Succinylcholine toxicity

Carboxylesterases include cholinesterase (pseudocholinesterase), arylcarboxyesterases, liver microsomal carboxylesterases, and other unclassified liver carboxylesterases. Cholinesterase hydrolyzes oholihe-like esters (succinylcholine) and procaine as well as acetylsalicylic acid. Genetic variant forms of cholinesterase have beeh idehtified in human serum (e.g., succinylcholine toxicity when administered as ganglionic blocker for muscle relaxation). Meperidine is hydrolyzed only by liver microsomal carboxylesterases (Fig. 10.19). Diphenoxylate is hydrolyzed to its active metabolite, diphenoxylic acid, within 1 hour (Fig. 10.19). Presumably, the peripheral pharmacological action of diphenoxylate is attributed to zwitterionic diphenoxylic acid, which is readily eliminated in the urine. 

Decreased cigarette consumption in smokers, easier to stop smoking Exaggerated response to warfarin and phenytoin Increased efficacy of omeprazole, increased toxicity of mephenytoin Absence of codeine efficacy, no effect of encainide, increased levels of tricyclic antidepressants, fluoxetine, phenothiazines Sustained paralysis to succinylcholine, possible increased toxicity of cocaine Unknown... 

Toxic symptoms may be dose-dependent and merely an exaggeration of the therapeutically desirable response, e.g., the coma of barbiturate overdosage and persistence of muscular paralysis after succinylcholine administration, or an unpredictable effect of the drug upon an organ or tissue remote from that upon which the therapeutic effect is manifested. 

Neuromuscular blocking drugs (ie, succinylcholine) are occasionally used to attenuate the peripheral (motor) manifestations of convulsions associated with status epilepticus or local anesthetic toxicity. Although this approach is effective in eliminating the muscular manifestations of the seizures, it has no effect on the central processes because neuromuscular blocking drugs do not cross the blood-brain barrier. 

Succinylcholine Agonist at nicotinic acetylcholine (ACh) receptors, especially at neuromuscular junctions depolarizes may stimulate ganglionic nicotinic ACh and cardiac muscarinic ACh receptors Initial depolarization causes transient contractions, followed by prolonged flaccid paralysis depolarization is then followed by repolarization that is also accompanied by paralysis Placement of tracheal tube at start of anesthetic procedure t rarely, control of muscle contractions in status epilepticus Rapid metabolism by plasma cholinesterase normal duration, 5 min Toxicities Arrhythmias hyperkalemia transient increased intraabdominal, intraocular pressure postoperative muscle pain... 

This occasional toxicity is due to a deficiency in the hydrolysis of succinylcholine therefore the parent drug circulates unchanged for longer periods of time and consequently... 

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