Promethazine
![Promethazine.svg](/2009-wikipedia_en_wp1-0.7_2009-05/I/125px_Promethazine_svg.png) |
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
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
- ↑ RxList: Promethazine
- ↑ [1]
- ↑ http://www.rxlist.com/cgi/generic/phenergan.htm RxList: Promethazine Description
- ↑ 4.0 4.1 4.2 4.3 4.4 RxList Indications for Promethazine
- ↑ British National Formulary (March 2003). "4.6 Drugs used in nausea and Vertigo - Vomiting of pregnancy". "BNF" (45 ed.).
- ↑ "Letter from Wyeth Pharmaceuticals to practitioners regarding use of Phenergan in under twos" (PDF). FDA.
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 RxList Contraindications
- ↑ David J McCann and Brett Roth, Toxicity, Antihistamine, eMedicine Toxicology, updated June 21, 2007
- ↑ Cordingley Neurology
- ↑ Baxter: Promethazine HCl Injection, USP Information
- ↑ 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.
- ↑ Liptak, Adam (2008-09-18). "Drug Label, Maimed Patient and Crucial Test for Justices", The New York Times. Retrieved on 2008-10-31.
External links
- "Promethazine". U.S. National Library of Medicine and National Institutes of Health.
Antipruritics (D04) |
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Antihistamines for topical use |
Thonzylamine - Mepyramine - Thenalidine - Tripelennamine - Chloropyramine - Promethazine - Tolpropamine - Dimetindene - Clemastine - Bamipine - Isothipendyl - Diphenhydramine - Chlorphenoxamine
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Anesthetics for topical use |
Lidocaine - Cinchocaine - Oxybuprocaine - Benzocaine - Quinisocaine - Tetracaine - Pramocaine
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Histamine antagonists |
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H1 |
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Alkylamines
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Bepotastine • Bamipine • Brompheniramine • Chlorpheniramine • Dexbrompheniramine • Dexchlorpheniramine • Dimethindene • Iproheptine • Pheniramine • Pyrrobutamine • Talastine • Thenalidine • Tolpropamine • Triprolidine
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Ethanolamines
(Aminoalkyl ethers)
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Bromazine/Bromodiphenhydramine • Carbinoxamine • Chlorphenoxamine • Clemastine • Diphenylpyraline • Diphenhydramine • Doxylamine • Embramine • p-Methyldiphenhydramine • Moxastine • Orphenadrine • Phenyltoloxamine • Setastine
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Ethylenediamines
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Chloropyramine • Chlorothen • Histapyrrodine • Methafurylene • Mepyramine • Methapyrilene • Pyrilamine • Talastine • Thenyldiamine • Thonzylamine • Tripelennamine (Pyribenzamine)
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Phenothiazine Tricyclics
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Ahistan • Etymemazine • Hydroxyethylpromethazine • Isopromethazine • Isothipendyl • Mequitazine • Methdilazine • Oxomemazine • Promethazine • Thiazinamium
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Other Tricyclics
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Azatadine • Clobenzepam • Cyproheptadine • Deptropine • Isothipendyl
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Piperazine
|
Buclizine • Chlorcyclizine • Cinnarizine • Clocinizine • Hydroxyzine • Niaprazine • Oxatomide • Benzhydryl compounds (Cyclizine, Meclizine)
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Acrivastine
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Olopatadine
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Piperazine
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Cetirizine
|
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Benzhydryl
|
Terfenadine
|
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Other/
ungrouped
|
Antazoline • Astemizole • Azatadine • Azelastine • Bamipine • Clemizole • Clobenztropine • Deptropine • Dimebon • Ebastine • Emedastine • Epinastine • Ketotifen • Levocabastine • Loratadine • Mebhydrolin • Mizolastine • Phenindamine • Pimethixene • Pyrrobutamine • Rupatadine • Thenalidine • Tritoqualine
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Levocetirizine • Desloratadine • Fexofenadine
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H2 |
Cimetidine • Famotidine • Ranitidine • Roxatidine • Lafutidine • Niperotidine • Nizatidine
|
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H3 |
A-349,821 • A-423,579 • ABT-239 • BF-2649 • Burimamide • Ciproxifan • Clobenpropit • Conessine • GSK-189,254 • Impentamine • Iodophenpropit • JNJ 5207852 • MK-0249 • NNC 38-1049 • SCH-79687 • Thioperamide • VUF-5681
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H4 |
JNJ 7777120 • Thioperamide • VUF-6002
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