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

· M_1,3,5: G_q GPCR (↑IP₃/↑Ca²⁺, ↑DAG)

· M_2,4: Gi GPCR (↓cAMP)

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)

Cardiovascular

· Bradycardia, AV block

· ↓Cardiac output

Respiratory

· Bronchoconstriction, ↑work of breathing

· ↑Tracheobronchial secretions

SLUDGE

· Salivation

· Lacrimation

· Urination

· Defecation

· GI upset, abdominal pain

· Emesis