MarketPromethazine
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Promethazine

Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, nausea, and vomiting. It may also help with some symptoms associated with the common cold and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use. Promethazine is taken by mouth (oral), as a rectal suppository, or by injection into a muscle (IM).

Medical uses
25mg tablets Promethazine has a variety of medical uses, including: • Sedation • For nausea and vomiting associated with anesthesia or chemotherapy. It is commonly used postoperatively as an antiemetic. The antiemetic activity increases with increased dosing; however, side effects also increase, which often limits maximal dosing. • For allergies such as hay fever and together with other medications in anaphylaxisHemolytic disease of the newbornAnxiety before surgery ==Side effects==
Side effects
Some documented side effects include: • Tardive dyskinesia, pseudoparkinsonism, acute dystonia (effects due to dopamine D2 receptor antagonism) • Dry mouth • Respiratory depression in patients under the age of two and those with severely compromised pulmonary function • Blurred vision, xerostomia, dry nasal passages, dilated pupils, constipation, and urinary retention. (due to its anticholinergic effects) Less frequent: • Cardiovascular side effects to include arrhythmias and hypotension In many countries (including the US and UK), promethazine is contraindicated in children less than two years of age, and strongly cautioned against in children between two and six, due to problems with respiratory depression and sleep apnea. Promethazine is listed as one of the drugs with the highest anticholinergic activity in a study of anticholinergic burden, including long-term cognitive impairment. ==Overdose==
Overdose
Promethazine in overdose can produce signs and symptoms including CNS depression, hypotension, respiratory depression, unconsciousness, and sudden death. Other reactions may include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes. Atypically and/or rarely, stimulation, convulsions, hyperexcitability, and nightmares may occur. Anticholinergic effects like dry mouth, dilated pupils, flushing, gastrointestinal symptoms, and delirium may occur as well. Treatment of overdose is supportive and based on symptoms. ==Pharmacology==
Pharmacology
Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects. Despite structural differences, promethazine exhibits a strikingly similar binding profile to promazine, another phenothiazine compound. Both promethazine and promazine exhibit comparable neuroleptic potency, with a neuroleptic potency of 0.5. However, dosages used therapeutically, such as for sedation, have no antipsychotic effect. It acts primarily as a strong antagonist of the H1 receptor (antihistamine, Ki = 1.4 nM) and a moderate mACh receptor antagonist (anticholinergic), 5-HT2C, and α1-adrenergic receptors, where it acts as an antagonist at all sites, as well. New studies have shown that promethazine acts as a strong non-competitive selective NMDA receptor antagonist, with an EC50 of 20 μM; Another notable use of promethazine is as a local anesthetic, by blockage of sodium channels. ==Chemistry==
Chemistry
Solid promethazine hydrochloride is a white to faint-yellow, practically odorless, crystalline powder. Slow oxidation may occur upon prolonged exposure to air, usually causing blue discoloration. Its hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers. ==History==
History
Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the 1940s. The team was seeking to improve on diphenhydramine; the same line of medical chemistry led to the creation of chlorpromazine. ==Society and culture==
Society and culture
As of July 2017, it is marketed under many brand names worldwide: Allersoothe, Antiallersin, Anvomin, Atosil, Avomine, Closin N, Codopalm, Diphergan, Farganesse, Fenazil, Fenergan, Fenezal, Frinova, Hiberna, Histabil, Histaloc, Histantil, Histazin, Histazine, Histerzin, Lenazine, Lergigan, Nufapreg, Otosil, Pamergan, Pharmaniaga, Phenadoz, Phenerex, Phenergan, Phénergan, Pipolphen, Polfergan, Proazamine, Progene, Prohist, Promet, Prometal, Prometazin, Prometazina, Promethazin, Prométhazine, Promethazinum, Promethegan, Promezin, Proneurin, Prothazin, Prothiazine, Prozin, Pyrethia, Quitazine, Reactifargan, Receptozine, Romergan, Sominex, Sylomet, Vertigon, Xepagan, Zinmet, and Zoralix. Product liability lawsuit In 2009, the US Supreme Court ruled on a product liability case involving promethazine. Diana Levine, a woman with a migraine, was administered Wyeth's Phenergan via IV push. The drug was injected improperly, resulting in gangrene and subsequent amputation of her right forearm below the elbow. A state jury awarded her $6 million in punitive damages. The case was appealed to the Supreme Court on grounds of federal preemption and substantive due process. The Supreme Court upheld the lower courts' rulings, stating that "Wyeth could have unilaterally added a stronger warning about IV-push administration" without acting in opposition to federal law. In effect, this means drug manufacturers can be held liable for injuries if warnings of potential adverse effects, approved by the US Food and Drug Administration (FDA), are deemed insufficient by state courts. In September 2009, the FDA required a boxed warning be put on promethazine for injection, stating the contraindication for subcutaneous administration. The preferred administrative route is intramuscular, which reduces the risk of surrounding muscle and tissue damage. == References ==
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