Phentermine 1270794 226139621 2008-07-17T00:14:49Z Ohnoitsjamie 507787 Reverted edits by [[Special:Contributions/71.226.135.10|71.226.135.10]] ([[User talk:71.226.135.10|talk]]) to last version by Ahoerstemeier {{drugbox | IUPAC_name = 2-methyl-1-phenylpropan-2-amine and 2-methyl-amphetamine | image = Phentermine.png | image2 = Phentermine-3d-CPK.png | width = 200 | CAS_number = 122-09-8 | ATC_prefix = A08 | ATC_suffix = AA01 | ATC_supplemental = {{ATC|C01|CA11}} | PubChem = 4771 | DrugBank = APRD00093 | C=10 | H=15 | N=1 | molecular_weight = 149.233 g/mol | bioavailability = Peak plasma levels occur within 1 to 4.5 hours. Absorption is usually complete by 4 to 6 hours | protein_bound = Approximately 96.3% | metabolism = hepatic | elimination_half-life = 16 to 31 hours | pregnancy_AU = | pregnancy_US = C | pregnancy_category = | legal_US = Schedule IV | legal_status = | routes_of_administration = Oral | excretion = Urinary elimination }} '''Phentermine''', a contraction for "[[phenyl|'''phen'''yl]]-[[Butyl#Nomenclature|'''ter'''tiary-butyl]][[amine|a'''mine''']]", is an [[appetite suppressant]] of the [[amphetamine]] and [[phenethylamine]] class. It is approved as an appetite suppressant to help reduce weight in obese patients when used short-term and combined with exercise, diet, and behavioral modification. It is typically prescribed for individuals who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite. ==Commercial trade names== *'''Adipex P''' (Immediate release) *'''Anoxine-AM''' *'''Fastin''' (discontinued) *'''Ionamin''' (Slow Release Resin, Australia, discontinued in the US) *'''Duromine''' (Slow Release Resin, New Zealand & Australia) *'''Obephen''' *'''Obermine''' *'''Obestin-30''' *'''Phentrol''' *'''Phenterex''' *'''Phentromine''' *'''Pro-Fast SA''' *'''Redusa''' *'''Panbesy''' *'''Phentermine Trenker''' *'''Obenix''' *'''Oby-Trim''' *'''Teramine''' *'''Zantryl''' *'''Sinpet '''(MX) *'''Supremin''' (PH) *'''Umine''' (NZ) *'''Weltmine''' (KP) ==History== In 1959 phentermine first received approval from the FDA as an appetite suppressing drug. Phentermine hydrochloride then became available in the early 1970s. It was previously sold as Fastin from King Pharmaceuticals for [[SmithKline Beecham]], however in 1998 it was removed from the market. [[Medeva Pharmaceuticals]] sells the name brand of phentermine called [[Ionamin]] and [[Gate Pharmaceuticals]] sells it as [[Adipex-P]]. Phentermine is also currently sold as a generic. Since the drug was approved in 1959 there have been almost no clinical studies performed. The most recent study was in 1990 which combined phentermine with [[fenfluramine]] or [[dexfenfluramine]] and became known as [[Fen-Phen]].{{Fact|date=May 2008}} A study was published in 1992 that Fen-Phen was more effective than diet and exercise with few side effects.{{Fact|date=May 2008}} However, in 1997 after 24 cases of heart valve disease in Fen-Phen users, fenfluramine and dexfenfluramine were voluntarily taken off the market at the request of the FDA. Studies later proved that nearly 30% of people taking fenfluramine or dexfenfluramine had abnormal valve findings. The FDA did not ask manufacturers to remove phentermine from the market. {{Fact|date=May 2008}} Phentermine is still available by itself in most countries, including the U.S. However, because it is similar to [[amphetamines]], individuals may develop an [[Drug addiction|addiction]] to it. Hence, it is classified as a [[controlled substance]] in many countries. Internationally, phentermine is a schedule IV drug under the [[Convention on Psychotropic Substances]].<ref>[http://www.incb.org/pdf/e/list/green.pdf Incb.org (PDF file)]</ref> In the United States, it is classified as a [[Schedule IV]] controlled substance under the [[Controlled Substances Act]]. ==Mechanism of action== [[Image:Phentermine.jpg|frame|left]] Phentermine, like many other prescription drugs, works with [[neurotransmitter]]s in the brain. It is a centrally-acting [[stimulant]] and is a [[structural isomer|constitutional isomer]] (not to be confused with [[stereoisomer]]) of [[methamphetamine]]. It stimulates [[neuron]] bundles to release a particular group of neurotransmitters known as [[catecholamine]]s; these include [[dopamine]], [[epinephrine]] (also known as adrenaline), and [[norepinephrine]] (noradrenaline). The anorectic activity seen with these compounds is thus likely due to their effect on the [[central nervous system]], which is consistent with current knowledge about the central nervous system and feeding behavior. This is the same [[mechanism of action]] as other stimulant appetite suppressants such as [[diethylpropion]] and [[phendimetrazine]]. The neurotransmitters signal a [[fight-or-flight response]] in the body which, in turn, puts a halt to the hunger signal. As a result, it causes a loss in appetite because the brain does not receive the hunger message.{{Fact|date=May 2008}} ==Dosing and administration== Generally, it is recommended by the [[Food and Drug Administration]] (FDA) that phentermine should be used short-term (usually interpreted as 'up to 12 weeks'), while following nonpharmacological approaches to weight loss such as healthy [[dieting]] and [[exercise]].