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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