2013C04 Describe how suxamethonium and non-depolarising neuromuscular blocking agents
produce their adverse cardiovascular effects.

Pathophysiology

·   Suxamethonium NMJ nAChR agonism -> Na⁺ influx, K⁺ efflux -> plasma K⁺ ↑0.5mM

·   Denervation -> ↑↑extra-junctional receptors (γ-ε substitution)-> ↑ duration of opening -> ↑K⁺ release

·   e.g. burns, new spinal cord injury

·   Highest risk 1-10 weeks after insult

ECG findings

·   ECG Tall tented T waves, small/absent P waves, wide QRS, sine wave, asystole

Treatment

·   Stabilize the sarcolemma: calcium gluconate

·   Lower [K⁺]: insulin/glucose, salbutamol, frusemide etc

Pathophysiology

·   Direct effect on mast cells. Non-IgE mediated

·   Degranulation of mast cells

·   H₁ (G_q):

o  Vasodilatation, capillary leak, ↓mAP

o  ↓AV node conduction, coronary vasoconstriction

o  Bronchoconstriction

·   H₂ (G_s):

o  ↑contractility, coronary vasodilatation

o  Bronchodilatation

o  Prevention: antihistamine, slower injection

·   ↓Severity with repeat doses due to depletion of mast cells

Culprits

·   d-Tubocurarine > mivacurium, atracurium

Structure-activity relationship

·   ↑Methoxy groups = ↑potency, ↓histamine release

·   e.g. mivacurium 2, atracurium 4, doxacurium 6

Pathophysiology

·   Histamine release, IgE-mediated

·   1st exposure: antigen presented to T_H cell -> B cell produces IgE -> fixes on mast cells

·   2nd exposure: systemic degranulation, vasodilatation, capillary leak, angioedema, bronchospasm

·   Muscle relaxant-induced anaphylaxis is often severe and life-threatening

Culprits

·   ~1/2000 suxamethonium

·   ~1/2500 rocuronium

Structure-activity relationship

·   Due to quaternary NH₄⁺ compound

·   ? Cross reaction pholcodine and rocuronium

Suxamethonium

·   Agonist at m2AChR

·   Esp sinus bradycardia, AV block, asystole

·   Due to affinity for cardiac mAChR

·   Risk factors: big dose >2mg/kg, young children, AV node pathology

·   Rx: atropine

Aminosteroids

·   Vecuronium: agonist at m2AChR -> ↓HR (rare)

·   Pancuronium: antagonist at m2AChR -> ↑HR (common)

·   Rocuronium: minimal effect

Culprit

·   d-tubocurarine

Structure-activity relationship

·   ↑Risk if short interonium distance

Pathophysiology

·   ↓SNS and ↓PSNS ganglionic activity

·   Often ↓HR, ↓mAP