{{Fact|date=May 2008}} However, recommendations limiting its use for short-term treatment may be controversial. One reason given behind limiting its use to 12 weeks is [[drug tolerance]], whereby phentermine loses its appetite-suppressing effects after the body adjusts to the drug. On the contrary, it has been shown that phentermine did not lose effectiveness in a 36-week trial.<ref>PMID 11054601</ref> Developing tolerance can usually be avoided long-term by taking phentermine 5 consecutive days, then skipping 2 days each week.{{Fact|date=May 2008}} Due to the risk of [[insomnia]], it is generally recommended that the drug be taken either before breakfast or 1-2 hours after breakfast.{{Fact|date=May 2008}} ==Contraindications and warnings== *Patients with the following '''should not use''' Phentermine: **An [[allergy]] to any ingredient in Phentermine or other [[sympathomimetic]]s (eg, [[pseudoephedrine]]) **Are also taking [[dexfenfluramine]], [[fenfluramine]], [[furazolidone]], [[guanadrel]], [[guanethidine]], or have taken a [[monoamine oxidase inhibitor]] (MAOI) (eg, phenelzine) in the last 14 days **Have severe [[high blood pressure]], an [[overactive thyroid]], [[glaucoma]], heart or blood vessel disease, or severe narrowing of the blood vessels **Are in an agitated state, or have a history of [[substance abuse]] *Some '''medical conditions may interact''' with Phentermine, patients with the following should consult with their doctor before using phentermine: **Are [[pregnant]], planning to become pregnant, or are [[breast-feeding]] **Are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement **Have [[allergies]] to medicines, foods, or other substances **Have a brain or spinal cord disorder, hardening of the arteries, [[high blood pressure]], [[diabetes]], or [[high cholesterol]] or lipid levels *Some '''medicines may interact''' with phentermine, such as the following: **Dexfenfluramine, fenfluramine, furazolidone, or MAOIs (eg, phenelzine) because the risk of serious side effects, such as increasing headache, high blood pressure, slow heart rate, elevated temperature, or possibly fatal lung problems, may be increased **Serotonin specific reuptake inhibitors (citalopram ([[Celexa]]), escitalopram ([[Lexapro]]), fluoxetine ([[Prozac]], [[Sarafem]]), fluvoxamine ([[Luvox]]), paroxetine ([[Paxil]]), or sertraline ([[Zoloft]])) because the risk of their side effects may be increased by Phentermine **Guanadrel(Hylorel) or guanethidine(Ismelin) because their effectiveness may be decreased by phentermine **Antacids: Antacids may decrease the excretion of phentermine. <ref name=merck.com>{{cite web | Drug Information Provided by Lexi-Comp | title =Phentermine | publisher=Merck & Co., Inc. | url=http://www.merck.com/mmpe/lexicomp/phentermine.html | year = 2008 | accessdate=2008-05-15}}</ref> **Carbonic anhydrase inhibitors (acetazolamide, dichlorphenamide, methazolamide): Carbonic anhydrase inhibitors may decrease the excretion of phentermine.<ref name="merck.com" /> ==Side effects== Generally, phentermine appears to be relatively well tolerated.<ref name=Nelson>{{cite web | author = Nelson DL, Gehlert DR. | year = 2006 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16622292&query_hl=49&itool=pubmed_docsum | title = Central nervous system biogenic amine targets for control of appetite and energy expenditure. | format = HTML | work = Endocrine. 2006 Feb;29(1):49-60 | publisher = PubMed | accessdate = 6 May | accessyear = 2006}}</ref> It can produce side effects consistent with its catecholamine-releasing properties, e.g., tachycardia (increased heart rate) and elevated blood pressure, but the incidence and magnitude of these appear to be less than with the amphetamines. Because phentermine acts through [[sympathomimetic]] pathways, the drug may increase [[blood pressure]] and [[heart rate]]. It may also cause [[palpitation]]s, restlessness, and [[insomnia]]. Additionally, phentermine has the potential to cause physical and psychological dependence. ===More common symptoms=== * Insomnia * Increased blood pressure * Irritability * Nervousness * Sense of well-being * Dry mouth * Unpleasant taste * Insomnia * Blurred vision * Heartburn/Acid reflux * Change in sexual desire * Clumsiness * Confusion * Diarrhea * Dizziness * Headache * Irregular heartbeat * Nausea or vomiting * Psychosis * Skin rash or itching * Stomach pain * Tiredness ===Less common symptoms=== *Confusion *Convulsions (seizures) *Dizziness *Fast breathing *Fever *Hallucinations *Hostility with urge to attack *Irregular blood pressure *Irregular heartbeat *Lightheadedness or fainting *Mental depression, following a period of excitement *Tremors, trembling or shaking *Overactive reflexes *Panic *Restlessness *Severe nausea, vomiting or diarrhea *Stomach cramps *Tiredness or weakness ==References== {{reflist}} ==External links== *[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682187.html MedLine Plus - Phentermine] *[http://www.inchem.org/documents/pims/pharm/pim415.htm International Programme on Chemical Safety - Phentermine] *[http://toxnet.nlm.nih.gov/ TOXNET] *[http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00093.txt DrugBank:Phentermine] {{Phenethylamines}} {{stimulants}} {{Antiobesity preparations}} [[Category:Anorectics]] [[Category:Phenethylamines]] [[Category:Stimulants]] [[de:Phentermin]] [[fr:Phentermine]] [[pl:Fentermina]] [[ru:Фентермин]] [[fi:Fentermiini]]