Phentermine

Phentermine is used for a short period of time to promote weight loss, if exercise and calorie reduction are not sufficient, and in addition to exercise and calorie reduction. ==Contraindications==

Use is not recommended during pregnancy or breastfeeding, or with selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs). Phentermine is contraindicated for users who: • have a history of drug abuse • are allergic to sympathomimetic amine drugs • are taking a monoamine oxidase inhibitor (MAOI) or have taken one within the last 14 days • have cardiovascular disease, hyperthyroidism, or glaucoma • are pregnant, planning to become pregnant, or breastfeeding. ==Adverse effects==

Tolerance usually occurs; however, risks of dependence and addiction are considered negligible. People taking phentermine may be impaired when driving or operating machinery. • Cardiovascular effects like palpitations, tachycardia, high blood pressure, precordial pain; rare cases of stroke, angina, myocardial infarction, cardiac failure and cardiac arrest have been reported. • Central nervous system effects like overstimulation, restlessness, nervousness, insomnia, tremor, dizziness and headache; there are rare reports of euphoria followed by fatigue and depression, and very rarely, psychotic episodes and hallucinations. • Gastrointestinal effects include nausea, vomiting, dry mouth, cramps, unpleasant taste, diarrhea, and constipation. • Other adverse effects include trouble urinating, rash, impotence, changes in libido, and facial swelling. ==Interactions==

Phentermine may decrease the effect of drugs like clonidine, methyldopa, and guanethidine. Drugs to treat hypothyroidism may increase the effect of phentermine. ==Pharmacology==

Pharmacodynamics Monoamine releasing agent Phentermine is a substrate of the monoamine transporters (MATs) and acts as a monoamine releasing agent (MRA), specifically as a norepinephrine–dopamine releasing agent (NDRA). It also acts as a norepinephrine–dopamine reuptake inhibitor (NDRI) to a lesser extent. Due to its actions on the catecholamines, phentermine produces effects including stimulation, rewarding effects, appetite suppression, and sympathomimetic effects in animals and humans. Although phentermine induces the release of dopamine at sufficiently high concentrations in vitro and at sufficiently high doses in rodents and monkeys in vivo, it may result in only weak or negligible brain dopamine release in humans at typical clinical doses. Conversely, combined phentermine and fenfluramine administration synergistically enhances the appetite suppression of these drugs in animals and results in greater weight loss than either drug alone in humans. It appears to be a weak human TAAR1 partial agonist ( = 5,470nM and = 68% in one study). Phentermine is a very weak monoamine oxidase inhibitor (MAOI) in vitro. It specifically inhibits monoamine oxidase A (MAO-A) ( = 85,000–143,000nM) and monoamine oxidase B (MAO-B) ( = 285,000nM). Peak concentrations of phentermine are reached 6hours following oral administration of a dose of 15mg. Its weakly basic nature facilitates absorption in the small intestine, where it exists primarily in a non-ionized form at physiological pH. Peak plasma concentrations can vary slightly based on formulation (immediate vs. extended-release) and gastric motility. suggesting a low potential for clinically meaningful drug–drug interactions. Variations in metabolic rate due to hepatic function generally have less effect on overall clearance compared to renal factors. Elimination The drug is eliminated mainly in urine. It is excreted 62 to 85% unchanged in urine. The elimination half-life of phentermine is 20 to 25hours. The elimination of phentermine is modified by urine acidicity or pH. In the case of acidic urine (pH < 5), the elimination half-life of phentermine has been found to be 7 to 8hours. The clearance of phentermine is 8.79L/h. ==History==

In 1959, phentermine first received approval from the US Food and Drug Administration (FDA) as an appetite suppressant. Eventually a hydrochloride salt and a resin form became available. 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 showed nearly 30% of people taking fenfluramine or dexfenfluramine for up to 24 months had abnormal valve findings. Phentermine is still available by itself in most countries, including the US. In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act. In contrast, amphetamine preparations are classified as Schedule II controlled substances. A company called Vivus developed a combination drug, phentermine/topiramate that it originally called Qnexa and then called Qsymia, which was invented and used off-label by Thomas Najarian, who opened a weight-clinic in Los Osos, California in 2001; Najarian had previously worked at Interneuron Pharmaceuticals, which had developed one of the fen-phen drugs previously withdrawn from the market. The FDA rejected the combination drug in 2010 due to concerns over its safety. At the time, one obesity specialist estimated that around 70% of his colleagues were already prescribing the combination off-label. ==Chemistry==

Phentermine, also known as α,α-dimethylphenethylamine or as α-methylamphetamine, is a substituted phenethylamine and amphetamine. It is the derivative of amphetamine in which a second methyl group is present at the alpha carbon. The drug is a positional isomer of methamphetamine (N-methylamphetamine) and of other methylamphetamines such as 4-methylamphetamine. Derivatives A number of derivatives of phentermine exist, including cericlamine, chlorphentermine, cloforex, clortermine, etolorex, mephentermine, 3,4-methylenedioxyphentermine (MDPH), 3,4-methylenedioxy-N-methylphentermine (MDMP or MDMPH), and pentorex, among others. Some of these drugs, including chlorphentermine, cloforex, clortermine, and mephentermine, have been marketed as pharmaceutical drugs similarly to phentermine, for instance as appetite suppressants. ==Society and culture==

Etymology The term phentermine is contracted from phenyl-tertiary-butyl amine. Brand names Phentermine is marketed under many brand names and formulations worldwide, including Acxion, Adipex, Adipex-P, Duromine, Elvenir, Fastin, Ionamin, Lomaira (phentermine hydrochloride), Panbesy, Qsymia (phentermine and topiramate), Razin, Redusa, Sentis, Suprenza, and Terfamex. == References ==