Alprazolam

Products

Alprazolam is commercially available as tablets, sustained-release tablets, and sublingual tablets (Xanax, generics). It has been approved in many countries since 1980. “Xanax” is a palindrome and remains the same when read forwards or backwards.

Structure and properties

Alprazolam (C17H13ClN4, Mr = 308.7 g/mol) exists as a white crystalline powder that is practically insoluble in water. It is a 1,4-triazole benzodiazepine and differs from the classical benzodiazepines in having a triazole ring in the molecule.

Effects

Alprazolam (ATC N05BA12) has antianxiety, disinhibitory, depressant, antidepressant, and partial euphoric properties. It crosses the blood–brain barrier and binds in the brain to the GABAA receptor. It thereby enhances the effect of the inhibitory neurotransmitter GABA in the central nervous system. The half-life is between 12 to 15 hours.

Indications

For the treatment of anxiety and panic disorders.

Dosage

According to the professional information. The usual daily dose is 0.5 to 4 mg divided into several administrations. A daily dose of 6 mg should not be exceeded. Slow-release medications are also available, which are taken once or twice daily. Discontinuation after regular dosing must be gradual, as discontinuation can lead to withdrawal symptoms.

Abuse

Because of its antianxiety, disinhibitory, depressant, and sometimes euphoric effects, alprazolam, like other benzodiazepines, is abused. Many celebrities are said to have (over)used alprazolam. According to the autopsy report, actor Heath Ledger (, ) died from a drug cocktail that contained alprazolam in addition to opioids, benzodiazepines and doxylamine. Michael Jackson is said to have consumed alprazolam in high doses, and Whitney Houston also had the substance in her blood when she died. The death of rapper Lil Peep is attributed to an overdose of alprazolam and fentanyl. Several other opioids and narcotics were found during his autopsy.

Contraindications

  • Hypersensitivity
  • Myasthenia gravis
  • Severe respiratory insufficiency
  • Sleep apnea syndrome
  • Concurrent administration of HIV protease inhibitors.

For complete precautions, see the drug label. Alprazolam can lead to dependence, especially with prolonged use, high dosage and predisposition. It should be taken short-term and sporadically if possible, and the need for treatment should be reviewed regularly.

Interactions

Alprazolam is biotransformed by CYP3A4 to inactive hydroxy derivatives. CYP3A4 inhibitors such as azole antifungals or marcolides may result in increased concentrations and prolonged effects. For this reason, concomitant administration of HIV protease inhibitors is also contraindicated. Other appropriate interactions must be considered.

Adverse effects.

  • Drowsiness, fatigue, dizziness, lightheadedness.
  • Blurred vision, headache, depression, sleep disturbances, nervousness, anxiety, tremor, weight changes, memory impairment, anterograde amnesia, incoordination
  • Gastrointestinal complaints
  • Allergic reactions
  • Dystonia, irritability, anorexia, fatigue, articulation difficulties, jaundice, muscle weakness, changes in libido, menstrual irregularities, incontinence, urinary retention, liver dysfunction, hyperprolactinemia.
  • Rare: Paradoxical reactions such as difficulty concentrating, confusion, hallucinations, adverse behavioral reactions such as irritability and aggressive behavior.

Withdrawal

With abrupt discontinuation after regular use, withdrawal symptoms occur. Alprazolam should therefore be discontinued gradually through a gradual dose reduction. Withdrawal symptoms include: Tremors, restlessness, sleep disturbances, anxiety, mental upset, headache, poor concentration, sweating, muscle and abdominal cramps, perceptual disturbances. Rare: Delirium, cerebral seizures.