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KEY CONCEPTS

KEY CONCEPTS

  • Image not available. The primary clinical use of cholinesterase inhibitors is to reverse nondepolarizing neuromuscular blockers.

  • Image not available. Acetylcholine is the neurotransmitter for the entire parasympathetic nervous system (parasympathetic ganglions and effector cells), parts of the sympathetic nervous system (sympathetic ganglions, adrenal medulla, and sweat glands), some neurons in the central nervous system, and somatic nerves innervating skeletal muscle.

  • Image not available. Neuromuscular transmission is blocked when nondepolarizing muscle relaxants compete with acetylcholine to bind to nicotinic cholinergic receptors. The cholinesterase inhibitors indirectly increase the amount of acetylcholine available to compete with the nondepolarizing agent, thereby reestablishing neuromuscular transmission.

  • Image not available. Acetylcholinesterase inhibitors prolong the depolarization blockade of succinylcholine.

  • Image not available. Any prolongation of action of a nondepolarizing muscle relaxant from renal or hepatic insufficiency will probably be accompanied by a corresponding increase in the duration of action of a cholinesterase inhibitor.

  • Image not available. The time required to fully reverse a nondepolarizing block depends on several factors, including the choice and dose of cholinesterase inhibitor administered, the muscle relaxant being antagonized, and the extent of the blockade before reversal.

  • Image not available. A reversal agent should be routinely given to patients who have received nondepolarizing muscle relaxants unless full reversal can be demonstrated or the postoperative plan includes continued intubation and ventilation.

  • Image not available. Newer quantitative methods for assessing recovery from neuromuscular blockade, such as acceleromyography, may further reduce the incidence of undetected residual postoperative neuromuscular paralysis.

  • Image not available. Sugammadex exerts its effects by forming tight complexes in a 1:1 ratio with steroidal neuromuscular blocking agents.

  • Image not available. Cysteine causes inactivation of gantacurium via metabolic degradation and adduct formation.

Incomplete reversal of neuromuscular blocking agents and residual postprocedure paralysis are associated with morbidity; therefore, careful evaluation of neuromuscular blockade and appropriate pharmacological antagonism are strongly recommended whenever muscle relaxants are administered. Image not available. The primary clinical use of cholinesterase inhibitors is to reverse nondepolarizing neuromuscular blockers. Some of these agents are also used to diagnose and treat myasthenia gravis. More recently, newer agents, such as cyclodextrins and cysteine, with superior ability to reverse neuromuscular blockade from specific agents, are being employed or investigated. This chapter reviews cholinergic pharmacology and mechanisms of acetylcholinesterase inhibition and presents the clinical pharmacology of commonly used cholinesterase inhibitors (neostigmine, edrophonium, pyridostigmine, and physostigmine). It concludes with a brief description and mechanisms of action of new reversal agents.

CHOLINERGIC PHARMACOLOGY

The term cholinergic refers to the effects of the neurotransmitter acetylcholine. Acetylcholine is synthesized in the nerve terminal by the enzyme cholineacetyltransferase, which catalyzes the reaction between acetylcoenzyme A and choline (Figure 12–1). After its release, acetylcholine is rapidly hydrolyzed by acetylcholinesterase (true cholinesterase) into acetate and choline.

FIGURE 12–1

The synthesis and hydrolysis of acetylcholine.

Image not available. Acetylcholine is the neurotransmitter for the entire parasympathetic nervous system (parasympathetic ganglions and effector cells), parts of the sympathetic nervous system (sympathetic ganglions, adrenal medulla, and sweat glands), some neurons in the ...

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