Canonical Question
Suxamethonium Pharmacology
Master answer
- Suxamethonium is the dicholine ester of succinic acid which acts as an ultrashort acting depolarising muscle relaxant.
- It is used in rapid sequence induction and to modify seizures caused by ECT.
- Mechanism of Action:
- mimics the actions of Ach by binding to the nicotinic Ach receptor and causing membrane depolarization.
- However, because its hydrolyzing enzyme is not present at the NMJ, the effect lasts longer than for Ach.
- The persistent depolarization renders the voltage sensitive Na channels inactive within 1-2 mins.
- This prevents the transmission of further APs. Initially causes fasciculations, then muscle relaxation.
- Partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist
- A partial agonist is unable to achieve a maximal biological response following active site binding, despite increasing doses
- A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor
- Since it induces a lower biological response on active site binding than acetylcholine, it is a non-competitive antagonist of acetylcholine at the nicotinic receptor
- No matter how high levels of acetylcholine are at the neuromuscular junction, maximal response will not be reached
Advantages and Disadvantages of Sux in ICU
| Effect | Advantage | Disadvantage |
|---|---|---|
| Pharmaceutics | Inexpensive | Needs to be stored at 4 degrees -Shelf life only 7 days when kept in resuscitation trolley |
| Can be given peripherally | ||
| Excretion of 10% of drug unchanged in urine means active metabolites may accumulate and prolong the effects. | ||
| 0.03% of population are abnormal metabolisers resulting in prolonged apnoea | ||
| Causes fasiculations | Offset of fasiculations indicates paralysis | Muscle pains |
| Causes malignant hyperthermia | ||
| Prolonged suxemethonium apnoea | If intubation fails, prolonged apnoea | |
| Some agonism at muscarinic receptor | Second dose of suxemethonium commonly causes bradycardia | |
| Widespread neural depolarisation | Hyperkalaemia Raised intraocular pressure Raised GIT sphincter pressures | |
| Rapid onset (30-60 seconds) | Short period of time before intubating conditions achieved – Less risk of desaturation / apnoea when intubating | |
| Rapid offset (5-10 minuts) | If intubation fails, apnoea will not be prolonged | Muscle paralysis may disappear before airway secured or patient made safe |
| Metabolised by plasma cholinesterase | Metabolism not dependant on organ function | Plasma cholinesterase may be lower in some patients – myriad reasons |
Mooney / JC 2020
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2012B Q02 | Suxamethonium is a non-competitive partial agonist. Explain what is meant by this statement using definitions of the underlined terms (50% of marks). List the advantages and disadvantages of suxamethonium within Intensive Care practice (50% of marks). | historical_member | — |
| 2018A Q10 | Outline the advantages (15% of marks) and disadvantages (85% of marks) of the clinical use of suxamethonium. | historical_member | — |