Mechanism of action and clinical presentation
Suxamethonium binds to $N_M$-cholinergic receptors of the skeletal muscle endplate as an agonist. Like endogenous acetylcholine, it causes depolarization of the postsynaptic membrane. However, the drug is resistant to synaptic acetylcholinesterase and is practically not degraded in the synaptic cleft. Prolonged presence of the substance in the synapse provokes persistent membrane depolarization, making the conduction of new nerve impulses impossible.
Clinically, the drug's action proceeds in two phases:
- Fasciculation phase: initial muscle twitching due to the primary contraction of muscle fibers.
- Myorelaxation phase: complete relaxation of skeletal musculature.
Interaction with anticholinesterase agents
The most important rule: anticholinesterase agents (e.g., neostigmine) are not antagonists of suxamethonium. On the contrary, they exhibit pronounced synergy, enhancing and prolonging the neuromuscular block.
Potentiation of the effect occurs in two ways:
- At the receptor level: inhibition of the enzyme increases the concentration of endogenous acetylcholine, which does not eliminate the block but merely deepens membrane depolarization.
- At the metabolism level: anticholinesterase drugs block plasma cholinesterase (pseudocholinesterase), the only enzyme capable of hydrolyzing suxamethonium into choline and succinic acid.
Spectrum of application and the "dual block" phenomenon
The drug is used exclusively for short-term muscle relaxation (up to 10 minutes). It is used in anesthesiology for tracheal intubation, endoscopic procedures (bronchoscopy, cystoscopy), short surgical interventions (reduction of dislocations, repositioning of bone fragments), and for stopping tonic convulsions in tetanus.
With frequent repeated administrations of suxamethonium, the "dual block" phenomenon may develop. Desensitization of $N_M$-cholinergic receptors occurs, and the depolarizing block is replaced by an antidepolarizing (nondepolarizing) one. Only in this unique phase can the administration of anticholinesterase agents weaken the myoparalytic effect of the drug.
Side effects and contraindications
The use of suxamethonium is associated with a high risk of adverse events and severe muscular complications, including rhabdomyolysis and myoglobinemia.
- Myalgia: postoperative muscle pain occurs due to microtrauma of muscles during the fasciculation period.
- Electrolyte disturbances: the efflux of $K^+$ ions from cells during persistent depolarization leads to hyperkalemia, creating a risk of fatal arrhythmias and cardiac arrest.
- Autonomic reactions: stimulation of M-cholinergic receptors causes bradycardia and hypersalivation, while excitation of N-cholinergic receptors in sympathetic ganglia causes arterial hypertension.
- Ophthalmological effects: tonic contraction of extraocular muscles disrupts the outflow of intraocular fluid, increasing intraocular pressure.
The most dangerous complication is malignant hyperthermia. This is a life-threatening massive release of calcium ions from the sarcoplasmic reticulum (especially when combined with halothane), which leads to tonic muscle spasm and a temperature spike up to 42 °C. Dantrolene, a calcium release blocker, is used for treatment.
Due to the extensive spectrum of adverse reactions, the drug is strictly contraindicated in glaucoma, liver function impairments (the site of pseudocholinesterase synthesis), anemia, pregnancy, and infancy.
Briefly: answers to topical questions
What side effects does suxamethonium cause?
Suxamethonium causes systemic autonomic reactions, specific muscular and severe complications.
- Myalgia — postoperative muscle pain caused by muscle microtrauma.
- Respiratory depression — development of apnea.
- Hyperkalemia — efflux of potassium ions from cells, creating a risk of arrhythmias and cardiac arrest.
- Arterial hypertension — occurs due to the stimulation of N-cholinergic receptors.
- M-cholinomimetic action — manifests as bradycardia and increased salivary gland secretion.
- Ophthalmological effects — increased intraocular pressure due to contraction of extraocular muscles.
- Severe muscular complications — rhabdomyolysis and myoglobinemia.
- Malignant hyperthermia — a life-threatening condition with a sharp temperature spike and tonic muscle contraction.
In which diseases and conditions is suxamethonium absolutely contraindicated?
Suxamethonium is contraindicated in a number of diseases and physiological conditions due to the high risk of severe complications.
- Glaucoma — due to the risk of increased intraocular pressure.
- Liver function impairments — as this is the site of synthesis of pseudocholinesterase, which degrades the drug.
- Anemia — is a direct contraindication to administration.
- Pregnancy — the use of the drug is prohibited.
- Infancy — is also included in the strict list of contraindications.
It is easy to remember the development of the block by analogy with a burned-out light bulb: first, it flashes briefly and brightly (phase of muscle fasciculations), and then goes out completely, failing to respond to the supply of current (phase of persistent depolarization and myorelaxation).
Class and exam questions
What to do in case of prolonged apnea due to genetic pseudocholinesterase deficiency?
It is necessary to perform a fresh citrated blood transfusion, as it contains active pseudocholinesterase capable of cleaving suxamethonium.
Can anticholinesterase agents be used to reverse a depolarizing block?
No, they are strictly contraindicated, as they will only enhance and prolong the action of suxamethonium. The only exception is the development of the "dual block" phenomenon.
Why is suxamethonium not degraded in the synaptic cleft?
The drug is resistant to the action of tissue (synaptic) acetylcholinesterase and is hydrolyzed exclusively by blood plasma cholinesterase (pseudocholinesterase).
What else to study on this topic
- Comparative characteristics of depolarizing and nondepolarizing muscle relaxants
- Pathogenesis of malignant hyperthermia and mechanism of action of dantrolene
- Causes and mechanisms of the "dual block" phenomenon
- The effect of genetic enzymopathies on the pharmacokinetics of suxamethonium
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