Suxamethonium has a longer duration of effect than acetylcholine, and is not hydrolyzed by acetylcholinesterase. By maintaining the membrane potential above threshold, it does not allow the muscle cell to repolarize. When acetylcholine binds to an already depolarized receptor, it cannot cause further depolarization. Calcium is removed from the muscle cell cytoplasm independent of repolarization (depolarization signaling and muscle contraction are independent processes). As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes. This explains muscle flaccidity rather than tetany following fasciculations. The results are membrane depolarization and transient fasciculations, followed by paralysis. Phase 2 block
While this phase is not abnormal and is a part of its mechanism of action, it is undesirable during surgery, due to the inability to depolarize the cell again. Often, patients must be on a ventilator for hours if Phase 2 block occurs. It is caused by the blood concentration of suxamethonium exceeding the therapeutic window. Desensitization occurs at the nerve terminal, and the myocyte becomes less sensitive to acetylcholine; the membrane repolarizes and cannot be depolarized again. Chemistry
Suxamethonium is an odorless, white crystalline substance. Aqueous solutions have a pH of about 4. The dihydrate melts at 160 °C, whereas the anhydrous melts at 190 °C. It is highly soluble in water (1 gram in about 1 mL), soluble in ethyl alcohol (1 gram in about 350 mL), slightly soluble in chloroform, and practically insoluble in ether. Suxamethonium is a hygroscopic compound. The compound consists of two acetylcholine molecules that are linked by their acetyl groups.
In people with neuromuscular disease or burns, an injection of suxamethonium can lead to a large release of potassium from skeletal muscles, potentially resulting in cardiac arrest. Conditions having susceptibility to suxamethonium-induced high blood potassium are burns, closed head injury, acidosis, Guillain–Barré syndrome, cerebral stroke, drowning, severe intra-abdominal sepsis, massive trauma, myopathy, and tetanus. Suxamethonium does not produce unconsciousness or anesthesia, and its effects may cause considerable psychological distress while simultaneously making it impossible for a patient to communicate. Therefore, administration of the drug to a conscious patient is contraindicated. Hyperkalemia
The side effect of high blood potassium may occur because the acetylcholine receptor is propped open, allowing continued flow of potassium ions into the extracellular fluid. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per liter. The increase is transient in otherwise healthy patients. The normal range of potassium is 3.5 to 5 mEq per liter. High blood potassium does not generally result in adverse effects below a concentration of 6.5 to 7 mEq per liter. Therefore, the increase in serum potassium level is usually not catastrophic in otherwise healthy patients. Severely high blood levels of potassium can cause changes in cardiac electrophysiology, which, if severe, can result in arrhythmias and even cardiac arrest. Malignant hyperthermia
Malignant hyperthermia (MH) from suxamethonium administration can result in a drastic and uncontrolled increase in skeletal muscle oxidative metabolism.