Brotizolam

Oral
Insomnia

Debiliated patients: 125 mcg at bedtime.

Acute pulmonary insufficiency, sleep apnoea syndrome, myasthenia gravis, psychoses, acute narrow-angle glaucoma. Severe hepatic impairment. Pregnancy and lactation.

Patient in whom a drop in BP might lead to cardiac complications; chronic pulmonary insufficiency. Prolonged use may cause dependence. Avoid abrupt withdrawal. Renal and mild to moderate hepatic impairment.

Paradoxical reactions (e.g. acute hyperexcitability, anxiety, hallucinations, increased muscle spasticity, rage, insomnia, sleep disturbances and stimulation); drowsiness, fatigue, ataxia; sedation and sleepiness, depression, lethargy, apathy, hypoactivity, lightheadedness, disorientation, restlessness, confusion, delirium, headache, slurred speech, dysarthria, syncope, vertigo, tinnitus, dizziness, nervousness, vivid dreams, psychomotor retardation; constipation, diarrhoea, dry mouth, nausea, vomiting, increased salivation; incontinence, dysuria, enuresis, changes in libido, urinary retention, menstrual irregularities; bradycardia, tachycardia, HTN, hypotension, palpitations; visual disturbances, diplopia; urticaria, pruritus, skin rash, dermatitis; hepatic dysfunction (e.g. hepatitis, jaundice), blood dyscrasias (e.g. agranulocytosis, anaemia, thrombocytopenia, eosinophilia).

May impair ability to drive or operate machinery.

Symptoms: Somnolence, confusion, coma, reduced or absent reflexes, resp depression, hypotension. Management: Induce vomiting if the patient is conscious; employ gastric lavage if unconscious. Supportive measures along w/ IV fluids should be employed. Maintain an adequate airway. May administer norepinephrine or metaraminol to treat hypotension or barbiturates if excitation occurs. Flumazenil may be useful as an antidote.

May potentiate the effect of centrally-acting drugs (e.g. neuroleptics, tranquilisers, antidepressants, hypnotics, antiepileptics, antihistamines, analgesics and anaesth). May increase the effect of muscle relaxants. Increased effect w/ CYP3A4 inhibitors (e.g. itraconazole, ketoconazole). Decreased effect w/ CYP3A4 inducers (e.g. carbamazepine, efavirenz).

Increased CNS effect w/ alcohol. Decreased effect w/ St John's wort.

Description:
Mechanism of Action: Brotizolam act as positive allosteric modulator on the γ-amino butyric acid (GABA)-A receptor. It binds to the pocket created by the α and γ subunits. This alteration, in turn, induces a conformational change in the GABA-A receptor's Cl channel that hyperpolarises the cell and accounts for GABA's inhibitory effect throughout the CNS.
Pharmacokinetics:
Absorption: Absorbed from the GI tract. Bioavailability: Approx 70%. Time to peak plasma concentration: 0.5-3 hr.
Distribution: Plasma protein binding: Approx 90%, to albumin.
Excretion: Via urine (approx 65%) and faeces (approx 22%). Half-life: 3.1-8.4 hr.

Source: National Center for Biotechnology Information. PubChem Database. Brotizolam, CID=2451, https://pubchem.ncbi.nlm.nih.gov/compound/Brotizolam (accessed on Jan. 22, 2020)

Hypnotics & Sedatives

N05CD09 - brotizolam ; Belongs to the class of benzodiazepine derivatives. Used as hypnotics and sedatives.

Griffin CE III, Kaye AM, Bueno FR et al. Benzodiazepine Pharmacology and Central Nervous System–Mediated Effects. The Ochsner Journal. 2013;13(2):214–223. Accessed 03/12/2014. PMID: 23789008

Anon. Brotizolam. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/12/2014.

Buckingham R (ed). Brotizolam. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/12/2014.