Differences in drug response are heritable. Ever since the introduction of drugs in medicine there have been problems with adverse reactions. In the absence of knowledge of the minimum effective dose, the occurrence of adverse events was even used to determine the appropriate dose of a drug. Doses were increased until adverse effects occurred. Nowadays, drugs are extensively tested in clinical studies to obtain information on the effective and safe dosage before they enter the market. Despite all these efforts not every drug is safe and beneficial for every patient. Different people may respond differently to the same drugs at the same dose in terms of efficacy of the drug, but also in the occurrence of adverse effects. For instance, as a rule of thumb, one third of people benefit from antidepressants, one third does not and one third does not take them or discontinues them (in part) because of adverse effects. Although some differences can be explained by differences in age (and the accompanying changes in metabolism), sex, organ function, concomitant therapy, drug-drug interactions and the nature of the disease, differences in reaction to drugs are often unpredictable. However, differences in efficacy and adverse effects do not occur random. It appears that differences are greater among members of a population than within the same person at different times (or between monozygotic twins). The existence of large population differences with small intra-patient variability suggests that inheritance is a determinant of drug response. It is estimated that genetics can account for 20-95% of variability in drug response. Once a drug is administered, it is absorbed and distributed to its site of action where it interacts with targets (such as receptors or enzymes), undergoes metabolism and is then excreted. At each of these processes, genetic variation may influence the drug response.

Additional Metadata
Keywords DNA, adverse drugs effects, cradiovascular diseases, drugs, genetics
Promotor B.H.Ch. Stricker (Bruno) , A. Hofman (Albert)
Publisher Erasmus University Rotterdam
Sponsor The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The contributions of the inhabitants, general practitioners and pharmacists of the Ommoord district to the Rotterdam Study are gratefully acknowledged. The studies in this thesis were supported by grant 948-00-014 from the Research Institute for Disease in the Elderly (RIDE) of the Netherlands Organization for Health Research and Development (ZonMw) and the EUDRAGENE project, EC 5th Framework grant no. QLRI-CT-2002-02757. Financial support for the publicaton of this thesis was kindly provided by: the Department of Epidemiology & Biostatistics of ErasmusMC, the Netherlands Health Care Inspectorate , the Netherlands Pharmacovigilance Fund.
ISBN 978-90-90-22900-3
Persistent URL hdl.handle.net/1765/37553
Citation
Aarnoudse, A.L.H.J. (2008, April 9). Genetic susceptibility to adverse drug effects : common variants in the ABCB1 and NOS1AP genes. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/37553