DEPOLARIZING MUSCLE RELAXANTS
Depolarizing muscle relaxants physically resemble acetylcholine (ACh), and because of this resemblance, they are able to act as competitive agonists by binding to ACh receptors (AChR) and generating action potentials.
Succinylcholine (SCh) is the only depolarizing muscle relaxant in clinical use. It is generally used when there is risk for aspiration of gastric contents or when there is need for rapid paralysis. It is essentially two ACh molecules joined together.
Because of its low lipid solubility and relative overdose, SCh has a very rapid onset of action. Onset of action is approximately 30-90 seconds and its duration of action 5-10 minutes. Succinylcholine is not metabolized by acetylcholinesterase, which is located in the neuromuscular junction (NMJ). Instead, it is metabolized by plasma cholinesterase (pseudocholinesterase), an enzyme present in the blood. Succinylcholine, therefore, has a longer duration of action at the motor end plate. This leads to prolonged depolarization known as a phase I block. Phase I block is often preceded by muscle fasciculation. This is probably the result of the prejunctional action of SCh, stimulating AChR on the motor nerve, causing repetitive firing and release of neurotransmitter. Recovery from phase I block occurs as SCh diffuses away from the NMJ and is metabolized by plasma cholinesterase in plasma.
Repeated boluses or an infusion of SCh may lead to either a desensitization block, or a phase II block. A desensitization block occurs when the continued presence of an agonist causes the AChR to become insensitive to the binding of the agonist. This is thought to be a safety mechanism to protect against overexcitation of the NMJ. With a phase II block the membrane potential is in a resting state despite an agonist being present and subsequent neurotransmission is blocked throughout. The block takes on the characteristics of a block induced by a nondepolarizing muscle relaxant (Table 59-1). Phase II block may be antagonized by anticholinesterases but the result is hard to predict. For this reason, spontaneous recovery is recommended.
TABLE 59-1Nondepolarizing Muscle Relaxants and Their Properties |Favorite Table|Download (.pdf) TABLE 59-1 Nondepolarizing Muscle Relaxants and Their Properties
|Relaxant ||Intubating Dose (mg/kg) ||Onset after Intubating Dose (Min) ||Duration (min)a ||Primary Excretion ||Metabolism ||Histamine Release ||Other |
|Short Acting |
|Mivacurium ||0.2 ||1-1.5 ||15-20 ||Insignificant ||Pseudochol inesterase ||Yes || |
|Intermediate Acting |
|Vecuronium ||0.15-0.2 ||1.5 ||60 ||75% biliary; 25% renal ||Small extent by liver ||No ||Metabolite has NMBb activity |
|Rocuronium ||0.6 ||2-3 ||30 ||>75% liver; ||None ||No || |
| ||1.2 ||1 ||60 ||<25% renal || || || |
|Atracurium ||0.75 ||1-1.15 ||45-60 ||<10% biliary + renal ||Nonspecific Esterasesc + Hofmann degradationd ||Yes ||Intermediate (laudanosine) associated with CNS excitation |
|Cisatracurium ||0.2 ||2 ||60-90 ||None ||Hofmann ||No || |
|Long Acting |
|Pancuronium ||0.08-0.12 ||4-5 ||90 ||Limited degree by liver ||40% renal;10% bile ||No ||Metabolite has NMB activity; vagolytic |
|Pipecuronium ||0.07-0.85 ||3-5 ||80-90 ||Minor hepatic ||70% renal; 20% biliary ||No || |