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Psuedocholinesterase Deficiency

Pseudocholinesterase Deficiency: Pathophysiology and Anesthetic Considerations Drugs (anticholinesterases) Break down or inhibit the pseudocholinesterase enzymeà↓ pseudo- cholinesterase activity Note: Pseudocholinesterase has many synonymous names including butyrylcholinesterase, BChE, BuChE, plasma esterase, plasma cholinesterase, and serum cholinesterase Malignancy Abnormal gene expressionà↓ protein synthesis Acquired Liver disease ↓ liver’s ability to synthesize proteins Malnutrition ↓ molecular precursors for protein production Renal Disease Mechanism unclear Fluid Overload Hemodilution of circulating proteins Hereditary BChE (Butyrylcholinesterase) gene mutation ↓ production or production of non-functional pseudo- cholinesterase by the liver ↓ synthesis of pseudocholinesterase by the liver Pseudocholinesterase Deficiency: reduced levels of functional pseudocholinesterase in plasma and tissues Impaired ability to hydrolyze ester linkages of substrates like neuromuscular blocking agents (e.g. succinylcholine, mivacurium, diamorphine, acetylsalicylic acid, methylprednisolone, cocaine, heroin ) Prolonged binding of neuromuscular blocking agent to nicotinic cholinergic receptors in neuromuscular junctions ↑ patient’s susceptibility to side effects from drugs with ester linkages Mivacurium administered to produce muscle paralysis Succinylcholine administered to produce muscle paralysis Competitively binds to acetylcholine nicotinic receptor Irreversibly binds to acetylcholine nicotinic receptor Active site of post-synaptic acetylcholine receptor is blocked Continuous depolarization of skeletal muscle Acetylcholine cannot act on receptor = skeletal muscle can’t depolarize Skeletal muscle unable to repolarize Skeletal muscle paralysis Acetylcholine released cannot trigger an action potential ↑ duration of muscle fiber paralysis Since respiratory muscles are affectedà Apnea requiring sedation and respiratory assistance for up to several hours Extended paralysis and/or anesthesia Authors: Evan Allarie Yan Yu* Reviewers: Stephen Chrusch Brooke Fallis Melinda Davis* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com