Drugs For Myasthenia gravis

Question 1

Anticholinesterase in myasthenia gravis

Edrophonium
Neostigmine
Pyridostigmine

Answer 1

Moa: reduce breakdown of neuronally released Ach by inhibiting cholinesterase; enhance neuromuscular transmission in skeletal and smooth muscles

Indication: myasthenia gravis, reversal of neuromuscular blockade by non depolarising neuromuscular blockers

Precautions
Contraindicated in intestinal or urinary obstruction
Asthma, cardiovascular disorders,seizures, Parkinson’s disease, peptic ulcers- risk of aggravation

Renal: use cautiously as drug is mainly renally excreted

Preg: seek specialist advice
Bf: maybe safe to use contact pregnancy drug info centres

Common adr: increased salivation, nausea,vomiting, diarrhoea, abdominal cramps.

Overtreatment may lead to cholinergic crisis with increased cholinergic effects leading to excessive sweating, involuntary defecation,urination,miosis,bradycardia, hypotension

Pyridostigmine is given orally and slower in onset but longer acting than neostigmine. It has fever cholinergic adverse effects and first line tx for myasthenia gravis

Neostigmine is given parenterally and used for neonatal myasthenia, reversal of neuromuscular blockade induced by non depolarising neuromuscular blockade & tx if myasthenia gravis when oral tx is inappropriate

Practice points
- Atropine(0.25mg IM/IV) or oral propantheline maybe needed to minimise muscarinic AE at the beginning of tx but should not be given routinely as it may mask signs of overtreatment

• transient resistance may occur after prolonged tx, decrease dose of withdraw drug for several days under medical supervision

Question 2

Neostigmine

Answer 2

Indication:
Myasthenia Gravis
Reversal of neuromuscular blockade induced by non depolarising neuromuscular blockers

Precaution
Recent anastomotic surgery- risk of leakage ;effect on GI and urinary tract motility attenuated by co administration of anticholinergic, use with caution

Dose

Myasthenia gravis
Adult s/c,IM 1-2.5mg at suitable intervals during the day. Usual total daily dose 5-20mg

Reversal of neuromuscular blockade
Give simultaneously with anticholinergic agent such as atropine or glycopyrronium to prevent muscarinic effects esp bradycardia

Adult IV :50-70mcg/kg up to 5mg
Child IV:50mcg/kg up to 2.5mg

Practice points
- when given IV for reversal of ⁶neuromuscular blockade, acts within 1 minute and last for 20-30min
-Neostigmine is marketed postoperative urinary retention and intestinal atony, but should not be used for th pp

Question 3

Pyridostigmine

Answer 3

Indication: myasthenia gravis
Dosage
Adult: titrate dose according to response

Conventionally tablet: initially 19mh TDs
Cr: 180mg-540mg (1-3 tablets od-bd)

Renal impairment; clcr less than 50ml/min titrate carefully 20-35% of normal dose