2016B10 Describe the effects of giving an unopposed dose of neostigmine.



·      Summary: PC, PK, PD

·      Nicotinic

·      Muscarinic




·  Quaternary ammonium charged drug, doesn’t cross BBB


·  0.05mg/kg IV, ceiling 0.07mg/kg

·  Onset 3 mins, peak 10 mins, duration 30-60 mins

·  50% metabolized (PChE, CYPs)

·  50% excreted unchanged in urine

·  t1/2β 75 mins


·  Mechanism:

o Forms reversible carbamylate complex with esteratic site of AChE

o ↑[ACh] at cholinergic synapses

o Muscarinic effects at low dose, nicotinic at high dose

o (Also inhibits PChE -> augment suxamethonium and mivacurium)


·  Use:

o Reverse non-depolarising relaxant e.g. atracurium

o Myasthaenia gravis

o Bladder atonia

o Pseudo-obstruction

o Glaucoma



Nicotinic effects:

Muscle type

·   ↑[ACh] -> ↑Na+ influx > K+ efflux = Ca2+ influx -> end-plate potential ± action potential -> contraction

·   Displace and reverse non-depolarising relaxant

o Starting TOF count 3-4: adequate reversal

o Starting TOF count 1-2: inadequate

·   Augment and prolong depolarizing relaxant (↑ACh at NMJ, also inhibits PChE!)

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

Neuronal type

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

·   Brain (α4β2): nil (quaternary amine, doesn’t cross BBB)


Muscarinic effects:

PSNS post-ganglionic

·   Receptor effects:

o M1,3,5: Gq GPCR (↑IP3/↑Ca2+, ↑DAG)

o M2,4: Gi GPCR (↓cAMP)

·   Clinical effects:

o -Bradycardia, AV block, ↓cardiac output (cardiac plexus M2).

o -Constriction of airway smooth muscle -> obstruction (airway smooth muscle M3)

o -↑Tracheobronchial secretion -> cough, aspiration (M3)

o ↑Salivation (M3)

o ↑Lacrimation (M3)

o ↑Ureteric peristalsis -> urination (treats bladder atony)

o ↑GIT peristalsis -> defecation, nausea/vomiting, abdo pain; treats pseudo-obstruction

SNS post-ganglionic

·   ↑Sweating

·   ↑Skin vasodilatation

·   ↑Skeletal muscle vasodilatation