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Phentermine
Acxion

  • Dapex / Phentercot / Suprenza / Teramine / Zantryl
  • WGT001
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Phentermine is a sympathomimetic amine anorectic agent and it was introduced in 1959 as part of an anti-obesity combination drug. It is chemically related to amphetamine and it is commonly referred to as an atypical amphetamine.

Phentermine has not been reported an addictive potential which allows this agent to be classified under the Schedule IV drugs (low abuse potential). Phentermine was approved in combination with topiramate in 2012 as a new alternative that required lower doses of phentermine to obtain the desired effect.

Phentermine is indicated, alone or in combination with topiramate, as a short-term adjunct, not pass a few weeks, in a regimen of weight reduction based on exercise, behavioral modifications and caloric restriction in the management of exogenous obesity for patients with an initial body mass index (BMI) greater than 30 kg/m2 or greater than 27 kg/m2 in presence of other risk factors such as controller hypertension, diabetes or hyperlipidemia.

Exogenous obesity is considered when the overweight is caused by consuming more food than the person activity level warrants. This condition commonly causes an increase in fat storage. It is an epidemic condition in the United States where over two-thirds of adults are overweight or obese and one in three Americans is obese. In the world, the incidence of obesity has nearly doubled.

It is reported that the main mechanism of action of phentermine is the generation of appetite suppression, maybe due to the increase in leptin, but it is considered that other mechanisms should be involved.

Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure.

In clinical studies where phentermine was used as a monotherapy and as combination therapy, this drug has shown an average weight loss of 3.6 kg when compared with the placebo in 2-24 weeks. Patients treated with phentermine also showed increased maintenance of the weight after treatment discontinuation.

As well, even though it is a derivative of the amphetamines, it has not been registered to produce any of the effects of amphetamine such as central nervous system stimulation, elevation of blood pressure, tachyphylaxis or QTc prolongation.

Phentermine is an indirect-acting sympathomimetic agent that acts by releasing noradrenaline from the presynaptic vesicles in the lateral hypothalamus. This increase in noradrenaline concentration in the synaptic cleft results in the stimulation of beta2-adrenergic receptors. Phentermine is classified as an indirect sympathomimetic due to the increase in the level of norepinephrine, dopamine and its indirect effect towards serotonin.

Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger. This combined effect produces a continuous flight-or-fight response in the body which reduces the hunger signal as this state is on the immediate need for energy.

Lastly, some reports have indicated that phentermine is a weak inhibitor of monoamine oxidase but this mechanism does not tend to produce a clinically significant response.

Metabolism: Phentermine undergoes minimal p-hydroxylation, N-oxidation and N-hydroxylation followed by conjugation. The total proportion of the drug that goes under metabolism only represents about 6% of the administered dose where about 5% is represented by the N-oxidized and N-Hydroxylated metabolites.

Absorption: Phentermine shows a dose-dependent pharmacokinetic profile. After oral administration of a dose of 15 mg, the maximal concentration was achieved after 6 hours and its bioavailability was not affected by the consumption of high-fat meals. The reported plasma concentration at steady-state is of around 200 ng/ml as observed in clinical trials.

Route of elimination: Phentermine is excreted mainly in the urine from which about 70-80% of the administered dose can be found as the unchanged drug.

Half life: The mean terminal half-life of phentermine is reported to be of approximately 20 hours. In conditions where there is acidic urine (pH<5), the elimination half-life is of 7-8 hours.

All medicines may cause side effects, but many people have no, or minor, side effects.Some medical conditions may interact with Phentermine.

Tell your doctor or pharmacist if you have any medical conditions.

The reported LD50 after oral administration of phentermine in rats is reported to be of 151 mg/kg. Reports of acute overdose include restlessness, tremors, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations and panic state followed by fatigue, and depression. In the cardiovascular system, there are reports of tachycardia, arrhythmia, hypertension, hypotension, circulatory collapse. In the GI tract, there are symptoms of nausea, vomiting, diarrhea and abdominal cramps. The management of acute overdosage includes symptomatic treatment as well as lavage and sedation with barbiturates

On the other hand, chronic overdosage is marked by dermatoses, insomnia, irritability, hyperactivity and personality changes. In severe cases, it can derive into a schizophrenia-like psychosis. Studies regarding the carcinogenic potential have not been performed. On the case of mutagenic assays, phentermine was shown to not be mutagenic nor clastogenic.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

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