Diazepam

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

The main medical uses of diazepam include:

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

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 can be used to stop or reduce prolonged or recurrent attacks of epilepsy, including status epilepticus, which is a condition requiring immediate medical attention.
2. Antianxiolytic effect: Diazepam is used to reduce anxiety, panic attacks and other anxiety conditions.
3. Muscle spasms: The drug can be used to relieve muscle spasms, such as spastic conditions, muscle injuries or post-surgical conditions.
4. Sedation and stress relief before procedures: Diazepam can be used to provide sedation and relief of psychomotor agitation before 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 Treatment Procedures: The drug may 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 can have different dosages, usually from 2 mg to 10 mg.

Pharmacodynamics

1. Anxiolytic effects: 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 the amygdala, which is associated with the regulation of emotional responses.
2. Sedative effects: Diazepam has a sedative effect, which means it can cause relaxation, drowsiness and decreased agitation. This is also achieved by increasing inhibition in the central nervous system.
3. Muscle relaxant effect: Diazepam has the ability to reduce muscle tension and spasms. It is useful in treating conditions associated with muscle cramps or cramps.
4. Anticonvulsant effect: Diazepam is used to control seizure activity because it is able to suppress excitability in the central nervous system and prevent seizures.
5. Amnestic effects: 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 in the patient.

Pharmacokinetics

1. Absorption: Diazepam is usually well absorbed from the gastrointestinal tract after oral administration. Maximum plasma concentrations are usually achieved approximately 1-2 hours after administration.
2. Distribution: Diazepam is highly lipid-soluble and is therefore 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. Excretion: The half-life of diazepam from 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 administered 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 usually recommended to start with a dose of 5-15 mg at bedtime.
   • For children, the dose 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 the form of rectal suppositories to quickly relieve 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. Important points from the research:

1. Effects on Fetal Development: Studies in rats have shown that diazepam may cause changes in fetal development, including behavioral abnormalities in the offspring. This is due to its ability to penetrate the placental barrier and affect neuronal 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: Infants exposed to diazepam in utero have been observed to experience adjustment problems after birth, including worsening heart rate variability, which may indicate diazepam effects on the nervous system (Geijn et al., 1980).

Contraindications

1. Hypersensitivity: People with a 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 increased intraocular pressure or arc closure angle is present, diazepam should be avoided as it may cause increased intraocular pressure.
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 enhance its effects, so it should be used with caution.
6. Pregnancy and breast-feeding: The use of diazepam during pregnancy may be associated with risks to the development of the fetus. The drug is also excreted into breast milk and may affect breastfeeding.
7. Children: 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 depressive 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 decreased reaction time.
2. Decreased muscle tone and coordination: Diazepam can cause muscle weakness, as well as 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 impairment or difficulty concentrating with long-term use of diazepam.
5. Lower blood pressure: Diazepam may cause a decrease in blood pressure, which may result in dizziness or fainting.
6. Gastrointestinal disorders: Includes dry mouth, constipation, or diarrhea.
7. Dependence and withdrawal symptoms: With long-term use of diazepam, physical and mental dependence may develop, and discontinuation 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 general feeling of depression: The patient may experience deep sleepiness, decreased response to external stimuli, lethargy, and difficulty perceiving.
2. Respiratory depression: Respiration may slow to the point where the blood becomes insufficiently oxygenated.
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 lead to falls or loss of mobility.
5. Coma: In cases of severe overdose, a coma may develop.

Interactions with other drugs

1. Alcohol: Alcohol increases the effects of diazepam on the central nervous system, which can lead to 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. Mental health medications: Interactions between diazepam and antidepressants, antipsychotics, or other medications used to treat mental health conditions may result in increased or decreased effects of both diazepam and the other medications.
5. Drugs metabolized through cytochrome P450: Diazepam may affect the metabolism of some drugs metabolized through the cytochrome P450 system in the liver, which may alter their effectiveness and/or blood levels.