WordNet
- antihistamine (trade name Phenergan) used to treat allergies; also an antiemetic used to treat motion sickness (同)Phenergan
- a complex consisting of an organic base in association with hydrogen chloride
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/02 13:15:16」(JST)
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| 1:1 mixture (racemate) | |
| Systematic (IUPAC) name | |
| (RS)-N,N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine | |
| Clinical data | |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a682284 |
| Pregnancy cat. | C (AU) C (US) |
| Legal status | ℞-only (US) (injection POM(UK)) |
| Routes | 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 |
| Half-life | 16-19 hours[1][2] |
| Excretion | Renal and biliary |
| Identifiers | |
| CAS number | 60-87-7 Y 58-33-3 (hydrochloride) |
| ATC code | D04AA10 R06AD02, R06AD05 |
| PubChem | CID 4927 |
| DrugBank | DB01069 |
| ChemSpider | 4758 Y |
| UNII | FF28EJQ494 Y |
| KEGG | D00494 Y |
| ChEBI | CHEBI:8461 Y |
| ChEMBL | CHEMBL643 Y |
| Chemical data | |
| Formula | C17H20N2S |
| Mol. mass | 284.42 g/mol |
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Promethazine is a neuroleptic medication and first-generation antihistamine of the phenothiazine family. The drug has strong sedative and weak antipsychotic effects. At the same time it causes motion sickness reduction and has antiemetic, and anticholinergic properties. In some countries it is prescribed for insomnia when benzodiazepines are contraindicated. It is available in many countries under the brand names Phenergan, Promethegan, Romergan, Fargan, Farganesse, Prothiazine, Avomine, Atosil, Receptozine, Lergigan, and Sominex.[3]
Contents
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Indications
- As a sedative[4]
- For preoperative sedation and to counteract postnarcotic nausea[4]
- To reduce nervousness, restlesness and agitation caused by psychiatric conditions (used for this purpose mainly in Europe)
- As antiallergic medication to combat hay fever (allergic rhinitis), etc., or to treat allergic reactions, alone or in combination with oral decongestants such as 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 in line being metoclopramide or prochlorperazine).[5]
- Previously, it was used as an antipsychotic,[6] although it is generally not administered for this purpose now; promethazine has only approximately 1/10 of the antipsychotic strength of chlorpromazine.
- Also, it is used to potentiate any opiates, commonly combined with pethidine (meperidine, or Demerol) in a brand called Mepergan, a meperidine/promethazine combination. It is frequently used in conjunction with codeine, in a syrup form. The combination leads to more powerful euphoric effects than with codeine alone.
- Treatment for migraines
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).[7]
Promethazine, 10-(2-dimethylaminopropyl)phenothiazine, is synthesized by alkylating phenothiazine with 1-chloro-2-(dimethylamino)propane in the presence of sodium amide:[8][9][10]
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,[11] 5-HT2C,[11] D2,[12][13] and α1-adrenergic receptors,[14] 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.[14]
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)
- Euphoria (very rare, except with high IV doses and/or coadministration with opioids/CNS depressants)
- Akathisia [15]
- Paresthesia
- Short temper/irritability
Extremely rare side effects include:
- Seizures
- Neuroleptic malignant syndrome
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. [16]
Product liability lawsuit
Main article: Wyeth v. Levine
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.[17] 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.[18] 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 promethazine, stating the contraindication for subcutaneous administration. The preferred administrative route is intramuscular, which reduces risk of surrounding muscle and tissue damage.[19]
See also
- Purple drank (a recreational drug concoction containing promethazine)
References
- ^ a b c d Strenkoski-Nix LC, Ermer J, DeCleene S, Cevallos W, Mayer PR (August 2000). "Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects". American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists 57 (16): 1499–505. PMID 10965395.
- ^ Paton DM, Webster DR (1985). "Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines)". Clinical Pharmacokinetics 10 (6): 477–97. PMID 2866055.
- ^ RxList: Promethazine
- ^ a b c d e RxList Indications for Promethazine
- ^ British National Formulary (March 2001). "4.6 Drugs used in nausea and Vertigo - Vomiting of pregnancy". BNF (45 ed.). .
- ^ [1].
- ^ http://www.rxlist.com/cgi/generic/phenergan.htm RxList: Promethazine Description
- ^ Beringer, Paul; Troy, David A.; Remington, Joseph P. (2006). Remington: The Science and Practice of Pharmacy. Hagerstown, MD: Lippincott Williams & Wilkins. p. 1545. ISBN 0-7817-4673-6.
