Promethazine

Promethazine
Systematic (IUPAC) name
N, N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine
Identifiers
CAS number	60-87-7
ATC code	D04AA10 R06AD02, R06AD05
PubChem	4927
DrugBank	APRD00601
Chemical data
Formula	C17H20N2S
Mol. mass	284.425 g/mol
Pharmacokinetic data
Bioavailability	88% absorbed but after first-pass metabolism reduced to 25% absolute bioavailability
Protein binding	93%
Metabolism	Hepatic glucuronidation and sulfoxidation
Half life	16-19 hours
Excretion	Renal and biliary
Therapeutic considerations
Pregnancy cat.	C(AU) C(US)
Legal status	P(UK) ℞-only(US) (injection POM(UK))
Routes	Oral, rectal, IV, IM

Promethazine is a first-generation H₁ receptor antagonist antihistamine and antiemetic medication. It is a prescription drug in the United States, but is available over the counter in the United Kingdom, Switzerland, and many other countries (brand names Phenergan, Promethegan, Romergan, Fargan, Farganesse, Prothiazine, Avomine, Atosil, RhinathioL).

Promethazine also has strong anticholinergic and sedative/hypnotic effects. Previously it was used as an antipsychotic, although it is generally not administered for this purpose now; promethazine has only approximately 1/10 of the antipsychotic strength of chlorpromazine.

Indications

• As sedative/hypnotic
• For preoperative sedation and to counteract postnarcotic nausea
• As antiallergic medication to combat hay fever, allergic rhinitis, etc. To treat allergic reactions it can be given alone or in combination with oral decongestants like pseudo-ephedrine.
• As an adjunct treatment for anaphylactoid conditions (IM/IV route preferred).
• Together with codeine or dextromethorphan against cough
• As a motion sickness or seasickness remedy when used with Ephedrine or Pseudoephedrine.
• As an antipruritic (pruritus vulvae).
• To combat 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 line being metoclopramide or prochlorperazine).British National Formulary (March 2003). "4.6 Drugs used in nausea and vertigo - Vomiting of pregnancy", "BNF", 45.  Whilst in the US, Zofran (ondansetron) is the usual drug of choice, though the high cost is prohibitive for some women.

Contraindications

• Promethazine should not be given to children under two years of age; there is potential for fatal respiratory depression in this age group.Letter from Wyeth Pharmaceuticals to practitioners regarding use of Phenergan in under twos (PDF). FDA.
• Hypersensitivity to Phenothiazines
• Closed angle glaucoma
• Intoxication with alcohol or other central depressants
• Severe hypotension or shock
• Coma due to any reason
• Severely impaired liver function
• Urine hesitancy due to enlargement of the prostate gland

Mechanism of Action

• Promethazine is a phenothiazine derivative that competitively blocks histamine H₁ receptors without blocking the secretion of histamine.(http://www.thomsonhc.com/hcs/librarian/ND_PR/Main/SBK/2/PFPUI/ynPL0K2k0lcWx/ND_PG/PRIH/CS/F634E2/ND_T/HCS/ND_P/Main/DUPLICATIONSHIELDSYNC/C82994/ND_B/HCS/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/487580/ContentSetId/100/SearchTerm/prometha%20/SearchOption/BeginWith#secN66981)
• It has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects
• However, unlike other phenothiazines, it has no dopaminergic action due to a structural difference with other phenothiazines.

Side effects

Typical side effects are:

• Blurred vision
• Confusion in the elderly
• Drowsiness, dizziness, fatigue, more rarely vertigo
• Dry mouth
• Seizures (extremely rare)
• Neuroleptic malignant syndrome (extremely rare)
• Respiratory depression in patients under age of 2 and in those with severely compromised pulmonal function
• Constipation
• Euphoria (very rare with high IV doses and/or coadministration with opioids/CNS depressants)
• Restless legs [1][2]

Laboratory examinations

All patients should have their blood pressure measured frequently. During long-term therapy, blood cell counts, liver function studies, EKG, and EEG are recommended. The intervals should be determined according to the risk profile of the patient. In high doses Promethazine can create auditory and visual hallucinations causing panic and intense fear. If mixed with alcohol less needs to be taken to get these effects therefore can really take someone by surprise.^{[citation needed]}

Recreational use

Promethazine is sometimes used as a recreational drug in conjunction with codeine in prescription cough syrup. The syrup by itself contains 7% alcohol. The mixture of Sprite and cough syrup with codeine, which is known as "purple drank" or "Sizzurp", is popularized in the rap world, especially in the Houston area.Peters RJ, Kelder SH, Markham CM, Yacoubian GS, Peters LA, Ellis A (2003). "Beliefs and social norms about codeine and promethazine hydrochloride cough syrup (CPHCS) onset and perceived addiction among urban Houstonian adolescents: an addiction trend in the city of lean". J Drug Educ 33 (4): 415–25. doi:10.2190/NXJ6-U60J-XTY0-09MP. PMID 15237866.  It is also sometimes used to counteract nausea caused by illicit opioid use.

Promethazine is referred to as "zazz" on Baltimore streets, as in "let\'s get zazzed". This combination of drugs played a role in the death of rapper Pimp C, who had sung with Three 6 Mafia and Underground Kingz about mixing promethazine and codeine in the hit song "Sippin\' On Some Sizzurp." Pimp C stopped breathing from an overdose of the mixture on December 4, 2007, he also suffered from sleep apnea which played a major role in his death. The combination of his breathing disorder and the shallow breathing the syrup causes proved to be a lethal combination. DJ Screw and Big Moe, also of Southern Texas fame, also died with high levels of promethazine/codeine/alcohol in their blood stream.http://news.yahoo.com/s/ap/20080205/ap_en_ce/people_pimp_c;_ylt=Ap2w.oDtWTdoNPpzY1FErQ6s0NUE

References

• (2004) Basic and Clinical Pharmacology, 9th ed, Katzung, Bertram G., pp. 264–265. 

Footnotes

External links

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

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