Unintended effects

Compound optimization, to screen a series of therapeutic diug candidates to find the compounds that are most specific for the target protein and those that cause unintended effects, i.e. improved understanding of the molecular mode of action including structure-activity relationships for on-target versus off-target effects... 

Side effect Any unintended effect of a pharmaceutical product occurring at doses normally used in man which is related to the pharmacological properties of the drug. 

Adverse drug reaction is an undesired or unintended effect of the drug, occurs at dose normally used by human being. The adverse drug reaction requires treatment or decrease in dose if it is due to poisoning or overdose. 

Maciel (117) described the formation of the trityl cation 16 on silica-alumina in a 1984 symposium in retrospect it is surprising that no one followed up on this work until much later. 16 easily forms from triphenylcar-binol and other precursors in solutions of modest acid strength. The early observation of such an easy cation had the unintended effect of suggesting that real carbenium ions would not so easily be detected in NMR studies of solid acids. Over a decade elapsed before we characterized the rert-butyl cation on A1C13 powder (43). 

Of course, also the set of relevant alternatives has to be defined. If too many alternatives exist, a checklist approach might be used to arrive at a shortlist or a dominance analysis can be performed based on the performance matrix of the alternatives. In case of a lack of alternatives various techniques can be explored to generate additional alternatives (cf. Keeney 1992, pp. 198-240). The alternatives to be analyzed in detail should be described carefully because the way they are described can have unintended effects on decision makers preference statements. The examples provided by Tversky and Kahneman (1986) illustrate this point. 

The APA has also been busy trying to dampen, and even to obliterate, the effects of the FDA black-box warnings. A June 2007 editorial in the association s American Journal of Psychiatry (Pfeffer, 2007) lamented, these policy actions may have had the unintended effect of discouraging the prescription of antidepressants for pediatric patients and pediatric utilization of antidepressants without compensatory increases in other specific treatments (p. 845). What was the purpose of warning about suicidality, if not to discourage the use of antidepressants ... 

The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product metabolism studies should be provided in summary form. This summary should address the methodology used, the results, and a discussion of the relevance of the findings to the investigated therapeutic and the possible unfavorable and unintended effects in humans. 

The benzodiazepines are used to treat anxiety and insomnia, but they can have the unintended effects of disinhibition, rage, hostility, depression, mania, paranoia, hallucinations, nightmares, and amnesia. 

The target antigen can be expressed in nontarget tissues which can lead to unintended effects. An example is the cardiac toxicity observed in some patients treated with trastuzumab for HER2-overexpressing metastatic breast cancer.32 The mechanism of cardiac toxicity has not been fully elucidated, but it may be related to the protective role of HER2 in cardiac function.33-34... 

For many in the chemical industry these claims may sound hollow. Everyone knows that global expansion of the chemical industry, even with good faith efforts to comply with safety and pollution requirements, is assumed to carry with it adverse and unintended effects from chemical production and use. Such is the price of economic growth - correct Wrong. In fact, our passive acceptance of this paradigmatic view of the chemical industry may pose the most formidable obstacle to change. If so, the challenge may be more in our minds than our capabilities. 

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