indication

For use as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.

pharmacology

Methylphenidate is a central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine.

mechanism of action

Methylphenidate blocks dopamine uptake in central adrenergic neurons by blocking dopamine transport or carrier proteins. Methylphenidate acts at the brain stem arousal system and the cerebral cortex and causes increased sympathomimetic activity in the central nervous system. Alteration of serotonergic pathways via changes in dopamine transport may result.

toxicity

Symptoms of overdose include vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes. LD₅₀=190mg/kg (orally in mice)

biotransformation

Hepatic, methylphenidate is metabolized primarily by de-esterification to ritalinic acid (α-phenyl-2-piperidine acetic acid, PPAA), which has little to no pharmacologic activity.

absorption

Readily absorbed in a biphasic manner. It reaches peak absorption at approximately two hours for the first phase and five hours for the second phase. Bioavailability is low (approximately 30%)

half life

2.4 hours in children and 2.1 hours in adults

drug interactions

Carbamazepine: Carbamazepine may decrease the effect of methylphendiate.

Cyclosporine: Methylphenidate increases the effect and toxicity of cyclosporine

Guanethidine: Methylphenidate may decrease the effect of guanethidine.

Isocarboxazid: Possible hypertensive crisis with this combination

Phenelzine: Possible hypertensive crisis with this combination

Rasagiline: Possible hypertensive crisis with this combination.

Trandolapril: Methylphenidate may antagonize the antihypertensive effect of Trandolapril. Monitor for changes in blood pressure if Methylphenidate is initiated, discontinued or dose changed.

Tranylcypromine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of Methylphenidate. Concomitant therapy is contraindicated.