Adverse Drug Effects premature breakdown of red blood cells (hemolysis) in subjects with a glucose6-phosphate dehydrogenase deficiency. The discipline of pharmacogenetics deals with the importance of the genotype for reactions to drugs. The above forms of hypersensitivity must be distinguished from allergies involving the immune system (p. 72). Lack of selectivity (C). Despite appropriate dosing and normal sensitivity, undesired effects can occur because the drug does not specifically act on the targeted (diseased) tissue or organ. For instance, the anticholinergic, atropine, is bound only to acetylcholine receptors of the muscarinic type; however, these are present in many different organs. Moreover,. | 70 Adverse Drug Effects Adverse Drug Effects The desired or intended principal effect of any drug is to modify body function in such a manner as to alleviate symptoms caused by the patient s illness. In addition a drug may also cause unwanted effects that can be grouped into minor or side effects and major or adverse effects. These in turn may give rise to complaints or illness or may even cause death. Causes of adverse effects overdosage A . The drug is administered in a higher dose than is required for the principal effect this directly or indirectly affects other body functions. For instances morphine p. 210 given in the appropriate dose affords excellent pain relief by influencing nociceptive pathways in the CNS. In excessive doses it inhibits the respiratory center and makes apnea imminent. The dose dependence of both effects can be graphed in the form of dose-response curves DRC . The distance between both DRCs indicates the difference between the therapeutic and toxic doses. This margin of safety indicates the risk of toxicity when standard doses are exceeded. The dose alone makes the poison Paracelsus . This holds true for both medicines and environmental poisons. No substance as such is toxic In order to assess the risk of toxicity knowledge is required of 1 the effective dose during exposure 2 the dose level at which damage is likely to occur 3 the duration of exposure. Increased Sensitivity B . If certain body functions develop hyperreactivity unwanted effects can occur even at normal dose levels. Increased sensitivity of the respiratory center to morphine is found in patients with chronic lung disease in neonates or during concurrent exposure to other respiratory depressant agents. The DRC is shifted to the left and a smaller dose of morphine is sufficient to paralyze respiration. Genetic anomalies of metabolism may also lead to hypersensitivity. Thus several drugs aspirin antimalarials etc. can provoke premature breakdown of red blood cells hemolysis .
