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

1. Neuroleptic drugs (antipsychotics) produce numerous side effects which include serious extrapyramidal symptoms consisting of akathisia, dystonia, neuroleptic malignant syndrome, parkinsonian reactions such as postural abnormality, tremor, akinesia or bradykinesia, rigidity, and tardive dyskinesia. 2. Among the complications of neuroleptic chemotherapy, the most serious and potentially fatal complication is malignant syndrome, which is characterized by extreme hyperthermia, "lead pipe" skeletal muscle rigidity causing dyspnea, dysphagia, and rhabdomyolysis, autonomic instability, fluctuating consciousness, leukocytosis, and elevated creatine phosphokinase. 3. Neuroleptic malignant syndrome should be differentiated from malignant hyperthermia, lethal catatonia, and other pathological states producing some of these same symptoms. 4. In addition to neuroleptics, malignant syndrome has been caused by thymoleptics (antidepressants), metoclopramide (antiemetic), metoclopramide combined with cimetidine, tetrabenazine, overdosage of benzodiazepine, phenelzine, dothiepin and alcohol, and amphetamine. 5. Factors leading to and/or facilitating the emergence of neuroleptic malignant syndromes are reportedly organic brain syndrome, dehydration, exhaustion, external heat load, excessive sympathetic discharge, use of long acting neuroleptics, high doses of neuroleptics, rapid dose titration with neuroleptics, abrupt discontinuation of antiparkinsonism agents, and concurrent lithium therapy. 6. Although, the pathogenesis of neuroleptic malignant syndrome is not understood completely, a blockade of dopaminergic receptors in the hypothalamus, spinal cord and striatum, an alteration of dopaminergic-serotonergic transmission in the body, an enhanced synthesis and action of prostaglandin E1 and E2, and a modification of calcium-mediated signal transduction in the body have been suggested. 7. The treatment of malignant syndrome includes immediate withdrawal of neuroleptic drugs, i.v. infusion of dantrolene, and oral administration of bromocriptine; or alternatively i.v. infusion of dantrolene and the combination of levodopa-carbidopa. 8. Other measures to enhance the therapeutic effectiveness of the aforementioned regimens are to include the use of anticholinergic drugs such as benztropine to enhance the effectiveness of bromocriptine, of lorazepam if catatonic symptoms persist, or of electroconvulsive therapy (ECT) if psychotic symptoms persist. 9. These treatments, however, must be "active" rather than "passive", in order to avert fatalities and/or unfortunate sequelae from this iatrogenic and incompletely understood disease.
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PMID:Pathogenesis and treatment of neuroleptic malignant syndrome. 197 19

In the last decades, advances in molecular biology have led to modern pharmacogenetics, which started as a science that focused on investigating drug metabolising enzymes and genetic determinants of pharmacokinetic variability. As more evidence has become available on the structure of drug targets and the genes coding for them, increasing attention has been directed towards pharmacodynamic explanations of variability in therapeutic response as well as in the risk for adverse drug reactions. Traditionally, genetic drug safety research has focused on variations in single genes whose functions are known to be related to given adverse drug reactions. A few such examples, malignant hyperthermia, the long QT syndrome, venous thromboembolic disease, tardive dyskinesia, and drug addiction, are presented in this article. In the future, results from the Human Genome Project together with tools such as DNA microarray technology, high-output screening systems and advanced bioinformatics, will permit a more thorough elucidation than is currently possible of the genetic components of adverse drug reactions. By screening for a large number of single nucleotide polymorphisms (SNPs), SNP patterns associated with adverse drug reactions can be discovered even though the functions of the SNPs as such are completely unknown. On the basis of these findings, it can be expected that pharmacogenetic research will identify situations where a drug should be avoided in certain individuals in order to reduce the risk for adverse drug reactions. If so, it will be feasible to use molecular diagnostics to select drugs that are safe for the individual patient.
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PMID:Genotyping of drug targets: a method to predict adverse drug reactions? 1211 41