Adverse drug reactions predictability

Meanwhile, these chemicals—like chemical agents encountered at work or in hobbies or as pollutants in air, water, soil, or food—can also cause harm. Sometimes the known mechanisms of action permit us to predict the nature of toxicity to be expected. A meta-analysis of prospective studies from U.S. hospitals indicates that 6.7% of in-patients have serious adverse drug reactions 0.3% have fatal reactions (Lazarou et al., 1998). In fact, estimates of 40,000 to 100,000 deaths per year attributed to errors in medical care, primarily due to adverse reactions to pharmaceuticals, make this phenomenon a major cause of death in the United States (Meyer, 2000). A tremendous... 

There have been several attempts over the years to classify adverse drug reactions, primarily based on the perception of what can and what cannot be predicted given knowledge of the pharmacology and toxicology of the drug. For example, Edwards and Aronson [13] proposed what is probably the most extensive classification system ... 

There is considerable confusion in the use of terminology in this area. Edwards and Aronson proposed the following definition. An adverse drug reaction is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention... 

Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure. ChemMedChem, 2, 861-873. 

It is an exdting sdentific challenge to develop predictive methods that capture off-target-related adverse drug reactions reliably with a comparatively small number of compounds and at a reduced number of targets to be screened. The perfect scenario of a full data matrix as a starting point was outlined in the first part of this chapter. 

Serum chemistry markers play an important role in hepatotoxicity evaluation in human and animal safety studies. The classic markers of hepatotoxicity are alanine aminotransferase (ALT), aspartate aminotrasnferase (AST) and alkaline phosphatase (ALP) [124—127]. Drug-induced hepatotoxicity can be difficult to assess in some circumstances. Hepatotoxic responses can be intrinsic (predictable, dose-related) or idiosyncratic (unpredictable, non-dose-related). ALT, AST and ALP are generally not useful for predicting idiosyncratic responses. The administration of some drugs, such as isoniazid, can lead to a high incidence of ALT elevation, but are tolerated by most patients without severe hepatotoxicity. Adverse drug reactions can be masked... 

One of the main messages of the 2001 American Association of Cancer Research meeting was this variability in response to drugs can lead to therapeutic failure or adverse drug reactions in individuals or subpopulations of patients [12]. It is now recognized that all patients do not react in the same way to chemotherapy, but in some cases treatment response can be predicted. Pharmacogenetics provides the opportunity to tailor drug treatments and decrease uncertainties of therapy. 

Even for established excipients, regulators will look carefully at their presence in new drug formulations because they are not necessarily inert materials and some have well-established activity and/or toxicity. Clinically relevant adverse reactions are known for well-known excipients and the subject is covered elsewhere in the published literature (2,20,75-81). Findings tend to be uncommon compared to the overall prevalence of adverse drug reactions and often involve hypersensitivity reactions that are not likely to be predicted by conventional toxicity studies. 

Guzey, C., and Spigset, O. (2004). Genotyping as a tool to predict adverse drug reactions. Curr. Top. Med. Chem. 4 1411-1421. 

A medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm while medication is in the control of a healthcare professional/ patient/ or consumer (6). Not all medication errors reach the patient. These are often referred to as "near misses." They are not usually considered to be ADEs only because no harm was done. Preventable ADEs are a subset of medication errors that cause harm to a patient (7). Figure 26.1 depicts the relationship between ADES/ medication errorS/ and adverse drug reactions (8). Because adverse drug reactions are generally unexpected/ they are not presently considered to be a reflection of medication use quality in a classic sense. However/ as genetic variances become a more prominent consideration in drug selection and monitoring/ it may be possible to predict and avoid some of the reactions that have been previously unexpected. This offers an opportunity to improve the quality of medication use. 

Ingelman-Sundberg M. Pharmacogenomic biomarkers for prediction of severe adverse drug reactions. N Engl J Med 2008 358 637-9. 

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