7.7:
Depolarizing Blockers: Pharmocokinetics
Depolarizing blockers like succinylcholine have a rapid onset, paralyzing arms, neck, legs and respiratory muscles within minutes of administration.
Following intravenous injection, succinylcholine mimics the endogenous ligand acetylcholine and binds nicotinic receptors at the motor end plates of skeletal muscles.
Although acetylcholinesterase readily hydrolyzes acetylcholine, succinylcholine is more resistant and is hydrolyzed slowly. So, it remains bound to receptors longer, prolonging membrane depolarization.
However, succinylcholine has a very short duration of action of 5-10 minutes because it diffuses away into the plasma. There, it is readily metabolized by the plasma cholinesterase into succinylmonocholine, which is further hydrolyzed into choline and succinic acid and eliminated from the body.
Such rapid hydrolysis allows only a tiny portion of the injected drug to remain available at the motor end plates.
To calculate the dose of succinylcholine required to produce adequate paralysis, plasma levels of cholinesterase are estimated from a detailed patient assessment.
7.7:
Depolarizing Blockers: Pharmocokinetics
Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which usually persist for at least 20-30 minutes.
Plasma cholinesterase also hydrolyzes some amount of injected succinylcholine, so a tiny amount of the drug can cause blockage. Patient parameters, such as body weight and current physical condition, determine succinylcholine dosage. A higher drug dose that does not pose health risks is often favored to avoid complications arising from ineffective paralysis during a surgical procedure. In addition, the rate of succinylcholine metabolism varies among individuals depending on cholinesterase activity. The presence of an abnormal cholinesterase variant can prolong succinylcholine's action and cause risk to the patient's well-being.
Dibucaine, a pseudocholinesterase inhibitor, is used to test at-risk patients. Dibucaine reduces the activity of wild-type acetylcholinesterase by 80%. However, it can reduce the action of the abnormal variant only by 20%. The dibucaine number defines the percentage inhibition of the enzyme. A dibucaine number above 70 is described as normal, intermediate if it is between 40-70, and atypical if it is below 20. Patients with a dibucaine number below 20 will go into apnea, where respiratory muscles collapse, and the patients stop breathing or remain paralyzed for about 2 hours or longer. In such cases, succinylcholine administration for any surgical process must be avoided.