Methylphenidate: Difference between revisions
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| pregnancy = Category C | | pregnancy = Category C | ||
| legal = Schedule II | | legal = Schedule II | ||
| intro = '''Methylphenidate''' is a piperidine-derivative central nervous system stimulant and the most widely prescribed | | intro = '''Methylphenidate''' is a piperidine-derivative central nervous system stimulant and the most widely prescribed med for attention-deficit hyperactivity disorder. First synthesized by Leandro Panizzon at Ciba in 1944 (and reportedly named "Ritalin" after his wife Rita, who used it), it has been clinically available since the mid-1950s. Mechanistically, methylphenidate is a pure norepinephrine–dopamine '''reuptake''' inhibitor — distinct from the amphetamines, which primarily ''release'' monoamines via reverse transport. This pharmacologic difference contributes to a somewhat smoother subjective profile and slightly lower abuse liability per milligram, though methylphenidate remains a Schedule II controlled substance with meaningful misuse potential. Multiple formulations exist (immediate-release, several extended-release oral preparations, a transdermal patch, and a chewable/liquid), allowing duration-of-action to be matched to clinical need. | ||
| pharmacokinetics = '''Absorption:''' Rapid oral absorption; peak plasma levels in 1–2 hours for IR. Bioavailability is only ~30% due to extensive first-pass metabolism. Food modestly delays but does not significantly reduce absorption. The transdermal patch (Daytrana) bypasses first-pass and produces somewhat higher and steadier serum levels per dose. '''Distribution:''' Volume of distribution ~13 L/kg; plasma protein binding ~15%. Crosses the blood–brain barrier. '''Metabolism:''' Primarily metabolized by '''carboxylesterase 1 (CES1)''' in the liver — not by cytochrome P450 enzymes — to ritalinic acid, which is pharmacologically inactive. This metabolic route makes methylphenidate relatively free of CYP-mediated | | pharmacokinetics = '''Absorption:''' Rapid oral absorption; peak plasma levels in 1–2 hours for IR. Bioavailability is only ~30% due to extensive first-pass metabolism. Food modestly delays but does not significantly reduce absorption. The transdermal patch (Daytrana) bypasses first-pass and produces somewhat higher and steadier serum levels per dose. '''Distribution:''' Volume of distribution ~13 L/kg; plasma protein binding ~15%. Crosses the blood–brain barrier. '''Metabolism:''' Primarily metabolized by '''carboxylesterase 1 (CES1)''' in the liver — not by cytochrome P450 enzymes — to ritalinic acid, which is pharmacologically inactive. This metabolic route makes methylphenidate relatively free of CYP-mediated med interactions, distinguishing it from amphetamines. '''Stereochemistry:''' Methylphenidate has two stereocenters; the d-threo enantiomer carries essentially all pharmacologic activity. Dexmethylphenidate ([[Focalin]]) is the isolated d-threo enantiomer and is roughly twice as potent per milligram. '''Elimination:''' ~90% renally excreted as ritalinic acid; ~1% unchanged. Half-life of the parent compound is 2–3 hours, hence the need for extended-release formulations or multi-dose-daily schedules for sustained effect. | ||
| pharmacodynamics = Methylphenidate binds to and competitively inhibits the dopamine transporter (DAT) and norepinephrine transporter (NET), blocking reuptake of these monoamines from the synaptic cleft. Unlike amphetamines, methylphenidate is '''not a substrate''' for the transporters — it doesn't enter the presynaptic terminal, doesn't displace dopamine from vesicles, and doesn't induce reverse transport. The result is increased extracellular dopamine and norepinephrine without the additional vesicular release amphetamines produce. | | pharmacodynamics = Methylphenidate binds to and competitively inhibits the dopamine transporter (DAT) and norepinephrine transporter (NET), blocking reuptake of these monoamines from the synaptic cleft. Unlike amphetamines, methylphenidate is '''not a substrate''' for the transporters — it doesn't enter the presynaptic terminal, doesn't displace dopamine from vesicles, and doesn't induce reverse transport. The result is increased extracellular dopamine and norepinephrine without the additional vesicular release amphetamines produce. | ||
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* Consider ECG if cardiac risk factors are present | * Consider ECG if cardiac risk factors are present | ||
* At each visit: blood pressure, heart rate, weight (and height in children), efficacy, side effects, signs of misuse/diversion, tic emergence | * At each visit: blood pressure, heart rate, weight (and height in children), efficacy, side effects, signs of misuse/diversion, tic emergence | ||
* Periodically reassess continued need; consider | * Periodically reassess continued need; consider med holidays in children to assess ongoing benefit and minimize growth-velocity effects | ||
* Sleep quality and timing of last dose | * Sleep quality and timing of last dose | ||
| counseling = * Take in the morning; avoid afternoon dosing to minimize insomnia. | | counseling = * Take in the morning; avoid afternoon dosing to minimize insomnia. | ||
* '''Do not crush, chew, or split extended-release tablets/capsules.''' | * '''Do not crush, chew, or split extended-release tablets/capsules.''' | ||
* '''Concerta:''' the osmotic tablet shell will appear intact in stool — this is normal and does not mean the | * '''Concerta:''' the osmotic tablet shell will appear intact in stool — this is normal and does not mean the med wasn't absorbed. | ||
* Eat regular meals despite appetite suppression; weigh periodically. | * Eat regular meals despite appetite suppression; weigh periodically. | ||
* Stay well-hydrated. | * Stay well-hydrated. | ||