Methylphenidate – Mechanism of Action, Side Effects and Dosing

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Methylphenidate (DAT and NAT Inhibitor):

Mechanism of action:

Methylphenidate (MPH) non-competitively blocks the reuptake of dopamine and noradrenaline into the terminal by blocking dopamine transporter (DAT) and noradrenaline transporter (NAT), increasing levels of dopamine and noradrenaline in the synaptic cleft.

 

Side Effects:

Common: Insomnia, decreased appetite, dysphoria, irritability, tics

Rare: anxiety, depression, psychosis, mania

Metabolism and Half-life:

Methylphenidate is metabolised primarily by de-esterification to α-phenyl-piperidine acetic acid (PPAA) which has little or no pharmacologic activity.

Carboxylesterase-1A1 (CES-1), located in the stomach and liver, is the primary enzyme involved with first-pass MPH metabolism.

Elimination half-life that is independent of the preparation of MPH (2.5 to 3.5 hours after oral administration

Methylphenidate Immediate Release (Ritalin)

  • Ritalin is a racemate consisting of a 1:1 mixture of d-threo methylphenidate (d-MPH) and l-threo methylphenidate (l-MPH).
  • Available as a tablet
  • Onset – 20 to 60 minutes
  • Duration of action – 2 to 4 hours.
  • Dosing – Dose initially 5 mg to 10 mg titrated up in weekly increments by 5 mg to 10 mg to a maximum of 2.1 mg/kg/day, maximum dose 60 mg daily.
  • Recommended monitoring blood pressure, pulse, appetite
  • Monitor for insomnia, mood changes and development of tics.
  • Product information from TGA. 

Methylphenidate is also available in the extended-release version.

Ritalin LA (Long-acting)

  • Ritalin LA is available in capsule form.
  • One Ritalin LA capsule contains 10 mg, 20mg, 30mg,40mg or 60 mg of methylphenidate hydrochloride.
  • Each modified-release, hard-gelatin capsule contains half the dose as immediate-release beads and the remaining half of the dose as enteric-coated, delayed-release beads. This provides an immediate release of methylphenidate followed by a delayed release of methylphenidate.
  • Duration of action – 6-8 hours
  • These beaded preparations are useful for children who cannot take or who dislike taking pills, as parents can open the capsules and sprinkle the medicine on their child’s food.
  • Product information from TGA. 

Concerta: 

  • Methylphenidate XR (Concerta) uses an osmotic release oral system (OROS) which has an osmotic pump mechanism that creates an ascending profile of MPH in the blood, providing effective treatment for up to 10 to 12 hours.
  • Approximately 25% of the methylphenidate is delivered immediately, with the remaining 75% released gradually for sustained symptomatic relief
  • Available in doses of 18 mg, 27 mg, 36 mg, and 54 mg.
  • Product information from TGA.