Promethazine is a phenothiazide derivative with H1-receptor antagonist action. It acts by reversible, competitive inhibition of the interaction of histamine with H1 receptors. Histamines is released from mast cells on their encounter with antigens. It then binds to H1-receptors to initiate the typical symptoms of muscles and blood vessels to produce bronchospasm and flare, wheal and itch responses to antigens
Promethazine competes with histamine for there receptor sites to exert pronounced anti-muscarinic and anti-emetic effects. It inhibits the constrictor action of histamine on smooth muscles, especially respiratory muscles and blocks the action of histamine that results in capillary permeability and formation of oedema and wheal. It also binds to H1-receptors in the Central Nervous System, causing sedation.
Promethazine is well absorbed from the gastro-intestinal tract. Peak plasma concentrations have been observed 2 to 3 hours after administration by mouth, although there is low bioavailability due to high first pass metabolism in the liver.
Promethazine is widely distributed, it enters the brain and crosses the placenta. Values ranging from 76 to 93% have been reported to be plasma protein bound.
Promethazine undergoes extensive metabolism, predominantly to promethazine sulphoxide and also N-desmethylpromethazine sulphoxide. It is excreted slowly via urine and bile, chiefly as metabolites. Elimination half-lives of 5 to 14 hours have been reported
Promethazine hydrochloride is used for the symptomatic relief of hypersensitivity reactions including urticaria and angioedema, rhinitis and conjuctivitis and in pruritic skin conditions. It is also used for its anti-emetic action in the prevention and treatment of nausea and vomiting in conditions such as motion sickness, Meniere’s disease and other labyrinth disorders, drug induced vomiting and post-operative vomiting
It is also used pre-operatively in surgery and obstetrics for its sedative effects and for the relief of apprehension.
It may also be useful in night-time sedation
Dosage and administration
When used for motion sickness, promethazine should be given 30 minuutes to one hour or even 2 hours before starting the journey. Promethazine hydrochloride is usually given by mouth in a dose of 25 mg. This may be increased to 50 mg or 75 mg if required. It is commonly given at night because of its pronounced sedative effect. Alternatively up to 60 mg a day may be given in 2 to 4 divided doses. Higher or more frequent doses may be required for the treatment of nausea and vomiting. A dose of 25 mg at night may be used as hypnotic.
The side effects vary in incidence and severity with each patient. Central Nervous System depression effects include sedation, drowsiness, deep sleep, lassitude, dizzness and in-coordination. Paradoxical Central Nervous system stimulation particularly in children may occur with insomnia, nervousness, euphoria, convulsions. In high doses extrapyramidal symptoms may arise.
Antimuscarinic effects include dry mouth, thickened respiratory secretions and tightness of chest, blurred vision, urinary difficult and retention, constipation. Other gastrointestinal effects include vomiting, diarrhoea and epigastric pain.
Premature infants and neonates, patients with hypertension and blood disorders and known hypersensitivity to antihistamines
Caution is required when administering to elderly patients.
Caution is required in closed-angle glaucoma, urinary retention, prostatic hypertrophy, pyloroduodenal obstruction, epilepsy, severe cardiovascular disorders, liver disorders.
Promethazine may cause drowsiness. Patients should be warned not to drive or operate machinery if affected. Antihistamines may suppress positive skin test results and should be stopped several days before the test.
Antihistamines enhance the sedative effects of alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives, neuroleptics and should not be taken simultaneously.
Monoamine Oxidase Inhibitors, atropine and tricyclic antidepressants enhance the antimuscarinic effects of antihistamines.