Promethazine (Phenergan) is an oral, intramuscular (IM), rectal, and intravenous (albeit with caution!) phenothiazine derivative that is both a first-generation antihistamine (H1 receptor antagonism) and a weak typical antipsychotic (D2 receptor antagonism). It also demonstrates antagonism of muscarinic acetylcholine receptors (anticholinergic) and NMDA receptors (similar to ketamine), conferring some degree of analgesia too.

Given its broad receptor antagonism profile, promethazine is useful for allergies, motion sickness, to provide sedation, and what I use it for the most as a cardiothoracic anesthesiologist and intensivist – an antiemetic. While medications like ondansetron (Zofran) are good PROPHYLACTIC agents, if a patient is already vomiting, I think promethazine is a better option.

Side effects include respiratory depression, acute dystonia/tardive dyskinesia, confusion, dizziness, NMS, and rarely hypotension, bone marrow suppression, and seizures. If given intravenously (IV) as a push, extravasation can cause irreversible tissue damage. A Supreme Court case in 2009 related to improper IV injection leading to gangrene and subsequent amputation prompted the FDA to issue a black box warning recommending the IM route. Still, if the IV route is warranted, promethazine administration should not exceed the speed/concentration of a drip.

Drop me a comment below with your experiences regarding promethazine!

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