Describe the pharmacology of suxamethonium
Most candidates presented a structured answer and demonstrated reasonable understanding of the pharmacology of suxamethonium. This is however a core subject and candidates should be able to answer this question in depth.
Syllabus: H2a, 2c
Recommended sources: Basic and Clinical Pharmacology, Katzung, Chp 27
| Class | Depolarising NMJ blocker |
| Chemistry | Bis-choline esther |
| Routes of administration | IV or IM only |
| Absorption | Poor absorption; minimal oral bioavailability |
| Solubility | pKa=at least 13.0; good water solubility; basically insoluble in lipid |
| Distribution | VOD=0.14L/kg, 20% protein-bound |
| Target receptor | Nicotinic acetylcholine receptors at the neuromuscular junction |
| Metabolism | Metabolised by butyrylcholinesterase. Butylcholinesterase deficiency is a genetic condition that results in delayed clearance of suxamethonium. Butylcholinesterase activity may also be deficient in liver disease, renal failure, malignancy, pregnancy, in malnutrition, following cardiopulmonary bypass, or due to the effect of drugs (eg. organophosphates, neostigmine, metoclopramide, cocaine, MAOIs, or the oral contraceptive pill). |
| Elimination | Minimal renal or hepatic clearance |
| Time course of action | Half-life 1-2 minutes (duration of action 5-6 minutes) |
| Mechanism of action | By binding to and activating the nicotinic acetylcholine receptor, suxamethonium depolarises the motor endplate of the neuromuscular junction, resulting in an action potential. After the membrane is depolarised, suxamethonium maintains it in a partially depolarised state, preventing the perijunctional voltage-gated sodium channels from returning to the active state. This prevents the generation of any further action potentials, blocking the junction. |
| Clinical effects | Depolarising neuromuscular junction blockade; also a series of adverse effects: - Masseter spasm - Bradycardia (direct muscarinic effects) , or tachycardia (ganglionic sympathomimentic effect) - Increased intraocular pressure - Increased intracranial pressure - Myalgia - Fasciculations - Hyperkalemia, which may become lifethreatening in stroke, spinal injury, burns, chronic immobility, or critical illness - Increased intragastric pressure, transiently |
| Single best reference for further information | Lee (2009) |
Lee, Chingmuh. "Suxamethonium in its fifth decade." Baillière's clinical anaesthesiology 8.2 (1994): 417-440.
Lee, C. "Goodbye suxamethonium!." Anaesthesia 64 (2009): 73-81.
Gibb, David B. "Suxamethonium—A Review: Part I.—Physico-Chemical Properties and Fate in the Body." Anaesthesia and Intensive Care 1.2 (1972): 109-118.
Gibb, David B. "Suxamethonium—A Review: Part II—Neuromuscular Blocking Properties." Anaesthesia and Intensive Care 1.3 (1973): 183-201.
Gibb, David B. "Suxamethonium-A Review: Part III—Pharmacological Actions of Suxamethonium Apart from Its Neuromuscular Blocking Effect." Anaesthesia and Intensive Care 2.1 (1974): 9-26.
Torda, T. A., et al. "Pharmacokinetics and pharmacodynamics of suxamethonium." Anaesthesia and intensive care 25.3 (1997): 272-278.