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Phentermine , a contraction of " phen yl- ter tiary-butyla 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.
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.
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.
Phentermine is still available by itself in most countries, including the U.S. However, because it is similar to amphetamines, it is classified as a controlled substance in many countries (including Australia). Internationally, phentermine is a schedule IV drug under the Convention on Psychotropic Substances. In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act.
Looking forward, Phentermine is being studied with another medication for obesity. The experimental appetite suppressant drug Qnexa is a mixture of Phentermine and Topiramate.
Mechanism of action
Phentermine, in doses clinically used, works on the hypothalamus portion of the brain to release norepinephrine, a neurotransmitter or chemical messenger that signals a fight-or-flight response, reducing hunger. Phentermine works outside the brain as well to release epinephrine or adrenaline causing fat cells to break down stored fat, but the principal basis of efficacy is hunger-reduction. At high doses, phentermine releases serotonin and dopamine as well, but such doses are never used in clinical medicine.
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.
Contraindications and warnings
-
Patients with the following
should not use
Phentermine:
- An allergy to any ingredient in Phentermine or other sympathomimetics (e.g., pseudoephedrine)
- Are also taking dexfenfluramine, fenfluramine, furazolidone, guanadrel, guanethidine, or have taken a monoamine oxidase inhibitor (MAOI) (e.g., 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 (e.g., 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
- Guanadrel(Hylorel) or guanethidine(Ismelin) because their effectiveness may be decreased by phentermine
- Antacids: Antacids may decrease the excretion of phentermine.
- Carbonic anhydrase inhibitors (acetazolamide, dichlorphenamide, methazolamide): Carbonic anhydrase inhibitors may decrease the excretion of phentermine.
Side effects
Generally, phentermine appears to be relatively well tolerated. 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 palpitations, restlessness, and insomnia. Additionally, phentermine has the potential to cause psychological dependence.
More common
- Insomnia
- Hypertension
- Irritability
- Nervousness
- Euphoria
- Dry mouth
- Unpleasant taste
- Blurred vision
- Heartburn/Acid reflux
- Changes in libido
- Clumsiness
- Confusion
- Diarrhea
- Dizziness
- Headache
- Arrhythmia
- Nausea or vomiting
- Psychosis
- Skin rash or itching
- Stomach pain
- Fatigue
- Pupil dilation
Less common
- Convulsions (seizures)
- Dizziness
- Fever
- Hallucinations
- Hostility with urge to attack
- Irregular blood pressure
- Lightheadedness or fainting
- Periods of mania followed by period of depression
- Tremors, trembling or shaking
- Overactive reflexes
- Panic
- Restlessness
- Severe nausea, vomiting or diarrhea
- Stomach cramps
- Weakness
Commercial trade names
- Adipex P (Immediate release)
- Adiphene (India)
- Anoxine-AM
- Ionamin (Slow Release Resin, Australia, discontinued in the US)
- Duromine (Slow Release Resin, New Zealand, Australia & South Africa)
- Metermine (Slow Release Resin, Australia)
- Mirapront
- Obephen
- Obermine
- Obestin-30
- Phentremene
- Phentrol
- Phenterex
- Phentromin
- Pro-Fast SA
- Redusa
- Panbesy
- Phentermine Trenker
- Obenix
- Oby-Trim
- Teramine
- Zantryl
- Sinpet (MX)
- Supremin (PH)
- Umine (NZ)
- Weltmine (KP)
References
- ^ Incb.org (PDF file)
- ^ Rothman RB, Baumann MH, Dersch CM, et al. (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID 11071707.
- ^ http://www.fda.gov/bbs/topics/news/new00575.html
- ^ a b "Phentermine". Merck & Co., Inc.. 2008 . http://www.merck.com/mmpe/lexicomp/phentermine.html . Retrieved 2008-05-15 .
-
^
Nelson DL, Gehlert DR (February 2006). "Central nervous system biogenic amine targets for control of appetite and energy expenditure".
Endocrine
29
(1): 49–60. doi:10.1385/ENDO:29:1:149
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