NMJ blockers

NMJ blockers: uses

paralysis of skeletal muscles during surgery to make surgical incisions easier - eliminates reflexes and spasms

used prior to intubating a patient to make insertion into the trachea easier, suppressing the gag reflex

at higher doses, the drugs can paralyze the diaphragm and intercostal muscles and cause respiratory arrest

curare

NMJ blocker used by natives of the amazon basin for hunting, coating the tips of their spears to paralyze animals

MNJ anatomy

cholinergic synapse with ACh as the NT acting at nicotinic receptors. these are N_M receptors

two major classes of NMJ blockers

non-depolarizing agents

depolarizing agents

non-depolarizing agents

classic competitive antagonist

selective for N_M receptors and do not interact to any appreciable extent with N_N at the ganglia or at muscarinic receptors (with one exception)

depolarizing agents

bind to the N_M receptor with great affinity and cause an initial depolarization and remain bound, keeping the Na channel open and preventing repolarization (paralysis)

same end point achieved as non-depolarizing

Succinylcholine

only depolarizing agent that is clinically used

non-depolarizing agents: chemistry

all are quaternary amines and ionized at all pHs

no CNS effects

given IV almost exclusively (IM works but slower onset and variable duration)

non-depolarizing agents: kinetics

onsets vary from 1-5 minutes

varying DOA based on hepatic, renal, or esterase elimination

non-depolarizing agents: reversibility

all are competitive antagonists and can be reversed by administering an AChE-I such as neostigmine

atropine is given to avoid excess stimulation of muscarinic receptors

Non-depolarizing agents: isoquinolone agents

tubocurarine (not US approved)

atracurium

cis-atracurium (predominant used in class)

non-depolarizing agents: steroid derivatives

pancuronium

rocuronium

vecuronium

Succinylcholine: chemistry

quaternary amine (always ionized)

no CNS effects

almost exclusively given IV (IM works but slower onset and variable duration)

Succinylcholine: kinetics

fast onset (1 minute)

ultra-short DOA (5-10 min) because it is metabolized by plasma and hepatic esterases (not metabolized by AChE)

Succinylcholine: reversibility

cannot be reversed by AChE-I, in fact it would prolong the blockade

Succinylcholine: uses and precautions

used for short procedures (intubation, realign a dislocated joint, facilitate bronchoscopy)

fast onset is a benefit and may be used initially for intubation followed by a longer acting NMJ blocker for the surgery

prolonged use in patients with burns and physical trauma can cause hyperkalemia by causing potassium release

Sugammadex

reversal agent

special form of gamma-cyclodextrin that sequesters NMJ blockers having the steroid nucleus (rocuronium, vecuronium, pancuronium)

greatest affinity for rocuronium, then vecuronium, then pancuronium

may reduce the efficacy of oral contraceptives

Botulinum toxin

neurotoxin produced by clostridium botulinum

causes paralysis

Botulinum toxin: clinical uses

strabismus (misaligned eyes)

focal dystonia (involuntary muscle movement or contractions)

various spastic movement disorders (eg cerebral palsy)

hypersalivation, hyperhidrosis

smoothing of lines, creases, and wrinkling all over the face, chin, neck and chest