Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital Long QT Syndrome (cLQTS) is an inherited disease in children and adolescents who have structurally normal hearts but present with sudden death in a high proportion of untreated patients. More than 300 mutations have been identified in 7 LQT genes. Diagnosis still depends on ECG, clinical presentations and family history. Molecular genetic testing is useful to unravel borderline family members of LQT probands, but it continues to be a research tool at present. Beta blockers remain the mainstay of treatment. ICDs are highly effective in reducing SCD for high risk patients. Gene based therapy is still preliminary. Considerable thought is needed to address and treat the asymptomatic LQT family members. The main cause of Acquired LQTS is inhibition of Ikr current, usually by drugs. Care must be taken to avoid further exposure to QT prolonging drugs or conditions. Physicians need to be aware of the pharmacodynamic and pharmacokinetic interactions of various important drugs.
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PMID:Long QT syndrome revisited. 1836 69

Psychotropics are among the most common causes of drug induced acquired long QT syndrome. Blockage of Human ether-a-go-go-related gene (HERG) potassium channel by psychoactive drugs appears to be related to this adverse effect. Antipsychotics such as haloperidol, thioridazine, sertindole, pimozide, risperidone, ziprasidone, quetiapine, olanzapine and antidepressants such as amitriptyline, imipramine, doxepin, trazadone, fluoxetine depress the delayed rectifier potassium current (IKr) in a dose dependent manner in experimental models. The frequency of QTc prolongation (more than 456 ms) in psychiatric patients is estimated to be 8%. Age over 65 years, tricyclic antidepressants (TCA), thioridazine, droperidol, olanzapine, and higher antipsychotic doses were predictors of significant QTc prolongation. In large epidemiological controlled studies a dose dependent increased risk of sudden death has been identified in current users of antipsychotics (conventional and atypical) and of TCA. Thioridazine and haloperidol shared a similar relative risk of SCD. Lower doses of risperidone had a higher relative risk than haloperidol for cardiac arrest and ventricular arrhythmia. No increased risk was identified in current users of selective serotonin reuptake inhibitors (SSRI). Cases of TdP have been reported with thioridazine, haloperidol, ziprazidone, olanzapine and TCA. Evidence of QTc prolongation with sertindole is significant and this drug has not been approved by the Food and Drugs Administration (FDA). A large trial is ongoing to evaluate the cardiac risk profile of ziprazidone and olanzapine. Selective serotonin reuptake inhibitors have been associated with QTc prolongation but no cases of TdP have been reported with the use of these agents. There are no reported cases of lithium induced TdP. Risk factors for drug induced LQT syndrome and TdP include: female gender, concomitant cardiovascular disease, substance abuse, drug interactions, bradychardia, electrolyte disorders, anorexia nervosa, and congenital Long QT syndrome. Careful selection of the psychotropic and identification of patient's risk factors for QTc prolongation is applicable in current clinical practice.
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PMID:QT alterations in psychopharmacology: proven candidates and suspects. 2021 Jul 26