Alprazolam

Introduction

Alprazolam is a short-acting benzodiazepine. It is used in the short-term treatment of anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD). GAD improvement occurs generally within a week. Alprazolam is generally taken by mouth.

Pronunciation

Alprazolam 0.25mg (XANAX)

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Alprazolam Tablet 0.25 mg	ALPR01	DDA
Alprazolam Tablet 0.5 mg	ALPR02	DDA

Mechanism of Action

• Alprazolam is a benzodiazepine.
• Gama-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, acting on the GABA receptors in the central nervous system (CNS), thus inhibiting the nerve impulses.
• Alprazolam acts on the benzodiazepine receptors in the brain and the spinal cord. Benzodiazepine receptors in the CNS are linked with GABA receptors as a complex.
• Alprazolam by binding to the benzodiazepine receptors results in activation of the GABA-benzodiazepine receptor complex, resulting in inhibition of nerve impulses, overall depression of brain and spinal cord.
• Thus alprazolam use helps to promote muscle relaxation, reduce anxiety, control of convulsions and promote sleep.

Dosage

Short-term use in anxiety	By mouth ADULT: 250 – 500 micrograms 3 times a day, increased if necessary, every 3 to 4 days, up to 3 mg daily. ELDERLY: 250 micrograms 2 – 3 times a day DEBILITATED PATIENTS: 250 micrograms 2 – 3 times a day

Side Effects

Sedative drugs, including alprazolam, have been associated with an increased risk of death.

Possible side effects include:

Very common (>10% of incidence) or Common (1-10% of incidence)	Amnesia失憶and concentration problems Ataxia (especially in the elderly) Confusion (especially in the elderly) Dependence Drowsiness the next day Muscle weakness Paradoxical increase in aggression
Infrequent (0.1 -1% of incidence)	Dizziness Dysarthria Gastro-intestinal disturbances Gynecomastia headache Hypotension Incontinence Urinary retention, constipation Slurred speech Tremor Vertigo Visual disturbances
Rare (<0.1% of incidence)	Apnoea窒息 Blood disorder Jaundice Respiratory depression hypersensitivity reactions

Overdosage can produce CNS depression and coma.

Paradoxical reactions

Although unusual, the following paradoxical reactions have been shown to occur:

• aggression
• mania, agitation, and restlessness
• rage
• twitches and tremor

Pharmacokinetics

Oral bioavailability	Pregabalin is well absorbed after oral doses.
Onset of action	Peak plasma concentrations occur within 1 to 2 hours of a dose.
Metabolism	Alprazolam is metabolized in the liver, mainly by the cytochrome P450 isoenzyme CYP3A4.
Elimination half-life	Alprazolam is eliminated in the urine. The mean elimination half-life is 11 to 15 hours.

Drug Management

Monitoring

• changes in mood, the development or worsening depression, and/or any thoughts or behaviour of suicide.
• Fall prevention in elderly patients

Dependence and Withdrawal

Dependence is particularly likely in patients with a history of alcohol or drug abuse and in those with marked personality disorders. Alprazolam should therefore be withdrawn by gradual reduction of the dose after regular use for even a few weeks; the time needed for withdrawal cab vary from about 4 weeks to a year or more.

Drug interaction

Enhanced sedation or respiratory and cardiovascular depression may occur if alprazolam is given with other drugs that have CNS-depressant properties; these include alcohol, antidepressants, sedative antihistamines, antipsychotics, and opioid analgesics. Alprazolam is primarily metabolized via CYP3A4. Combining CYP3A4 inhibitors such as cimetidine, erythromycin, and itraconazole delay the hepatic clearance of alprazolam, which may result in its accumulation and increased severity of its side-effects.