Promethazine

Promethazine has a variety of medical uses, including:

• Sedation[10]
• 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.[10]
• For moderate to severe morning sickness and hyperemesis gravidarum: In the UK, promethazine is drug of first choice, being preferred as an older drug with which there is a greater experience of use in pregnancy (second in line being metoclopramide or prochlorperazine).[11][10]
• For allergies such as hay fever and together with other medications in anaphylaxis[4]
• To aid with symptoms of the common cold[4]
• Motion sickness,[4] including space sickness[12]
• Hemolytic disease of the newborn[4]
• Anxiety before surgery[4]

Some documented side effects include:

• Tardive dyskinesia, pseudoparkinsonism, acute dystonia (effects due to dopamine D2 receptor antagonism)[10]
• Confusion in the elderly[10]
• Drowsiness, dizziness, fatigue, more rarely vertigo
• Known to have effects on serotonin and dopamine receptors.[13]
• Dry mouth[10]
• Nausea[14]
• Respiratory depression in patients under age of two and in those with severely compromised pulmonary function[15]
• Blurred vision, xerostomia, dry nasal passages, dilated pupils, constipation, and urinary retention. (due to cholinergic effects)[10]
• Chest discomfort/pressure (In children less than 2 years old)[10]
• Akathisia[16]

Less frequent:

• Cardiovascular side effects to include arrhythmias and hypotension[10]
• Neuroleptic malignant syndrome[10]
• Liver damage and cholestatic jaundice[10]
• Bone marrow suppression, potentially resulting in agranulocytosis, thrombocytopenia, and leukopenia[10]
• Depression of the thermoregulatory mechanism resulting in hypothermia/hyperthermia[10]

Rare side effects include:

• Seizures[10]

Because of potential for more severe side effects, this drug is on the list to avoid in the elderly.[17] 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.[18]

Promethazine is listed as one of the drugs of highest anticholinergic activity in a study of anticholinergenic burden, including long-term cognitive impairment.[19]

Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects.[2] It acts primarily as a strong antagonist of the H₁ receptor (antihistamine, K_i = 1.4 nM[20]) and a moderate mACh receptor antagonist (anticholinergic),[2] and also has weak to moderate affinity for the 5-HT_2A,[21] 5-HT_2C,[21] D₂,[22][23] and α₁-adrenergic receptors,[24] 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; which might promote sedation in addition with the strong antihistaminergic effects of the H₁ receptor, but also as a weaker analgesic. It does not however affect the AMPA receptors.[25]

Another notable use of promethazine is as a local anesthetic, by blockage of sodium channels.[24]

Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the early 1940s.[27] The team was seeking to improve on diphenhydramine; the same line on medical chemistry led to the creation of chlorpromazine.[28]

As of July 2017 it was 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, Xepagan, Zinmet, and Zoralix.[1]

Atosil syrup

It is also marketed in many combination drug formulations:

• with carbocisteine as Actithiol Antihistaminico, Mucoease, Mucoprom, Mucotal Prometazine, and Rhinathiol;
• with paracetamol (acetaminophen) as Algotropyl, Calmkid, Fevril, Phen Plus, and Velpro-P;
• with paracetamol and dextromethorphan as Choligrip na noc, Coldrex Nočná Liečba, Fedril Night Cold and Flu, Night Nurse, and Tachinotte;
• with paracetamol, phenylephrine, and salicylamide as Flukit;
• with dextromethorphan as Axcel Dextrozine and Hosedyl DM;
• with dextromethorphan and ephedrine as Methorsedyl;
• with dextromethorphan and pseudoephedrine as Sedilix-DM;
• with dextromethorphan and phenylephedrine as Sedilix-RX;
• with pholcodine as Codo-Q Junior and Tixylix;
• with pholcodine and ephedrine as Phensedyl Dry Cough Linctus;
• with pholcodine and phenylephedrine as Russedyl Compound Linctus;
• with pholcodine and phenylpropanolamine as Triple 'P';
• with codeine as Kefei and Procodin;
• with codeine and ephedrine as Dhasedyl, Fendyl, and P.E.C.;
• with ephedrine and dextromethorphan as Dhasedyl DM;
• with glutamic acid as Psico-Soma, and Psicosoma;
• with noscapine as Tussisedal; and
• with chlorpromazine and phenobarbital as Vegetamin.[1]

• "Promethazine". U.S. National Library of Medicine and National Institutes of Health.