Describe the pharmacology of suxamethonium.
This was a level 1 pharmacology question, and it represents core knowledge. The mechanism of action of suxamethonium and the interactions at the neuromuscular junction as well as pharmaceutics were areas that often required further detail. Few candidates mentioned the effects of suxamethonium on the autonomic nervous system. Another common omission related to the factors that reduce plasma cholinesterase activity beyond genetic deficiency (such as liver disease, renal failure, thyrotoxicosis). Pleasingly, there was generally a good understanding of role, dosing, side effect profile, pharmacokinetics and of special situations and limitations of use pertinent to this drug
It must be said that potentially "few candidates mentioned the effects of suxamethonium on the autonomic nervous system" because completely opposite effects are given, depending on which textbook one has been reading. For example, suxamethonium has been reported to cause tachycardia due to some poorly defined ganglionic sympathomimetic effects, or bradycardia due to direct cholinergic muscarinic effects. Face with this, trainees have the option of a) reporting both bradycardia and tachycardia, to risk looking baffoonish, or b) picking one, and risking being wrong, or c) mentioning neither, and scoring no marks, but retaining self-respect.
Anyway:
| 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 which results in delayed clearance of suxamethnium. 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, metaclopramide, cocaaine, MAOIs, or the oral contraceptive pill). |
| Elimination | Minimal renal or hepattic 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.