Phentermine

Phentermine is a drug primarily used as an appetite suppressant. Chemically, it is an amphetamine (and a phenethylamine). It is typically prescribed for individuals who are at increased medical risk because of their weight, as opposed to cosmetic weight loss. Phentermine is sold either as an immediate-release formulation (Adipex®) or as a slow-release resin (Ionamin®, Duromine® in Australia and New Zealand).

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.

Although Fen-Phen was never approved by the FDA the agency did approve of the drug. A study was published in 1992 that Fen-Phen was more effective than diet and exercise with few side effects. 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.

Phentermine is still available by itself in most countries, including the U.S. However, because it is an amphetamine, individuals may develop an 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. In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act.

Mechanism of action
Phentermine, like many other prescription drugs, works with neurotransmitters in the brain. It is a centrally-acting stimulant and is a constitutional isomer (not to be confused with stereoisomer) of methamphetamine. It stimulates neuron bundles to release a particular group of neurotransmitters known as catecholamines; these include dopamine, epinephrine (also known as adrenalin), and norepinephrine (noradrenaline). The anorectic activity seen with these compounds would thus seem likely due to this effect on the central nervous system, which is consistent with current knowledge about central nervous system systems 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.

Clinical use
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. 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. Due to the risk of insomnia, it is generally recommended that the drug be taken either before breakfast or 1-2 hours after breakfast.

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, increased alertness, 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, individuals taking this drug on a long-term basis may develop euphoria and a psychological addiction to it.

Contraindications
Phentermine should generally be avoided in patients with:
 * Agitation
 * Allergy/Hypersensitivity to other sympathomimetic amines
 * Atherosclerosis
 * Cardiovascular disease
 * Glaucoma
 * High blood pressure
 * Hyperthyroidism
 * History of drug abuse

Additionally, this drug should not be used at the same time or within 14 days following the use of monoamine oxidase inhibitors.

In the News
On March 7, 2007, Detroit Pistons guard Lindsey Hunter was suspended 10 games without pay by the NBA after testing positive for phentermine.