indication

Used to treat attention deficit hyperactivity disorder (ADHD).

pharmacology

Amphetamines such as dextroamphetamine are noncatecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. There is neither specific evidence that clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

mechanism of action

The exact mechanism of action is not known. Dextroamphetamine stimulates the release of norepinephrine from central adrenergic receptors. At higher dosages, it causes release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems by reversal of the monoamine transporters. Dextroamphetamine may also act as a direct agonist on central 5-HT receptors and may inhibit monoamine oxidase (MAO). In the periphery, amphetamines are believed to cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming affect.

toxicity

In rats, the oral LD50 of dextroamphetamine sulfate is 96.8 mg/kg. Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states. 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 is usually preceded by convulsions and coma.

biotransformation

Hepatic.

absorption

Oral bioavailability is over 75%.

half life

10-28 hours (average is approximately 12 hours)

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: Dextroamphetamine 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

Thioridazine: Decreased anorexic effect, may increase psychotic symptoms

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

Trandolapril: Dextroamphetamine may reduce the efficacy of Trandolapril.

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

Trifluoperazine: Decreased anorexic effect, may increase psychotic symptoms

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