Monday, 27 January 2014

DIAGNOSIS AND TREATMENT OF ADVERSE DRUG REACTIONS


 
The manifestations of drug-induced diseases frequently resemble those of other diseases, and a given set of manifestations may be produced by different and dissimilar drugs. Recognition of the role of a drug or drugs in an illness depends on appreciation of the possible adverse reactions to drugs in any disease, on identification of the temporal relationship between drug administration and development of the illness, and on familiarity with the common manifestations of the drugs. Many associations between particular drugs and specific reactions have been described, but there is always a “first time” for a novel association, and any drug should be suspected of causing an adverse effect if the clinical setting is appropriate.

Illness related to a drug’s intended pharmacologic action is often more easily recognized than illness attributable to immune or other mechanisms. For example, side effects such as cardiac arrhythmias in patients receiving digitalis, hypoglycemia in patients given insulin, and bleeding in patients receiving anticoagulants are more readily related to a specific drug than are symptoms such as fever or rash, which may be caused by many drugs or by other factors.

Electronic sources of adverse drug reactions can be useful (e.g., http://www.hc-sc.gc.ca/hpb-dgps/therapeut/htmleng/cadrnwsletter.html). However, exhaustive compilations often provide little sense of perspective in terms of frequency and seriousness, which can vary considerably among patients.

Eliciting a drug history from patients is important for diagnosis. Attention must be directed to OTC drugs and herbal preparations as well as to prescription drugs. Each type can be responsible for adverse drug effects, and adverse interactions may occur between OTC drugs and prescribed drugs. Loss of efficacy of oral contraceptives or cyclosporine by concurrent use of St. John’s wort are examples. In addition, it is common for patients to be cared for by several physicians, and duplicative, additive, counteractive, or synergistic drug combinations may therefore be administered if the physicians are not aware of the patients’ drug histories. Every physician should determine what drugs a patient has been taking, at least during the preceding 30 days, before prescribing any medications. A frequently overlooked source of additional drug exposure is topical therapy; for example, a patient complaining of bronchospasm may not mention that an ophthalmic beta blocker is being used unless specifically asked. A history of previous adverse drug effects in patients is common. Since these patients have shown a predisposition to drug-induced illnesses, such a history should dictate added caution in prescribing drugs.

Laboratory studies may include demonstration of serum antibody in some persons with drug allergies involving cellular blood elements, as in agranulocytosis, hemolytic anemia, and thrombocytopenia. For example, both quinine and quinidine can produce platelet agglutination in vitro in the presence of complement and the serum from a patient who has developed thrombocytopenia following use of this drug. Biochemical abnormalities such as G6PD deficiency, serum pseudocholinesterase level, or genotyping may also be useful in diagnosis, often after an adverse effect has occurred in the patient or a family member.

Once an adverse reaction is suspected, discontinuation of the suspected drug followed by disappearance of the reaction is presumptive evidence of a drug-induced illness. Confirming evidence may be sought by cautiously reintroducing the drug and seeing if the reaction reappears. However, that should be done only if confirmation would be useful in the future management of the patient and if the attempt would not entail undue risk. With concentration-dependent adverse reactions, lowering the dosage may cause the reaction to disappear, and raising it may cause the reaction to reappear. When the reaction is thought to be allergic, however, readministration of the drug may be hazardous, since anaphylaxis may develop. Readministration is unwise under these conditions unless no alternative drugs are available and treatment is necessary.

If the patient is receiving many drugs when an adverse reaction is suspected, the drugs likeliest to be responsible can usually be identified. All drugs may be discontinued at once or, if this is not practical, they should be discontinued one at a time, starting with the one that is most suspect, and the patient observed for signs of improvement. The time needed for a concentration-dependent adverse effect to disappear depends on the time required for the concentration to fall below the range associated with the adverse effect; that, in turn, depends on the initial blood level and on the rate of elimination or metabolism of the drug. Adverse effects of drugs with long half-lives take a considerable time to disappear.
Source: Harrison_s_Principles_of_Internal_Medicine_16th_Edition

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