Elsevier

Clinics in Liver Disease

Volume 21, Issue 1, February 2017, Pages 73-87
Clinics in Liver Disease

Adverse Drug Reactions: Type A (Intrinsic) or Type B (Idiosyncratic)

https://doi.org/10.1016/j.cld.2016.08.005Get rights and content

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Key points

  • Type A, or intrinsic, adverse drug reactions are dose-related, predictable toxic effects of medications, such as acute liver failure resulting from acetaminophen overdose.

  • Type B or idiosyncratic adverse drug reactions are less related to dose and are associated with drug, patient, and environmental risk factors, which can be difficult to predict.

  • Resources such as LiverTox assist with earlier detection of idiosyncratic adverse reactions in postmarketing use and can help guide diagnosis and

Type A (intrinsic) adverse drug reactions

Adverse drug reactions classified as Type A, or intrinsic, are defined as predictable adverse effects associated with an agent and are related to dose.7 As the dose of the administered agent increases, the risk of adverse event increases with it, in accordance with the pharmacologic profile of the agent.7, 8 Type A adverse effects are predictable side effects and may also be characterized as drug toxicities. Because of their predictable nature, Type A adverse effects generally have relatively

Type B (idiosyncratic) adverse drug reactions

Type B adverse drug reactions, or idiosyncratic drug reactions, are unanticipated adverse effects associated with an agent.7 They result from a combination of factors unique to the individual.5, 8, 10, 11, 12 Differences between Type A and Type B adverse drug reactions are summarized in Table 2. Although it is difficult to estimate the true incidence of idiosyncratic drug-induced liver injury due to incomplete recognition and reporting, it is thought to range from 1 in 1000 to 1 in 200,000,

Predicting drug-induced liver injury

Several methods have been used to predict the occurrence of and severity of drug-induced liver injury. The most well-known and frequently cited of these is Hy’s Law. Named for the late Dr Hyman Zimmerman, whose research and clinical insight formed much of the basis for current thinking on hepatotoxicity, Hy’s Law helps to evaluate the risk of drug-induced injury developing into ALF. Briefly, Hy’s Law is based on observations that when jaundice becomes evident in combination with drug-induced

Resources for clinicians

Initially launched in 2012, LiverTox (available at: www.livertox.nih.gov) is a free online resource that allows clinicians to access current, comprehensive information about hepatotoxicity caused by medications and to assist with diagnosis and management of drug-induced liver injury.3 The LiverTox Web site was created as a collaborative effort between the Liver Disease Research Branch of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Division of Specialized

Isoniazid

The ways in which idiosyncratic drug-induced injury is identified have evolved over time. The current architecture drug-induced liver injury monitoring in the United States is depicted in Fig. 2. Electronic resources have allowed for much quicker identification of these uncommon adverse events. The isoniazid experience demonstrates the challenges posed in identifying idiosyncratic injury in the past. Isoniazid is an antituberculosis antibiotic that causes aminotransferase elevations in about

3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors

A class of medications often linked to idiosyncratic drug-induced injury is the HMG-CoA reductase inhibitors. Commonly referred to as statins, these medications have been known to cause transient transaminitis; however, several large, randomized, prospective studies have shown that persistent aminotransferase elevations are not significantly different when compared with placebo.41, 42, 43 A retrospective review of Scandinavian patients treated with statin therapy estimated the rate of

Summary

Drug-induced liver injury is a problem associated with significant clinical impact in the United States. Classifying adverse drug events as intrinsic or idiosyncratic can help clinicians better understand the underlying mechanisms behind the response. Although intrinsic Type A response are reasonably well understood due to their predictable occurrence with increased exposure, the mechanisms and risk factors associated with Type B idiosyncratic responses are less clear. With the emergence of

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    Disclosure Statement: The authors have nothing to disclose.

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