Drug-induced risk

Bhatt S, Foote S, Smith A, Butler P, Steidl-Nichols J (2015) A non-human primate model for investigating drug-induced risk of orthostatic hypotension and sympathetic dysfunction pre-cUnical correlate to a clinical test. J Pharmacol Toxicol Methods 73 49-55... 

Drug-induced torsades de pointes rarely occurs inpatients without specific risk factors for the arrhythmia (Table 6—14). In most cases, administration of a drug known to cause torsades de pointes is unlikely to cause the arrhythmia however, the... 

TABLE 6-14. Risk Factors for Drug-Induced Torsades de Pointes13... 

Acute HIV Infection Diagnosis of acute HIV infection is difficult, since many patients are asymptomatic, or have nonspecific clinical symptoms similar to other common respiratory infections. If acute HIV infection is suspected, HIV antibody tests and a plasma HIV RNA concentration should be obtained. A clear diagnosis is made when an HIV antibody test is negative and the plasma HIV RNA concentration is high. There are limited outcomes data for treating acutely infected patients. Treatment of acute infection can decrease the severity of acute disease and decrease the viral set point this may decrease progression rates and reduce the rate of viral transmission.18-22 Limitations include an increased risk of chronic drug-induced toxicides and the development of viral resistance. 

There is an increased risk of drug-induced seizures in all patients treated with antipsychotics. The highest risk for antipsychotic-induced seizures is with the use of CPZ or clozapine. Seizures are more likely with initiation of treatment and with the use of higher doses and rapid dose increases. 

First, drug-induced lengthening of the QT interval has been associated with the occurrence of ventricular tachyarrhythmias, namely TdP, a polymorphous ventricular arrhythmia that may cause syncope and degenerate into ventricular fibrillation and sudden death although the incidence of TdP is a rare event (usually, less than 1 in 100 000) [32], even a low risk is not justified for drugs with uncertain benefits or drugs providing only symptomatic improvement of a mild disease. 

Use of a hERG blocker in a patient also taking drugs inducing electrolyte imbalance (e.g. risk of hypokalemia with diuretics) this is a pharmacodynamic interaction... 

A. M. (2005) HERG-Lite a novel comprehensive high-throughput screen for drug-induced hERG risk. Journal of Pharmacological and Toxicological Methods, 52, 136-145. 

Auhert, M., Osterwalder, R., Wagner, B., Parrilla, I., Cavero, I., Doessegger, L. and Ertel, E.A. (2006) Evaluation of the rahhit Purkinje fibre assay as an in vitro tool for assessing the risk of drug-induced torsades de pointes in humans. Drug Safety, 29, 237-254. 

It is agreed in this addendum that if a non-genotoxic drug induces tumours in rodents at doses above those producing a 25-fold exposure over humans, such a finding would not be considered likely to pose a relevant risk to humans. 

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