Promethazine
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Promethazine
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| Systematic (IUPAC) name | |
| (RS)-N,N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine | |
| Identifiers | |
| CAS number | 58-33-3 (hydrochloride) |
| ATC code | D04 R06, R06 |
| PubChem | |
| DrugBank | |
| ChemSpider | |
| Chemical data | |
| Formula | C17H20N2S |
| Mol. mass | 284.42 g/mol |
| SMILES | & |
| 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. | |
| Legal status | |
| Routes | Oral, rectal, IV, IM, topical |
Promethazine is a first-generation H1 receptor antagonist, antihistamine and antiemetic medication. 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, Canada, Switzerland, Australia, and many other countries (brand names Phenergan, Promethegan, Romergan, Fargan, Farganesse, Prothiazine, Avomine, Atosil, Receptozine, Lergigan).[1]
Chemically, promethazine hydrochloride (HCl) 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]
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[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.
[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 (blocker).[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
- 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 [7]
- Paresthesia
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]
[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 arm 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 meant that drug manufacturers could be held liable for injuries, even if they had already warned the patients of potential adverse affects.
[edit] References
- ^ RxList: Promethazine
- ^ http://www.rxlist.com/cgi/generic/phenergan.htm RxList: Promethazine Description
- ^ a b c d e RxList Indications for Promethazine
- ^ British National Formulary (March 2003). "4.6 Drugs used in nausea and Vertigo - Vomiting of pregnancy". "BNF" (45 ed.).
- ^ [1]
- ^ David J. McCann and Brett Roth, Toxicity, Antihistamine, eMedicine Toxicology, updated June 21, 2007
- ^ Cordingley Neurology
- ^ Baxter: Promethazine HCl Injection, USP Information
- ^ Liptak, Adam (2008-09-18). "Drug Label, Maimed Patient and Crucial Test for Justices". The New York Times. http://www.nytimes.com/2008/09/19/us/19scotus.html?n=Top/Reference/Times%20Topics/Organizations/S/Supreme%20Court&_r=1&adxnnl=1&oref=slogin&adxnnlx=1225505895-T2aivHeTdvJTT7b+uEsK1Q. Retrieved on 2008-10-31.
- ^ Stout, David (2009-03-04). "Drug Approval Is Not a Shield From Lawsuits, Justices Rule". The New York Times. http://www.nytimes.com/2009/03/05/washington/05scotus.html. Retrieved on 2009-03-04.
[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.
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