Study about (Alprazolam)

Alprazolam  

Alprazolam is a medication classified as a benzodiazepine, primarily prescribed to address anxiety and panic disorders.

It exerts its effects by modulating the activity of neurotransmitters in the brain, particularly gamma-aminobutyric acid (GABA), leading to a calming and relaxing influence on the central nervous system.

 What to learn?

·    Clinical uses

·    Dosage

·    Mechanism of action

·    Absorption

·    Metabolism

·    Half-life

·    Route of administration

·    Contraindication

·    Side effects

·    Toxicity

Clinical uses

·    Alprazolam is often prescribed for generalized anxiety disorder (GAD).

·    It may be used to manage symptoms of social anxiety disorder.

·    Alprazolam is effective in the treatment of panic disorder with or without agoraphobia.

·    Sometimes, it may be used as a short-term treatment for insomnia.

·    It might be part of a treatment plan for certain medical conditions where anxiety plays a significant role.

Dosage

Anxiety disorder:

·    Adult: PO 0.25-0.5 MG t.i.d.

                (max: 4mg/d);

·    Geriatric: PO 0.125-0.25 mg b.i.d.

Panic Attacks:

·    Adult: PO 1-2 mg t.i.d.

                      (max: 8mg/d);

Mechanism of action

·    Alprazolam is a triazolobenzodiazepine used to treat certain anxiety and panic disorders. Alprazolam acts on benzodiazepine receptors BNZ-1 and BNZ-2. The active metabolites 4- hydroxyalprazolam acts on these receptors with 0.20 times the potency of alprazolam and alpha-hydroxyalprazolam acts on these receptors with 0.66 times the potency.

·    The effect of alprazolam on BNZ-1 mediates the sedation and anti-anxiety effects of the drug while the action on BNZ-2 mediates effects on memory, coordination, muscle relaxation, and anticonvulsive activity.

·    Alprazolam also couple with GABA-A receptors to enhance GABA binding to its receptor. This interaction mediates inhibition of the nervous system and results in a calming effect.

Absorption

·    Oral bioavailability of a standard release tablet of alprazolam is 84-91% with a time to maximum concentration of 1.8 hours.

 

·    A 1mg oral dose of alprazolam leads to a maximum plasma concentration of 12-22mcg/L.

 

·    Alprazolam is rapidly absorbed in the gastrointestinal tract.

Metabolism

·    Alprazolam is metabolized to less effective metabolites by various CYPs includin, CYP3A4, CYP3A5, CYP3A7, and CYP2C9.

·    The majority of alprazolam metabolism is mediated by hydroxylation vi CYP3As. 4-hydroxyalprazolam has 20% the binding affinity of the parent drug alpha-hydroxy alprazolam has 66% the affinity, and the benzophenone metabolite has <1% affinity.

Half-Life

·    The half-life is 16.3h in the elderly,

• 5.8-65.3h in patients with alcoholic liver disease,

• 9.9-40.4h in obese patients.

• The half-life is 25% higher in Asian patients compared to Caucasians.

• Other studies have shown the half-life to be 9-16h.

Rout of administration

·    Alprazolam is mainly eliminated in the urine.

 

·    A large portion of the dose is eliminated as unmetabolized alprazolam.

 

·    10% of the dose is eliminated as alpha-hydroxy-alprazolam and 4- hydroxy-alprazolam.

 Contraindication

·    Acute alcohol intoxication with depressed vital signs,

·    acute angle closure glaucoma,

·    myasthenia gravis,

·    severe COPD,

·    hypersensitivity,

·    pregnancy and lactation.

Side effects

·    Frequent: Ataxia, light- headedness, transient mild somnolence, slurred speech.

·    Occasional: Confusion, depression, blurred vision, constipation, diarrhoea, dry mouth, headache nausea.

·    Serious reactions: abrupt or too rapid withdrawal may result in

·    pronounced restlessness, irritability, insomnia, hand tremors, abdominal and muscle cram, diaphoresis, vomiting and seizures. Over dose results in somnolence, confusion, diminished reflexes and coma.

Toxicity

·    Alprazolam overdose can present as sleepiness, confusion, poor coordination, slow reflexes, coma, and death.

·    Taking alprazolam with alcohol lowers the threshold for overdose.

·    Patients should have their respiration, pulse, and blood pressure monitored.

·    Patients can be treated by gastric lavage and intravenous fluids.

·    If hypotension occurs, patients may be treated with vasopressors.

·    In known, or suspected overdoses, patients can be given the benzodiazepine receptor antagonist flumazenil in addition to other methods of management.

·    Alprazolam is a pregnancy category D teratogen meaning there is evidence of risk to the fetus of a mother taking alprazolam but in some cases the benefit may outweigh the risk.

·    Children born to these mothers are also at risk of withdrawal symptoms, flaccidity, and respiratory issues.

·    Benzodiazepines are expressed in human breast milk and so nursing is generally not recommended in mothers taking alprazolam.

·    Alprazolam is not associated with carcinogenicity, mutagenicity, or impairment of fertility.