2020A13 Describe the adverse effects of neostigmine



·         Pharmacodynamics

·         Nicotonic adverse effects

·         Muscarinic adverse effects



Receptor interaction

·      Forms reversible carbamylate complex with esteratic site of AChE

·      ↑[ACh] at cholinergic synapses

Receptor affinity

·      Muscarinic (G protein-coupled): effects at low dose

·      Nicotinic (ligand gated ion channel): effects at high dose

·      Also inhibits PChE -> augment suxamethonium

Receptor effects

·      N: ↑[ACh] -> ↑Na+ influx -> MEPP

·      M1,3,5: Gq GPCR (↑IP3/↑Ca2+, ↑DAG)

·      M2,4: Gi GPCR (↓cAMP)


Nicotonic adverse effects:

Muscle type

·      Weakness at high dose (ceiling 0.07mg/kg)

·      Inability to reverse profound neuromuscular blockade
-> risk of residual curarisation if used without monitoring

Neuronal type

·      Autonomic ganglia (α3β4): stimulation then depression (see BJA-Education)

·      No CNS effect (quaternary ammonium charge)


Muscarinic adverse effects:


·      Bradycardia, AV block

·      ↓Cardiac output


·      Bronchoconstriction, ↑work of breathing

·      ↑Tracheobronchial secretions


·      Salivation

·      Lacrimation

·      Urination

·      Defecation

·      GI upset, abdominal pain

·      Emesis


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