pyridostigmine (Mestinon, Regnonol, Kalymin)

Introduction

Tradenames: Mestinon, Regonol.

Indications

• myasthenia gravis: to improve muscle strength
• useful for reversal of neuromuscular block due to non-depolarizing neuromuscular blocking agents

Dosage

• myasthenia gravis:
  • oral: 60-120 mg PO TID
  • 2 mg IM or IV slowly every 2-3 hours
  • large doses should be given with 0.6-1.2 mg of atropine IV to counteract adverse muscarinic effects
  • sustained-release: 180 mg PO QD/BID
• reversal of non-depolarizing neuromuscular blockade:
  • 10 to 20 mg slow IV
  • follow with 0.6-1.2 mg of atropine IV

Tabs: 60 mg.

Syrup: 60 mg/5 mL.

Sustained release: tabs 180 mg

Injection: 5 mg/mL (2 mL, 5 mL).

Pharmacokinetics

• quaternary ammonium salt that does NOT cross the blood brain barrier
• after IV administration, muscle strength improves within 2-5 minutes & lasts 2-3 hours
• onset of action is 15 minutes with IM injection
• undergoes hydrolysis by cholinesterase
• also metabolized in the liver by cyt P450
• patients with severe myasthenia gravis metabolize & excrete the drug faster than patients with less severe disease

elimination via liver

Adverse effects

• common (> 10%)
  • diarrhea, increased sweating, increased salivation, nausea, epigastric cramping
• less common (1-10%)
  • urge to urinate, increased bronchial secretions, miosis, lacrimation
• uncommon (< 1%)
  • thrombophlebitis, bradycardia, AV block, seizures, headache, dysphoria, drowsiness, muscle spasms, diplopia, laryngospasm, respiratory paralysis, hypersensitivity, hyper-reactive cholinergic responses, weakness
• other
  • vomiting
  • dyspnea
  • bronchospasm
  • irregular pulse
  • palpitations
  • muscular twitching
  • hypotension (rare)

• drug adverse effects of cholinesterase inhibitors

Drug interactions

• does NOT antagonize depolarizing neuromuscular blockers

• drug interaction(s) of cholinesterase inhibitors with NSAIDs
• drug interaction(s) of parasympatholytic with parasympathomimetic

Mechanism of action

• reversible anticholinesterase
• produces generalized cholinergic responses
  • miosis
  • increased tone of intestinal smooth muscle
  • bronchial constriction
  • increased salivary & sweat gland secretion

More general terms

• cholinesterase inhibitor
• neurologic agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4991
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=7550
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=134575
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=551761