Suxamethonium or succinylcholine is a depolarizing muscle relaxant related to acetylcholine. It is used in anesthesia to induce temporary relaxation of muscles. In doing so, it acts at the Ach nicotinic receptor (acetylcholine receptor) of the muscular endplate, where it leads to permanent depolarization.
What is suxamethonium?
Suxamethonium (chemical name: 2,2′-[(1,4-dioxobutane-1,4-diyl)bis(oxy)]bis(N,N,N-trimethylethanaminium)) is an analog of curare, a potent neurotoxin. Suxamethonium is a depolarizing muscle relaxant and acts as an agonist at the muscular nicotinic Ach receptor. In this regard, it is the only depolarizing muscle relaxant used in human medicine. Acetylcholine is normally a neurotransmitter released by nerve cells at the synapses to muscle cells to induce depolarization and thus movement of the muscle. In the process, acetylcholine is broken down again just as quickly as it binds on the receptors. Succinylcholine has a similar effect to acetylcholine, but the difference is that it is not broken down again and thus causes continuous depolarization. The muscle relaxes after a while, which is why suxamethonium is often used in anesthesia to relax patients so that they can then be ventilated, since the drug also affects the respiratory muscles. Suxamethonium is the salt of succinic acid (succinate), which is esterified at both ends with a choline residue. This results in two positive charges. For this reason, suxamethonium is presented with two negatively charged chloride ions to achieve a neutral state.
Pharmacological effects on the body and organs
Acetylcholine serves as a neurogenic transmitter of intercellular communication. It is packaged in vesicles in motor neurons and is released into the synaptic cleft in response to a signal. In doing so, it binds to nicotinic receptors in the muscular endplate. Successful binding results in the opening of a channel coupled to the receptor to which acetylcholine binds. This channel allows mainly positively charged ions such as sodium and potassium, but also negatively charged chloride ions to pass. These flow along a gradient, either into or out of the muscle cell. This results in the typical ion current. Because the gradient for sodium leading into the cell is the largest, the muscle cell becomes more and more positively charged, since sodium is a positively charged ion. The cell depolarizes, creating what is known as an excitatory postsynaptic potential (EPSP for short). When this EPSP reaches a certain threshold potential, an action potential can be generated. This action potential propagates further along the muscle and eventually leads to muscle twitching via further processes. To terminate depolarization at the muscular endplate, acetylcholine is cleaved by acetylcholinesterase. The cleavage products are reabsorbed into the nerve cell. Suxamethonium has a similar structure to acetylcholine, i.e. the above-mentioned sequence of a muscle twitch is exactly the same. The only difference is that suxamethonium is not broken down by acetylcholinesterase. As a result, it remains bound to the muscular receptor and permanent depolarization occurs. Normally, after a depolarization, the receptor is transferred to an inactive state from which it recovers after a short time and is again ready for another depolarization. However, due to the permanent depolarization, the receptor remains in the inactive state, and excitation block occurs. An initial muscle twitch is followed by relaxation.
Medical application and use for treatment and prevention.
Suxamethonium finds use as a depolarizing muscle relaxant primarily in anesthesia. It is mainly used for when short-lasting relaxations of muscles are needed. This is because suxamethonium has a short duration of action of only 10 minutes, but the onset of action is noted after only one minute. For longer operations, repeated use of suxamethonium is necessary. It is used for intubation during induction of anesthesia because it makes it easier to insert the tube into the trachea. In addition, suxamethonium is used to relax ventilated patients.It is also used in anesthesia as the drug of choice for induction of anesthesia in patients who are not fasting, which increases the risk of vomiting and aspiration of gastric contents. This is referred to as rapid sequence induction. Another indication is to reduce muscle contractions during seizures. Genetic variants of pseudocholinesterase pose a problem. This enzyme degrades suxamethonium and thus resolves muscle relaxation. One in 2500 patients has too low a level of pseudocholinesterase due to a genetic defect. As a result, suxamethonium takes longer to work in affected individuals and they need to be ventilated for a correspondingly longer period of time. Suxamethonium is administered as an injection solution.
Risks and side effects
Some patients are less able to break down suxamethonium because they lack the enzyme pseudocholinesterase. This results in life-threatening muscular blocks of the respiratory muscles. The brief muscle twitches at the onset of suxamethonium administration can cause the death of several muscle cells, depending on their strength. Potassium in the cells may leak out, leading to cardiac arrhythmias as well as other cardiovascular problems. Other side effects include an increase in intraocular pressure, which is why it should not be used in cases of known glaucoma. Some patients complain of muscle pain that lasts for days after surgery, resembling sore muscles. In these rare cases, administration of suxamethonium leads to malignant hyperthermia. It is characterized by the fact that a permanent contracture of the muscle fibers massively increases the body temperature. For this reason, patients with muscle diseases (such as muscular dystrophy) should not be treated with suxamethonium. Suxamethonium should also not be used in patients who have an unstable cell membrane, for example, due to burns and injuries. Long-immobilized patients should also avoid the drug because it increases the sensitivity of Ach receptors.
