1 : 1 mixture (racemate)

Systematic (IUPAC) name
(RS)-N,N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine
Identifiers
CAS number	60-87-7 58-33-3 (hydrochloride)
ATC code	D04AA10 R06AD02, R06AD05
PubChem	4927
DrugBank	APRD00601
ChemSpider	4758
Chemical data
Formula	C17H20N2S
Mol. mass	284.42 g/mol
SMILES	eMolecules & PubChem
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, topical
Y(what is this?)  (verify)

Promethazine is a first-generation H₁ receptor antagonist used medically as an antihistamine and antiemetic. It can also have strong sedative effects and in some countries is prescribed for insomnia when benzodiazepines are contraindicated. It is a prescription drug in the United States but is available over the counter in the United Kingdom, Australia, Canada, Switzerland, and many other countries (brand names Phenergan, Promethegan, Romergan, Fargan, Farganesse, Prothiazine, Avomine, Atosil, Receptozine, Lergigan).^[1]

Chemically, promethazine hydrochloride appears as a white to faint yellow crystaline powder that is practically odorless. Slow oxidation may occur upon prolonged exposure to air usually causing blue discoloration. Promethazine as the hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers (pictured).^[2]

[edit] Indications

• As a sedative.^[3]
• For preoperative sedation and to counteract postnarcotic nausea.^[3]
• 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 pseudoephedrine.^[3]
• As an adjunct treatment for anaphylactoid conditions (IM/IV route preferred).^[3]
• Together with codeine or dextromethorphan against cough.
• As a motion sickness or seasickness remedy when used with Ephedrine or Pseudoephedrine.^[3]
• 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).^[4]
• Previously it was used as an antipsychotic^[5]., although it is generally not administered for this purpose now; promethazine has only approximately 1/10 of the antipsychotic strength of chlorpromazine.
• Also used to potentiate any opiates. Commonly combined with pethidine (AKA, meperidine, or Demerol) in a brand called Mepergan, a meperidine/promethazine combination. Also frequently used in conjunction with codeine, in a syrup form. The combination leads to a more powerful opiate than codeine alone.

[edit] Mechanism of action

• Promethazine is a phenothiazine derivative that competitively blocks histamine H₁ receptors without blocking the secretion of histamine. It also is a very weak dopamine antagonist .^[6]
• It has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects

[edit] Side effects

Some common side effects include:

• Confusion in the elderly
• Drowsiness, dizziness, fatigue, more rarely vertigo
• Dry mouth
• 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 ^[7]
• Paresthesia

Extremely rare side effects include:

• Seizures (extremely rare)
• Neuroleptic malignant syndrome (extremely rare)

It is recommended that promethazine only be given through an existing intravenous set in a large vein and diluted to concentration no greater than 25mg per mL, not to exceed a rate of administration of 25mg a min. Serious complications including those listed above have resulted from improper parenteral administration, including those requiring surgical intervention and amputation.^[8]

Because of potential for more severe side effects, this drug is on the list to avoid in the elderly. (See NCQA’s HEDIS Measure: Use of High Risk Medications in the Elderly).

[edit] 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.

[edit] Case law

The U.S. Supreme Court accepted a case involving promethazine that influences product liability. Diana Levine, a woman suffering from 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 pre-emption and substantive due process.^[9] 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.^[10] In effect, this means that drug manufacturers can be held liable for injuries if the FDA-approved warnings of potential adverse affects is deemed insufficient by state courts.

[edit] See Also

• Initiating the Jonestown Massacre, and metal vat with Flavor Aid, poisoned with Valium, chloral hydrate, cyanide and Phenergan, which was then consumed orally.

[edit] References

[edit] External links

• "Promethazine". U.S. National Library of Medicine and National Institutes of Health. http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682284.html.