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Pharmacology: Pharmacodynamics: Promethazine: H1 antihistamine, phenothiazine with an aliphatic side chain, characterized by: A marked sedative effect at standard doses as a result of histaminergic and adrenolytic activity; An anticholinergic effect causing peripheral adverse effects; A peripheral adrenolytic effect, possibly affecting hemodynamics (risk of postural hypotension).
All antihistamines are opposed to the effects of histamines, particularly on the skin, bronchi, intestine and blood vessels, through more or less reversible competitive antagonism.
Most have an antitussive effect, which is mild in itself but potentiates the effects of central morphine antitussives as well as those of other bronchodilators such as sympathomimetic amines, with which they are often combined.
Pharmacokinetics: Orally administered carbocisteine is rapidly absorbed; peak plasma concentration is reached within two hours. Bioavailability is low (less than 10% of the dose administered), probably because of intraluminal metabolism and a marked hepatic first-pass effect. Elimination half-life is approximately two hours. Carbocisteine and its metabolites are eliminated primarily in the urine.
Promethazine bioavailability is from 13 to 40%. Peak plasma concentrations are reached within 1.5 to 3 hours. The volume of distribution is high, due to the liposolubility of the drug (approximately 15 L/kg). Promethazine is 75-80% bound to plasma proteins. The elimination half-life is from 10 to 15 hours. Metabolism consists of sulfoxidation followed by demethylation. Renal clearance accounts for less than 1% of total clearance, and approximately 1% of administered promethazine is excreted unchanged in the urine. The metabolites recovered in the urine, particularly sulfoxide, account for approximately 20% of the dose.
Physiopathological variation: risk of accumulation of antihistamines in patients with kidney or liver insufficiency.
