2016B10 Describe the effects of giving an unopposed dose of neostigmine.
List:
· Summary: PC, PK, PD
· Nicotinic
· Muscarinic
Summary:
|
Physicochemical |
· Quaternary ammonium charged drug, doesn’t cross BBB |
|
Pharmacokinetic |
· 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 |
|
Pharmacodynamic |
· 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 |