indication

For the treatment and management of obesity.

pharmacology

Phentermine is indicated in the management of exogenous obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction. Phentermine hydrochloride is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.

mechanism of action

Phentermine is an amphetamine that stimulates neurons to release or maintain high levels of a particular group of neurotransmitters known as catecholamines; these include dopamine and norepinephrine. High levels of these catecholamines tend to suppress hunger signals and appetite. The drug seems to inhibit reuptake of noradrenaline, dopamine, and seratonin through inhibition or reversal of the reuptake transporters. It may also inhibit MAO enzymes leaving more neurotransmitter available at the synapse.Phentermine (through catecholamine elevation) may also indirectly affect leptin levels in the brain. It is theorized that phentermine can raise levels of leptin which signal satiety. It is also theorized that increased levels of the catecholamines are partially responsible for halting another chemical messenger known as neuropeptide Y. This peptide initiates eating, decreases energy expenditure, and increases fat storage.

toxicity

LD₅₀ is adult monkeys is 15 to 20 mg/kg. Symptoms of overdose include delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, and circulatory collapse.

biotransformation

Hepatic.

absorption

Phentermine is rapidly absorbed after oral ingestion.

half life

16 to 31 hours

drug interactions

Acetophenazine: Decreased anorexic effect, may increase psychotic symptoms

Chlorpromazine: Decreased anorexic effect, may increase psychotic symptoms

Ethopropazine: Decreased anorexic effect, may increase psychotic symptoms

Fluoxetine: Risk of serotoninergic syndrome

Fluphenazine: Decreased anorexic effect, may increase psychotic symptoms

Fluvoxamine: Risk of serotoninergic syndrome

Guanethidine: Phentermine may decrease the effect of guanethidine.

Isocarboxazid: Possible hypertensive crisis

Mesoridazine: Decreased anorexic effect, may increase psychotic symptoms

Methdilazine: Decreased anorexic effect, may increase psychotic symptoms

Methotrimeprazine: Decreased anorexic effect, may increase psychotic symptoms

Paroxetine: Risk of serotoninergic syndrome

Perphenazine: Decreased anorexic effect, may increase psychotic symptoms

Phenelzine: Possible hypertensive crisis

Prochlorperazine: Decreased anorexic effect, may increase psychotic symptoms.

Promazine: Decreased anorexic effect, may increase psychotic symptoms

Promethazine: Decreased anorexic effect, may increase psychotic symptoms.

Propericiazine: Decreased anorexic effect, may increase psychotic symptoms.

Propiomazine: Decreased anorexic effect, may increase psychotic symptoms

Rasagiline: Possible hypertensive crisis

Thiethylperazine: Decreased anorexic effect, may increase psychotic symptoms

Thioridazine: Decreased anorexic effect, may increase psychotic symptoms

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trandolapril: Phentermine may reduce the efficacy of Trandolapril.

Tranylcypromine: The MAO inhibitor, tranylcypromine, may increase the vasopressor effect of the amphetamine, phentermine. Concomitant therapy should be avoided.

Trifluoperazine: Decreased anorexic effect, may increase psychotic symptoms

Triflupromazine: Decreased anorexic effect, may increase psychotic symptoms

Trimeprazine: Decreased anorexic effect, may increase psychotic symptoms

Triprolidine: Triprolidine may reduce the sedative effect of the antihistamine, Phentermine.

Venlafaxine: Risk of serotoninergic syndrome