week 2 Flashcards
examples of non depolarising muscle relaxants
Rocuronium
Pancurnium
Vecuronium
Tubocurarine
Atracurium
mechanism of action of non depolarising muscle relaxants
Structurally similar to ACh
Antagonism of nicotinic ACh receptors (competitive inhibitor) on motor end plate, prevent ACh binding
MOA of Rocuronium
non depolarising neuromusclar blocker
competative inhibitor of the ACh at nicotinic receptor
Administration of Rocuronium
IV bolus 1.2mg/kg
onset within 45-60seconds
Distribution of Rocuronium
Rapid onset, highly ionized, small Vd
Duration 20-35 mins
metabolised in liver and excreted renally
short half life
Mechanism of action of depolarising muscle relaxants
Phase 1; depolarising
acts on nicotinic receptor and opens causing Na influx
remains bound to the receptor
persistant depolarisation prevents repetitive firing
Phase 2; desensitisation
with continued polarisation membrane will repolarise
When and why should you not use depolarising muscle relaxants
Burns, nerve damage, closed head injuries
due to potassium release caused by nicotinic channels
K release can be exaggerated and risk of cardiac arrest
Also can cause increased ocular pressure so contraindicated in open globe trauma
what effects do depolarising muscle relaxants have on skeletal muscle?
what can this cause ?
Initial fasciculations
then flaccid paralysis
myalgia common post operative
mechanism of action of Suxamethonium
Depolarising neuromuscular blockade
Phase 1 depolarising, causing fasciculation
Phase 2 continued exposure, unresponsive to subsequent impulses, causing flaccid paralysis
pharmacokinetics of suxamethonium
IV administration
onset 30-60 seconds
duration 2-8 minutes
hydrolysed rapidly by plasma pseudocholinesterase
Adverse effects of Suxamethonium
muscle pain
bradycardia with repeat dosing
release K+ - especially in burns and trauma
raised IOP and ICP
risk of malignant hyperthermia
risk of prolonged paralysis
Definition of malignant hyperthermia
A pharmacogenetic disorder of skeletal muscle triggered by certain anaesthetic agents,
leading to uncontrolled calcium release from the sarcoplasmic reticulum → hypermetabolic state.
Genetic factors of mlignant hyperthermia
Autosomal dominant inheritance.
Most commonly due to mutation in the RYR1 gene (ryanodine receptor type 1).
triggering agents for malignant hyperthermia
Volatile inhaled anaesthetics (e.g. halothane, sevoflurane, desflurane)
Succinylcholine (suxamethonium)
🚫 NOT triggered by: IV agents like propofol, opioids, benzodiazepines, ketamine, nitrous oxide.
pathophysiology of malignant hyperthermia
Defective RYR1 receptor → excessive Ca²⁺ release from sarcoplasmic reticulum → sustained muscle contraction → increased ATP consumption → heat + CO₂ + lactate production → metabolic acidosis and hyperthermia.
Leads to: rhabdomyolysis, hyperkalaemia, arrhythmias, renal failure, death if untreated.
Features of malignant hyperthermia
Early signs:
Rapid rise in end-tidal CO₂ (ETCO₂), Tachycardia, Muscle rigidity (especially masseter), Hyperkalaemia
Later signs:
Hyperthermia, Acidosis, Rhabdomyolysis (↑ CK, myoglobinuria)
🧠 For ACEM: Know why ETCO₂ rises (↑ metabolism & CO₂ production) and why muscle rigidity occurs (Ca²⁺-mediated contraction).
Management of malignant hyperthermia
Immediate cessation of triggering agent.
100% O₂ (high flow).
IV dantrolene (RYR1 antagonist – inhibits calcium release).
Dose: 2.5 mg/kg IV, repeated as needed.
Cool the patient (active cooling).
Correct acidosis, hyperkalaemia, arrhythmias.
Monitor for complications (renal failure, DIC).
