indication

For the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous obesity.

pharmacology

Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.

mechanism of action

Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.

toxicity

Manifestations of acute overdosage with methamphetamine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.

biotransformation

Hepatic. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine.

absorption

Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3.13 to 6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta.

half life

The biological half-life has been reported in the range of 4 to 5 hours.

route of elimination

Excretion occurs primarily in the urine, the rate of which is dependent on urine pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine.

drug interactions

Chlorpromazine: Decreased anorexic effect, may increases psychotic symptoms

Fluoxetine: Risk of serotoninergic syndrome

Fluphenazine: Decreased anorexic effect, may increase psychotic symptoms

Fluvoxamine: Risk of serotoninergic syndrome

Guanethidine: Methamphetamine may decrease the effect of guanethidine.

Isocarboxazid: Possible hypertensive crisis

Mesoridazine: 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 pyschotic symptoms

Promethazine: Decreased anorexic effect, may increase pyschotic symptoms

Propericiazine: Decreased anorexic effect, may increase pyschotic symptoms

Rasagiline: Possible hypertensive crisis

Terbinafine: Terbinafine may reduce the metabolism and clearance of Methamphetamine. Consider alternate therapy or monitor for therapeutic/adverse effects of Methamphetamine if Terbinafine is initiated, discontinued or dose changed.

Thioridazine: Decreased anorexic effect, may increase psychotic symptoms

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

Trandolapril: Methamphetamine may reduce the efficacy of Trandolapril.

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

Trifluoperazine: Decreased anorexic effect, may increase psychotic symptoms

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