individually depending on age and medical condition.

4. For the treatment of seizures in children with epilepsy:

   • Diazepam can also be used in rectal suppository form for rapid relief of seizures in children.

Use Diazepam during pregnancy

Using diazepam during pregnancy may be associated with some risks, especially if the drug is used in the first trimester or in high doses. Key points from the studies:

1. Effects on fetal development: Studies in rats have shown that diazepam can cause changes in fetal development, including behavioral abnormalities in the offspring. This is due to its ability to cross the placental barrier and affect neural development (Lyubimov et al., 1974).
2. Risk of birth defects: Although the overall risk of birth defects with diazepam has not been definitively established, there is evidence that its use may be associated with an increased incidence of certain abnormalities, such as congenital heart defects, if the drug is taken in high doses or in combination with other medications (Gidai et al., 2008).
3. Effects on neonates: There have been cases of infants exposed to diazepam in utero experiencing adjustment problems after birth, including decreased heart rate variability, which may indicate effects of diazepam on the nervous system (Geijn et al., 1980).

Contraindications

1. Hypersensitivity: People with known hypersensitivity to diazepam or other benzodiazepines should avoid its use.
2. Myasthenia gravis: This is an autoimmune disease characterized by weakening and fatigue of skeletal muscles. Diazepam may worsen the symptoms of this condition.
3. Glaucoma: If you have increased intraocular pressure or arc closure angle, diazepam should be avoided as it may cause increased pressure within the eye.
4. Respiratory depression: Diazepam can depress the respiratory center in the brain and is therefore contraindicated in acute respiratory failure.
5. Liver failure: In severe liver dysfunction, the drug may accumulate in the body and increase its effects, so it should be used with caution.
6. Pregnancy and breastfeeding: Use of diazepam during pregnancy may be associated with risk to fetal development. The drug is also excreted in breast milk and may affect breastfeeding.
7. Paediatric population: The use of diazepam in children may be contraindicated due to the risk of serious side effects.
8. Alcohol or drug poisoning: In these conditions, diazepam may enhance the depressant effect on the central nervous system.

Side effects Diazepam

1. Drowsiness and fatigue: This is one of the most common side effects of diazepam. Patients may experience drowsiness, decreased concentration, and poor reaction time.
2. Decreased muscle tone and coordination: Diazepam may cause muscle weakness and decreased coordination.
3. Dizziness and headache: Some patients may experience dizziness or headache while taking diazepam.
4. Memory loss: Some people may experience short-term memory loss or difficulty concentrating with long-term use of diazepam.
5. Low blood pressure: Diazepam may cause low blood pressure, which may result in dizziness or fainting.
6. Gastrointestinal disorders: Includes dry mouth, constipation or diarrhea.
7. Dependence and Withdrawal: With prolonged use of diazepam, physical and psychological dependence may develop, and withdrawal of the drug may cause withdrawal symptoms.
8. Allergic reactions: In rare cases, allergic reactions such as skin rash, itching, or swelling of the face may occur.

Overdose

1. Drowsiness and a general feeling of depression: The patient may experience profound drowsiness, decreased response to external stimuli, lethargy and difficulty perceiving.
2. Respiratory depression: Breathing may slow to the point where the blood is not getting enough oxygen.
3. Hypotension and Collapse: Low blood pressure can lead to collapse and loss of consciousness.
4. Decreased muscle tone: The patient may experience severe hypotonia and loss of muscle control, which may result in falls or loss of movement.
5. Coma: In case of severe overdose, coma may develop.

Interactions with other drugs

1. Alcohol: Alcohol increases the effects of diazepam on the central nervous system, which may result in increased muscle relaxation, sedation, and decreased coordination. This may increase the risk of accidents, especially when driving or performing other hazardous activities.
2. Other central depressants: Use of diazepam with other drugs such as opiates, barbiturates or hypnotics may result in increased central nervous system depression.
3. Pain medications: Some pain medications, such as opiates, may increase the effects of diazepam and increase the risk of side effects.
4. Drugs used to treat mental disorders: Interactions between diazepam and antidepressants, antipsychotics, or other drugs used to treat mental disorders may result in increased or decreased effects of both diazepam and the other drugs.
5. Drugs metabolised via cytochrome P450: Diazepam may affect the metabolism of some drugs metabolised via the cytochrome P450 system in the liver, which may alter their effectiveness and/or blood levels.