ADVERSE REACTIONS TO DRUGS

 

The beneficial effects of drugs are coupled with the inescapable risk of untoward effects. The morbidity and mortality from these untoward effects often present diagnostic problems because they can involve every organ and system of the body and are frequently mistaken for signs of underlying disease. Major advances in the investigation, development, and regulation of drugs ensure in most instances that drugs are uniform, effective, and relatively safe and that their recognized hazards are publicized. However, prior to regulatory approval and marketing, new drugs are tested in relatively few patients who tend to be less sick and to have fewer concomitant diseases than those patients who subsequently receive the drug therapeutically. Because of the relatively small number of patients studied in clinical trials, and the selected nature of these patients, rare adverse effects may not be detected prior to a drug’s approval, and physicians therefore need to be cautious in the prescription of new drugs and alert for the appearance of previously unrecognized adverse events. Often, these adverse reactions are rare, such as hematologic abnormalities, arrhythmias, hepatitis, or renal dysfunction. In these cases, often (but inappropriately) labeled “idiosyncratic,” elucidating underlying mechanisms can assist development of safer compounds or allow a patient subset at especially high risk to be excluded from drug exposure. National adverse reaction reporting systems, such as those operated by the U.S. Food and Drug Administration (suspected adverse reactions can be reported online at http://www.fda.gov/medwatch/report/hcp.htm) and the Committee on Safety of Medicines in Great Britain, can prove useful. The publication or reporting of a newly recognized adverse reaction can in a short time stimulate many similar such reports of reactions that previously had gone unrecognized. Occasionally, “adverse” effects may be exploited to develop an entirely new indication for a drug. Unwanted hair growth during minoxidil treatment of severely hypertensive patients led to development of the drug for hair growth. Sildenafil was initially developed as an antianginal, but its effects to alleviate erectile dysfunction not only led to a new drug indication but also to increased understanding of the role of type 5 phosphodiesterase in erectile tissue. These examples further reinforce the concept that prescribers must remain vigilant to the possibility that unusual symptoms may reflect unappreciated drug effects.

The large number and variety of drugs and herbal remedies available OTC as well as by prescription make it impossible for patient or physician to obtain or retain the knowledge necessary to use all drugs well. It is understandable, therefore, that many OTC drugs are used unwisely by the public and that restricted drugs may be prescribed incorrectly by physicians.

Some 25 to 50% of patients make errors in self-administration of prescribed medicines, and these errors can be responsible for adverse drug effects. Elderly patients are the group most likely to commit such errors, perhaps in part because they consume more medicines. Onethird or more of patients also may not take their prescribed medications. Similarly, patients commit errors in taking OTC drugs by not reading or following the directions on the containers. Physicians must recognize that providing directions with prescriptions does not always guarantee compliance.

In hospital, drugs are administered in a controlled setting, and patient compliance is, in general, ensured. Errors may occur nevertheless—the wrong drug or dose may be given or the drug may be given to the wrong patient—and improved drug distribution and administration systems are addressing this problem. On the other hand, there are no easy means for controlling how ambulatory patients take prescription or OTC drugs.

Source: Harrison_s_Principles_of_Internal_Medicine_16th_Edition