- ^ P. Charpentier, U.S. Patent 2,530,451 (1950)
- ^ S.B. Sidney, J.A. Nicholson, U.S. Patent 2,607,773 (1952)
- ^ a b Fiorella D, Rabin RA, Winter JC (October 1995). "The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis". Psychopharmacology 121 (3): 347–56. PMID 8584617.
- ^ Seeman P, Watanabe M, Grigoriadis D, et al. (November 1985). "Dopamine D2 receptor binding sites for agonists. A tetrahedral model". Molecular Pharmacology 28 (5): 391–9. PMID 2932631.
- ^ Burt DR, Creese I, Snyder SH (April 1977). "Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain". Science 196 (4287): 326–8. doi:10.1126/science.847477. PMID 847477.
- ^ a b Jagadish Prasad, P. (2010). Conceptual Pharmacology. Universities Press. pp. 295, 303, 598. ISBN 978-81-7371-679-9. Retrieved 27 November 2011.
- ^ Cordingley Neurology
- ^ Starke P, Weaver J, Chowdhury B. Boxed warning added to promethazine labeling for pediatric use. N Eng J Med. 2005;352(5):2653.
- ^ Liptak, Adam (2001-09-18). "Drug Label, Maimed Patient and Crucial Test for Justices". The New York Times. Retrieved 2008-10-31.
- ^ Stout, David (2009-03-04). "Drug Approval Is Not a Shield From Lawsuits, Justices Rule". The New York Times. Retrieved 2009-03-04.
- ^ http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm182169.htm
External links
- "Promethazine". U.S. National Library of Medicine and National Institutes of Health.
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UpToDate Contents
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- 1. 妊娠の悪心および嘔吐の治療および転帰 treatment and outcome of nausea and vomiting of pregnancy
- 2. 小児におけるウイルス性胃腸炎の予防および治療 prevention and treatment of viral gastroenteritis in children
- 3. 緩和ケアにおける呼吸困難の評価と管理 assessment and management of dyspnea in palliative care
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English Journal
- Multiple Time-of-Flight/Time-of-Flight Events in a Single Laser Shot for Improved Matrix-Assisted Laser Desorption/Ionization Tandem Mass Spectrometry Quantification.
- Prentice BM1, Chumbley CW1, Hachey BC1, Norris JL1, Caprioli RM1.
- Analytical chemistry.Anal Chem.2016 Sep 14. [Epub ahead of print]
- Quantitative matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) approaches have historically suffered from poor accuracy and precision mainly due to the nonuniform distribution of matrix and analyte across the target surface, matrix interferences, and ionization suppression. Tand
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- Potential drug-drug interactions in paediatric outpatient prescriptions in Nigeria and implications for the future.
- Oshikoya KA1, Oreagba IA2, Godman B3,4, Oguntayo FS2, Fadare J5, Orubu S6, Massele A7, Senbanjo IO8.
- Expert review of clinical pharmacology.Expert Rev Clin Pharmacol.2016 Sep 3. [Epub ahead of print]
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- Studies on the interaction between promethazine and human serum albumin in the presence of flavonoids by spectroscopic and molecular modeling techniques.
- He LL1, Wang ZX1, Wang YX1, Liu XP1, Yang YJ1, Gao YP1, Wang X2, Liu B3, Wang X4.
- Colloids and surfaces. B, Biointerfaces.Colloids Surf B Biointerfaces.2016 Sep 1;145:820-9. doi: 10.1016/j.colsurfb.2016.06.001. Epub 2016 Jun 2.
- Fluorescence, absorption, time-correlated single photon counting (TCSPC), and circular dichroism (CD) spectroscopic techniques as well as molecular modeling methods were used to study the binding characterization of promethazine (PMT) to human serum albumin (HSA) and the influence of flavonoids, rut
- PMID 27315330
Japanese Journal
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Related Pictures
★リンクテーブル★
| リンク元 | 「プロメタジン」「promethazine methylenedisalicylate」「promethazine teoclate」「塩酸プロメタジン」 |
| 関連記事 | 「hydrochloride」 |
「プロメタジン」
- 英
- promethazine
- ラ
- promethazinum
- 化
- 塩酸プロメタジン promethazine hydrochloride
- 商
- Phenergan。PL配合、サラザック、セラピナ配合、トーワチーム配合、ピーエイ配合、ヒベルナ、ピレチア、プロモーション、ベゲタミン-A配合、マリキナ配合
- 関
- 抗ヒスタミン薬
- 古典的抗ヒスタミン薬
- フェノチアジン系。ヒスタミンH1受容体拮抗薬
- 抗ヒスタミン作用はジフェンヒドラミンの約30倍。
- 抗アナフィラキシー作用
- 中枢性抗コリン作用はトリヘキシフェニジルの約2.8倍。