Neostigmine

Question 1

How does neostigmine work?

Answer 1

• it’s an ACh-ase inhibitor
• prevents breakdown of ACh at NMJ = increased concentration of ACh, restores transmission at NMJ
• quaternary amine, similar structure to ACH, binds to acetylcholinesterase
• phenol group (in middle) breaks away so both sites of ACh-ase are occupied and can’t metabolise ACh

Question 2

What are the disadvantages of acetylcholinesterase inhibitors?

Answer 2

• not specific to NMJ so increased ACh concentration effects are also seen at muscarinic receptors
  
  • bradycardia
  • arrhythmias
  • bronchospasm
  • nausea/vomiting
  • increased gut motility
  • salivation

Question 3

What are the uses of neostigmine?

Answer 3

• reversal of neuromuscular blockade caused by non-depolarising muscle relaxants
• myaesthenia gravis
• paralytic ileus

Question 4

What is the absorption/distribution of neostigmine?

Answer 4

• poorly absorbed orally
• oral bioavailibility 1-2%
• protein binding 10%
• volume of distribution 0.4 - 1 L/kg
• max effect 7-11 mins, lasts 4 hrs
• half life - 15-18mins

Question 5

What are the CVS effects of neostigmine?

Answer 5

• bradycardia
• hypotension

Question 6

What are the RS effects of neostigmine?

Answer 6

• increased secretions
• bronchoconstriction

Question 7

What are the CNS effects of neostigmine?

Answer 7

• miosis and blurred vision
• low dose: muscle contraction
• high dose: large amounts of ACh at NMJ may block neuromuscular transmission as receptors flooded

Question 8

What are the GI effects of neostigmine?

Answer 8

• increased secretions
• peristalsis
• nausea and vomiting

Question 9

What is the dose of neostigmine?

Answer 9

0. 05mg/kg IV
   (2. 5mg + 0.5mg glycopyrrolate mixed)

Question 10

What is the metabolism and excretion of neostigmine?

Answer 10

• metabolised by plasma esterases
• small amount of hepatic metabolism, products are excreted in bile
• remainder excreted in urine