Promethazine

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Promethazine
Promethazine.svg
Promethazine ball-and-stick model.png
1:1 mixture (racemate)
Systematic (IUPAC) name
(RS)-N,N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine
Clinical data
Trade names Phenergan
AHFS/Drugs.com monograph
MedlinePlus a682284
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Legal status
Routes of
administration
Oral, rectal, IV, IM, topical
Pharmacokinetic data
Bioavailability 88% absorbed but after first-pass metabolism reduced to 25% absolute bioavailability[1]
Protein binding 93%
Metabolism Hepatic glucuronidation and sulfoxidation
Biological half-life 16-19 hours[1][2]
Excretion Renal and biliary
Identifiers
CAS Number 60-87-7 YesY
Template:CAS (hydrochloride)
ATC code D04AA10 (WHO) R06AD02
PubChem CID: 4927
IUPHAR/BPS 7282
DrugBank DB01069 YesY
ChemSpider 4758 YesY
UNII FF28EJQ494 YesY
KEGG D00494 YesY
ChEBI CHEBI:8461 YesY
ChEMBL CHEMBL643 YesY
Chemical data
Formula C17H20N2S
Molecular mass 284.42 g/mol
  • S2c1ccccc1N(c3c2cccc3)CC(N(C)C)C
  • InChI=1S/C17H20N2S/c1-13(18(2)3)12-19-14-8-4-6-10-16(14)20-17-11-7-5-9-15(17)19/h4-11,13H,12H2,1-3H3 YesY
  • Key:PWWVAXIEGOYWEE-UHFFFAOYSA-N YesY
  (verify)

Promethazine is a neuroleptic medication and first-generation antihistamine of the phenothiazine family. The drug has strong sedative and weak antipsychotic effects. It also reduces motion sickness and has antiemetic and anticholinergic properties (via its action on the Dopamine receptor D2). In some countries it is prescribed for insomnia when benzodiazepines are contraindicated. It is available in many countries under many brand names.[3]

Indications

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 (pictured).[8]

Pharmacology

Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects.[1] It acts primarily as a strong antagonist of the H1 receptor (antihistamine) and a moderate mACh receptor antagonist (anticholinergic),[1] and also has weak to moderate affinity for the 5-HT2A,[9] 5-HT2C,[9] D2,[10][11] and α1-adrenergic receptors,[12] where it acts as an antagonist at all sites, as well.

Another notable use of promethazine is as a local anesthetic, by blockade of sodium channels.[12]

Side effects

Some common side effects include:

  • Tardive dyskinesia
  • Confusion in the elderly
  • Drowsiness, dizziness, fatigue, more rarely vertigo
  • Dry mouth
  • Respiratory depression in patients under age of two and in those with severely compromised pulmonary function
  • Constipation
  • Chest discomfort/pressure (typically in cases when patient is already taking medication for high blood pressure)
  • Akathisia [13]
  • Paresthesia
  • Short temper/irritability

Extremely rare side effects include:

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). 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 apnoea.[14]

Society and culture

It is available in many countries under many brand names.[3]

Product liability lawsuit

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In 2009, the US Supreme Court ruled on a product liability case involving promethazine. 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 preemption and substantive due process.[15] 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.[16] 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.

On September 9, 2009, the FDA required a black box warning for injection be put on Promethean, stating the contraindication for subcutaneous administration. The preferred administrative route is intramuscular, which reduces risk of surrounding muscle and tissue damage.[17]

See also

  • Purple drank (a recreational drug concoction containing promethazine)

References

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  3. 3.0 3.1 RxList: Promethazine
  4. 4.0 4.1 4.2 4.3 4.4 RxList Indications for Promethazine
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  6. http://www.cja-jca.org/cgi/reprint/6/4/375.pdf[dead link]
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  13. Cordingley Neurology
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External links

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