Promethazine

Class	H1 receptor antagonist
Chemistry	Phenothiazine
Routes of administration	Oral, IV, IM, s/c
Absorption	Well absorbed, but only 25% bioavailability due to vigorous first pass metabolism
Solubility	pKa 9.1, freely soluble in water
Distribution	VOD=30L/kg, 93% protein bound (mainly to albumin)
Metabolism	Undergoes extensive hepatic metabolism, mainly by CYP 2D6
Elimination	Clearance is almost completely hepatic; only some minimal amount is eliminated by the kidneys
Time course of action	Half-life 12-15 hours; duration of effect is 8-12 hours
Target receptor	All phenothiazines are competitive antagonists of multiple receptors: - Muscarinic (Gq-coupled) - Serotonin (many, including 5-HT3) - Dopamine (D2, Gi-protein-coupled) - Histamine (Gq-protein-coupled) - Adrenergic (alpha)
Mechanism of action	Multiple mechanisms of action: - Sedation is mainly due to the antihistamine effects - Antipsychotic effect is due to D2 dopamine receptor effect This is also responsible for the tardive dyskinesia - Undesirable side effects are mainly due to the antimuscarinic and antiadrenergic activity - Antiemetic mechanism is likely due to a combination of all of the receptor effects at the chemoreceptor trigger zone
Clinical effects	#NAME?
Literature reference	TGA document
CICM details of understanding	Level 3
Mentioned around Deranged Physiology	Classification of antiemetics
Related SAQs	Question 14 from the first paper of 2022 Question 23 from the first paper of 2016 Question 3 from the first paper of 2013 Question 17 from the second paper of 2012 Question 23 from the first paper of 2012 Question 10(p.2) from the first paper of 2010

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