Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical pharmacology of neuromuscular blocking agents is described. During neuromuscular blockade, succinylcholine attaches to receptors in the motor end plate and depolarizes the neuromuscular junction, making the end plate refractory to acetylcholine. The nondepolarizing relaxants have a structure similar to that of succinylcholine and bind to the same receptors. Instead of depolarizing the junction, they block acetylcholine from binding to the receptor and cause channel blockade. As the concentration of nondepolarizing relaxant increases relative to acetylcholine, neuromuscular transmission is compromised. This relationship is used clinically to facilitate recovery from nondepolarizing agents. Succinylcholine is popular because its onset is faster than that of the nondepolarizing relaxants and metabolism by pseudocholinesterase clears it quickly. It is commonly given as an i.v. bolus to facilitate tracheal intubation. The onset of these agents varies widely and is dose dependent. Large doses are usually given to hasten the onset of paralysis; subsequent doses are adjusted according to response. The nondepolarizing agents interact with inhaled anesthetics, magnesium, and many antimicrobials. Drugs like neostigmine, edrophonium, and pyridostigmine antagonize neuromuscular blockade; an anticholinergic drug is typically administered to counteract the cardiovascular effects. The most serious adverse effects of succinylcholine are malignant hyperthermia syndrome, masseter muscle rigidity, and bradycardia. Some nondepolarizing relaxants (atracurium, mivacurium, and pancuronium) are associated with histamine release, occasionally causing serious hypotension and tachycardia. Neuromuscular blocking agents are essential to anesthesia. Older compounds produce greater toxicity than newer compounds, and several of these older compounds therefore are no longer in clinical use.
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PMID:Clinical pharmacology of neuromuscular blocking agents. 1043 10

Pharmacogenetics seeks to elucidate the variations in individual's genetic sequences in order to better understand the differences seen in pharmacokinetics, drug metabolism, and efficacy between patients. This area of research is rapidly accelerating, aided by the use of novel and more economical molecular technologies. A substantial evidence base is being generated with the hopes that in the future it may be used to generate personalised treatment regimens in order to improve patient comfort and safety and reduce incidences of morbidity and mortality. Anaesthetics is an area of particular interest in this field, with previous research leading to better informed practice, specifically with regards to pseudocholinesterase deficiency and malignant hyperthermia. In this review, recent pharmacogenetic data pertaining to anaesthetic drugs will be presented and possible future applications and implications for practice will be discussed.
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PMID:Pharmacogenetics and anaesthetic drugs: Implications for perioperative practice. 2677 37