skeletal muscle relaxants and neuromuscular blocking agents

cholinergic receptors are blocked by

atropine

types of cholinergic receptors

• nicotinic (ligand gated ion channels)

• muscarinic (GPCRs)

nicotinic receptors responds to

• acetylcholine

• nicotine

muscarinic receptors respond to

• nicotine

• muscarine

list cholinergic effects

• bradycardia

• increased gastric tone (increased stomach contraction)

• bronchoconstriction

• constricted pupils

list anti-cholinergic effects

• dry mouth

• dilated pupils

• increased HR

• urinary retention

• constipation

what is organophosphate poisoning?

exposure to organophosphate leads to inhibition of AChE which increases ACh levels → overstimulation of AChR

treatment of organophosphate poisoning

• resuscitation

• oxygen

• atropine and acetylcholinesterase (pralidoxime)

skeletal muscle relaxants that work peripherally

neuromuscular blocking agents (non-depolarising/depolarising)

skeletal muscle relaxants that work centrally

muscle relaxants

name non-depolarising blocking agents

• curare (rocuronium, vercuronium)

• tubocurarine

competitive antagonists

blocks ion channel (when bound, ion channel stays closed)

mechanism of action - non-depolarising blocking agents

• competitive antagonists

• bind to presynaptic nicotinic receptors at NMJ and inhibits ACh release

• “train of four”

safe TOF ratio at neuromuscular junction

greater than 0.9

reversal of non-depolarising blocking agents

• anti-cholinesterase drugs (neostigmine, pyridostigmine)

• sugammadex

example of fast acting ND-NMBA

mivacurium

example of intermediate acting ND-NMBA

Rocuronium, Vecuronium, Atracurium.

example of long acting ND-NMBA

Pancuronium

describe anti-cholinesterase drugs

• neostigmine, pyridostigmine

• increase ACh availability at motor end plate

• increase ACh release from motor nerve terminal

• co-administrated w/ atropine due to cholinergic effects

describe sugammadex

• modified gamma cyclodextrin

• chelating agent

• no cholinergic effects

advantages of non-depolarising blocking agents

• reduces anaesthetic dose

• NDB reversible with anticholinesterases and sugammadex

• relatively few side effects

disadvantages of non-depolarising blocking agents

• need to ventilate patient

• slow speed of onset and offset

what are depolarising blocking agents

agonists at nicotinic receptors of the NMJ

examples of DNMBA

• suxamethonium (succinylcholine)

• decamethonium

mechanism of action- depolarising blocking agents (DNMBA)

• mimics ACh action at nicotinic receptors = continuous activation

• sustained depolarisation of motor endplate → desensitisation

• hydrolysed by plasma cholinesterase rapidly

phases of D-NMBA - MOA

• phase I = inactivation

• phase II = desensitisation

desensitisation

reduces responsiveness of receptor to agonist

describe suxamethonium (succinylcholine)

• short term, rapid muscle relaxation

• given after anaesthetic induction

• cannot be reversed

problems with suxamethonium (succinylcholine)

• stimulates ALL cholinergic receptors (muscarinic and nicotinic) → bradycardia

• hyperkalaemia (risk of arrhythmia)

• increased intraocular pressure

• muscle twitching

• malignant hyperthermia

list the skeletal muscle relaxants used in the clinic

• methocarbamol

• baclofen

• dantrolene

• tizanidine

describe spasticity

• skeletal muscle rigidity, exaggerated tendon jerks, paralysis of muscle

• velocity-dependent increase in tonic stretch reflexes