neostigmine (Prostigmin)

Introduction

Tradename: Prostigmin. Neostigmine bromide.

Indications

• myasthenia gravis
  • diagnostic aid
  • treatment
• neuromuscular block
  • antidote for non-depolarizing neuromuscular blocking agents, (tubocurarine, pancuronium)
• prevention & treatment of post-operative bladder distension & urinary retention

Dosage

• myasthenia gravis
  • diagnosis:
    • adults: 0.02 mg//kg IM as single dose
    • children: 0.04 mg//kg IM as single dose
  • treatment
    • 0.5-2.4 mg IM/IV/SC every 1-3 hours
    • 15-375 mg/day PO in divided every 3-4 hours
    • 15 mg PO every 3-4 hours
    • children:
      • 0.01-0.04 mg/kg IM/IV/SC every 2-4 hours
      • 2 mg/kg/day divided every 3-4 hours
• surgery:
  • dosage titrated using a peripheral nerve stimulator
  • 0.5-2.5 mg IV should antagonize most non-depolarizing neuromuscular blocks in most adults
• bladder atony: adults
  • prevention: 0.25 mg IM/SC every 4-6 hours for 2-3 days
  • treatment:
    • 0.5-1 mg every 3 hours for 5 doses after emptying bladder
• 0.6-1.2 mg of atropine or 0.2-0.6 mg of glycopyrrolate should be given a few minutes before neostigmine to counteract muscarinic effects

Tabs: 15 mg.

Injection: (methylsulfate)

• 0.5 mg/mL (1:2000) (1 mL), 1 mg/mL (1:1000) (10 mL)

Pharmacokinetics

• poorly absorbed orally (1-2%)
• peak plasma effects occur in 1-2 hours with variable duration of action
• effects on peristaltic activity occur 10-30 minutes after parenteral administration
• effects on skeletal muscle effects occur within 20-30 minutes after parenteral administration
• effects last 2.5-4 hours
• 1/2life 52-90 minutes
• metabolized in the liver, excreted in the urine

elimination via liver

elimination via kidney

Adverse effects

• common (> 10%)
  • diarrhea, increased sweating, excessive salivation, nausea, epigastric cramps
• 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
  • muscle cramps
  • fasciculations
  • hypotension

Toxicity: atropine sulfate should be available as an antagonist for effects of neostigmine

• drug adverse effects of cholinesterase inhibitors

Mechanism of action

• competitively binds to & inhibits acetylcholinesterase
• produces generalized cholinergic response
  • miosis
  • increased tone of skeletal & intestinal musculature
  • constriction of bronchi & ureters
  • bradycardia
  • stimulation of secretion by salivary & sweat glands
• quaternary ammonium salt, does not cross blood-brain barrier

More general terms

• cholinesterase inhibitor
• neurologic agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5824
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4456