muscle relaxants pharmacology

Question 1

what is the structure of nicotinic receptors

Answer 1

pentameric - alpha, beta, gamma, delta and epsilon
contain 2 alpha units that bind to ACh
M2 lines the pore - negative charged so cation selective

Question 2

what are nicotinic receptors

Answer 2

ligand gated ion channels - fast excitatory synaptic transmission (muscle, ganglionic and CNS types)

Question 3

what are the agonists for nicotinic receptors

Answer 3

usually non-selective - ACh/nicotine
suxamethonium is the only selective one

Question 4

what are the two mechanisms that drugs have to cause neuromuscular blocking

Answer 4

1. competitive inhibition of nicotinic receptors
2. agonist depolarising block

Question 5

how do drugs cause competitive inhibition of nicotinic receptors

Answer 5

nAChR antagonists - tubocurarine
competitive non-depolarising block

Question 6

how do drugs cause depolarising block at nicotinic receptors

Answer 6

 Nicotine, ACh, Suxamethonium
 Act as an agonist and cause an action potential, post ganglionic neuron with depolarise – no further action potential can be fired until sodium channels return to resting state
 Not competitive – increase in agonist will exacerbate effect
 Persistent stimulation leads to phase II block

Question 7

how are non-depolarising muscle relaxants used in clinic

Answer 7

tubocurarine - no longer used - severe hypotension/histamine
Pancuronium- long acting
Vencuronium – intermediate acting Mivacurium – short acting
Used for muscle relaxation in surgeries

Question 8

how are depolarising nictonic agonists used in practice

Answer 8

o Produce transient muscle twitching (fasciculations) - agonists, move to neuromuscular block caused by maintained depolarisation of muscle cells
o Suxamethonium

Question 9

what is suxamethonium

Answer 9

 Only nicotinic R agonist drug used clinically
 When fast, brief neuromuscular block is required
 Broken down by plasma cholinesterase’s
 Prolonged paralysis is a potential side effect in neonates, patients with liver disease or genetic variants lacking cholinesterase activity