Just because your doctor has given you a prescription drug for your cough or your pharmacist has recommended some one-hundred-year-old all-time favorite OTC remedy for your upset stomach does not mean you won't have a bad reaction to the medication. Unfortunately, in our less than perfect world there is just no such thing as a medication (prescription or otherwise) that cannot cause adverse reactions in some people. While the exact number of untoward reactions that occur is not known, it is estimated that the drug-related complication rate in hospitalized patients alone is between 6 percent and 15 percent. No doubt a far greater number occur at home and thus go unreported.
Nonallergic Drug Reactions
Not all adverse reactions to medications are allergic (immune-system linked) in nature. In fact, true allergies to medications probably comprise less than one-quarter of all hospital-based adverse drug reactions. The majority of unwanted effects are brought about by several non-immunologic means, including the following:
1. Direct toxic reactions
2. Impairment of the body's germ-fighting capability
3. Suppression of the body's normal protective germ population
4. Undesirable interactions between medications taken for different conditions
5. Idiosyncratic reactions
You may be wondering what practical difference it makes whether or not an adverse drug reaction (ADR) is allergic in origin. Such information is of more than just passing interest and can sometimes even be critical to a patient's life. To appreciate this, imagine that you have developed an allergy to a particular drug, and your doctor has informed you that you must never take that drug again. Now imagine that sometime afterward you fall ill with a condition that would normally necessitate treatment with that drug. If you are lucky, the condition will be one for which many different kinds of drugs have been found useful; in this instance your particular drug allergy may not be very important. On the other hand, if your condition is one for which the drug you are allergic to is the only one used for treatment or is the best one for the job, the fact that you are allergic to it may be critically important. Not uncommonly, this is the case with people who are allergic to penicillin, insulin, or the iodine-containing contrast material used in many X-ray diagnostic procedures, where no satisfactory substitutes are available.
Direct toxic reactions to medications generally result from intentional or inadvertent overdosage. Even a brief listing of the more common direct toxic reactions would fill a book much larger than this. The Physician's Desk Reference, found in many libraries and used by many physicians, is a valuable source of this kind of information. One example of a reaction is ringing in the ears; this is related to salicylism and is a common side effect of taking too much aspirin. Another reaction is vertigo, the sense of the room spinning around; this may result from an excessive dose of the antibiotic minocycline. Nausea and heart rhythm abnormalities may result from an overdose of theophylline.
Occasionally, toxic doses of a drug occur from an abnormal buildup within the body rather than from taking too much of it at one time. Since most medications are either broken down in the liver before excretion from the body or are eliminated directly through the kidneys into the urine, any coexisting damage or disease to these two organs can lead to drug overaccumulation and toxicity. For example, when the kidneys are not functioning optimally, the dose of certain diuretics (such as Lasix) must be reduced in order to prevent toxic damage to the auditory system, a situation that can lead to permanent hearing loss. Similarly astemizole (Hismanal), a popular nonsedating antihistamine that is metabolized by the liver, must be administered in much lower doses or avoided entirely in people with liver problems; otherwise, it can provoke serious heart rhythm abnormalities.
Alterations in the body's ability to fight infection or, as doctor's call it, immune system impairment is another potential nonallergic side effect of certain drugs. For example, many anticancer (antineoplastic) drugs as well as systemic corticosteroids (such as prednisone), besides their beneficial effects, unfortunately also suppress the body's natural ability to fight off infections. This leaves the patient vulnerable to a wide variety of viral, fungal, and bacterial germs. This weakened ability to fight off infection during treatment is often the direct cause of death. In addition, both kinds of drugs interfere with the body's structural repair and blood-clotting mechanisms, promoting the development of widespread black-and-blue skin rashes called purpura.
The inadvertent upset of the body's delicate equilibrium between "good" germs (those that harmlessly colonize various regions of the body) and potential troublemakers (those just waiting to cause infection) is another important drug side effect. Whether we like to believe it or not, our body cavities are ordinarily teeming with all kinds of germs that coexist in a delicate equilibrium with one another. Most benefit us by outcompeting the more harmful organisms while their own numbers remain too small to cause us any significant harm. The familiar lactobacilli that normally colonize the vagina are good examples of this type of helpful organism. Normal numbers of these bacteria prevent the overgrowth of Candida.
Problems arise when, for example, you need an antibiotic for either a gum or a urinary tract infection. At the same time the drug kills the undesirable germs in your mouth or urine, it also suppresses the populations of the "good" germs in other areas of the body, allowing "bad" ones to achieve a foothold and cause problems. The onset of yeast vaginitis in women taking penicillin, tetracycline, or erythromycin is a classic example of this scenario, which is why so many women dread taking any of these drugs. Clindamycin-associated pseudomembranous colitis is a more serious example of this kind of adverse drug reaction. By suppressing normal gut organisms, clindamycin permits the overgrowth of the toxin-producing bacteria responsible for this potentially life-threatening colon inflammation and diarrheal disease.
An idiosyncratic reaction, yet another form of nonimmunologic ADR, refers to any adverse reaction whose underlying mechanism for occurrence is unknown. Fortunately idiosyncratic drug reactions are relatively rare, but they may be provoked by even tiny amounts of a culprit medication (that is, amounts well below the therapeutic dose). Examples include the anemia caused by phenytoin (Dilantin), the widely prescribed anticonvulsant; the nerve cell inflammation seen with isoniazid (INH), currently the number one antibiotic against tuberculosis; and the bone marrow suppressive effects on red blood cell production of the broad-spectrum antibiotic chloramphenicol (Chloromycetin).
Finally, another source of nonallergic problems are undesirable medication interactions. For example, astemizole (Hismanal) and ter-fenadine (Seldane) should not be given to individuals who are taking erythromycin or ketoconazole (Nizoral). There is a significantly increased risk of provoking serious heartbeat irregularities when these agents are combined. They should also be used cautiously by anyone taking diuretics because they, too, by altering salt concentrations in the blood, also occasionally pose a risk of precipitating heart rhythm abnormalities.
These are just a few examples of the thousands of potential adverse drug interactions that a doctor must keep in mind when prescribing medications for persons with multiple medical conditions. Obviously it is extremely important to tell your doctor about any OTC or prescription medications you are taking, including headache pills and vitamins.
