Деполяризующие блокаторы: фармакокинетика

Succinylcholine mimics acetylcholine and binds nicotinic receptors at motor end plates, causing rapid onset paralysis within minutes. Unlike acetylcholine, succinylcholine resists hydrolysis by acetylcholinesterase and remains bound to receptors longer, prolonging membrane depolarization and muscle paralysis across arms, neck, legs, and respiratory muscles.

Although succinylcholine binds receptors longer than acetylcholine, it diffuses rapidly away from the motor end plate into plasma, where plasma cholinesterase quickly metabolizes it into succinylmonocholine and then into choline and succinic acid. This rapid diffusion and metabolism limits its duration to only 5-10 minutes, leaving minimal drug available at the motor end plate.

Plasma cholinesterase is the primary enzyme responsible for metabolizing succinylcholine after it diffuses from the motor end plate into the bloodstream. The enzyme hydrolyzes succinylcholine into succinylmonocholine, which is further broken down into choline and succinic acid for elimination. Individual variations in cholinesterase activity significantly affect how quickly patients metabolize the drug.

Patients with abnormal cholinesterase variants metabolize succinylcholine much more slowly, potentially causing prolonged paralysis lasting 2 hours or longer. The dibucaine number test identifies at-risk patients by measuring enzyme inhibition: normal patients score above 70, intermediate between 40-70, and atypical below 20. Patients with dibucaine numbers below 20 may experience apnea and must avoid succinylcholine.

Succinylcholine dosage depends on patient parameters including body weight and current physical condition. Plasma cholinesterase levels are estimated through detailed patient assessment to calculate adequate paralysis doses. Higher doses are often favored when safe to prevent complications from ineffective paralysis during surgery, though individual cholinesterase activity variations must be considered.

The dibucaine number measures the percentage inhibition of pseudocholinesterase by the drug dibucaine. Dibucaine reduces wild-type enzyme activity by 80% but abnormal variants only by 20%. A dibucaine number below 20 indicates atypical cholinesterase, signaling that succinylcholine will persist dangerously long and should be avoided in surgical procedures.

Succinylcholine has a very short duration of 5-10 minutes because it rapidly diffuses into plasma and is quickly metabolized by plasma cholinesterase. In contrast, nondepolarizing competitive neuromuscular blockers persist much longer, typically 20-30 minutes or more. This difference makes succinylcholine ideal for brief procedures requiring rapid onset and offset.