Compare and contrast the pharmacology of suxamethonium and rocuronium.
Suxamethonium is a level 1 drug and therefore requires a detailed knowledge of the drug from a PK and PD perspective as well as consideration of important side effects and considerations when used. The examiners commented that a table structure with the structured pharmacology headings and clear concise facts was the best way to approach this question. Answers that scored poorly often displayed incorrect facts, limited appreciation of side effects and vague statements on the pharmacological particularities of this drug. For example, muscle relaxants are major culprits for anaphylaxis in hospitals, and nuanced facts about this were generally missing from candidate’s answers.
| Name | Rocuronium | Suxamethonium |
| Class | Non-depolarising NMJ blocker | Depolarising NMJ blocker |
| Chemistry | Aminosteroid | Bis-choline esther |
| Routes of administration | IV or IM only | IV or IM only |
| Absorption | Poor absorption; minimal oral bioavailability | Poor absorption; minimal oral bioavailability |
| Solubility | pKa=7.96; good water solubility | pKa=at least 13.0; good water solubility; basically insoluble in lipid |
| Distribution | VOD=0.27L, 46% protein-bound | VOD=0.14L/kg, 20% protein-bound |
| Target receptor | Nicotinic acetylcholine receptors at the neuromuscular junction | Nicotinic acetylcholine receptors at the neuromuscular junction |
| Metabolism | Minimal metabolism (less than 1%) | 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, cocaine, MAOIs, or the oral contraceptive pill). |
| Elimination | around 90% is cleared by being excreted into bile, and the rest is cleared renally | Minimal renal or hepattic clearance |
| Time course of action | Half-life 60-100 minutes | Half-life 1-2 minutes (duration of action 5-6 minutes) |
| Mechanism of action | Nondepolarising neuromuscular junction blocker (competitive antagonist of acetylcholine); by binding to the nicotinic acetylcholine receptor, this agent blocks the binding of acetylcholine, and prevents the cation channel from opening, thus preventing the depolarisation of the motor endplate. | Depolarising neuromuscular junction blocker (non-competitive partial agonist of the nicotinic receptor). 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 | Nondepolarising neuromuscular junction blockade; also: - Basically no ganglionic effects - Minimal vagolytic effect (slight increase in HR) - Minimalsympathomimetic effect (slight increase in HR) - No histamine release - Some risk of anaphylaxis (incidence is 1:3,500 to 1:445,000). |
Depolarising neuromuscular junction blockade; also a series of adverse effects: - Masseter spasm - Bradycardia (direct muscarinic effects) , or tachycardia (ganglionic sympathomimetic 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 | Wicks (1994) | Lee (2009) |
Wicks, TERRY C. "The pharmacology of rocuronium bromide (ORG 9426)." AANA journal 62.1 (1994): 33-38.
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.