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
ChemSpider	4758
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, topical

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).^[1]

Promethazine also has strong anticholinergic and sedative effects. Previously it was used as an antipsychotic^[2]., although it is generally not administered for this purpose now; promethazine has only approximately 1/10 of the antipsychotic strength of chlorpromazine.

Chemically, promethazine hydrochloride (HCl) appears as a white to faint yellow crystaline powder which is practically odorless. Slow oxidation may occur upon prolonged exposure to air causing blue discoloration. Promethazine as the hydrochloride salt is freely soluble in water and somewhat soluble in alcohol.^[3]

Indications

• As a sedative.^[4]
• For preoperative sedation and to counteract postnarcotic nausea.^[4]
• 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.^[4]
• As an adjunct treatment for anaphylactoid conditions (IM/IV route preferred).^[4]
• Together with codeine or dextromethorphan against cough.
• As a motion sickness or seasickness remedy when used with Ephedrine or Pseudoephedrine.^[4]
• 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).^[5]

Contraindications

• Promethazine should not be given to children under two years of age; there is potential for fatal respiratory depression in this age group.^[6]
• Hypersensitivity to phenothiazines^[7]
• Closed angle glaucoma^[7]
• Intoxication with alcohol or other central depressants^[7]
• Severe hypotension or shock^[7]
• Coma due to any reason^[7]
• Severely impaired liver function^[7]
• Urine hesitancy due to enlargement of the prostate gland^[7]

Mechanism of action

• Promethazine is a phenothiazine derivative that competitively blocks histamine H₁ receptors without blocking the secretion of histamine.^[8]
• It has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects

Side effects

Some common side effects include:

• 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 ^[9]
• Paresthesia
• Gangrene & Death

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.^[10]

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.

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 traditional 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.^[11] It is also sometimes used to counteract nausea caused by illicit opioid use.

Politics

The U.S. Supreme Court has accepted a case involving Promethazine that may influence product liability. A musician suffering from a migraine was administered Wyeth's Phenergan via IV push. The drug entered her arterial flow resulting in gangrene and subsequent amputation of her right arm below the elbow. A state jury awarded her $6 million in punitive damages. The case has been appealed to the Supreme Court on grounds of federal pre-emption.^[12]

References

External links

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