When Do the Side Effects of a Medicine Outweigh the Symptoms of a Disease?

Almost everyone who has used medication for various illnesses has also experienced the disappointment of a need to stop treatment due to side effects that proved worse than the original symptoms. Though annoying, and often quite discouraging, the fact is that the patient at least becomes aware of the danger and is able to choose between the side effects and the symptoms. However, this is not always the case. Some medications produce side effects, which are insidious. The patient feels better, but hasn't the foggiest idea that side effects produced by the treatment are developing, which may, in the long run, result in more serious damage than that produced by the original illness. Perhaps one of the more striking examples of this dilemma is the current development of resistant strains of microbes created by antibiotics that fail to kill off the strongest germs. These germs, now relatively unopposed by other strains, create progenies that gradually become more and more resistant. Today certain antibiotics, like penicillin, have become virtually useless for treating some diseases.

Side effects may also be highly detrimental within a fairly short time-period. This takes me back to the early days of using methotrexate as a treatment for psoriasis. One of my first patients who received the drug rapidly developed a dangerously low white blood cell count. Had we not checked the blood in time and stopped the methotrexate we risked losing him. Yet, he had absolutely no idea that there was anything wrong, and was quite disappointed to learn that treatment would have to be terminated immediately, even though his rather severe psoriasis had virtually melted away.

The seriousness of the side effects created by a drug may be even less apparent if they occur without any noticeable change in laboratory studies. This is true of the antibiotics and is also true of the corticosteroids. The corticosteroids are well known for their side effects, the more profound of which develop rather slowly, but can be disastrous in the long run. On the other hand, these powerful hormones are capable of reversing severe symptoms such as those due to arthritis, skin diseases, asthma, allergies, etc. Due to the "side effects" drawback, numerous attempts have been made to minimize them by applying the medication directly to the affected area in order to avoid internal distribution. But the corticosteroids can present a terrible enigma because their effect is often so potent that severe, even permanent, changes may occur at the site of application. Furthermore, given time, local absorption sufficient to create internal damage may result anyway.

In recent years, attempts have been made to diminish the local and systemic side effects of corticosteroids that have been applied to the skin or mucous membranes by altering their chemical structures. One such drug, fluticasone proprionate, has drawn a great deal of attention because of its apparently safe utilization with good symptomatic results in the treatment of sinusitis. Its ability to decrease the inflammatory response and reduce mucosal swelling, so that drainage and aeration improve, had originally promised truly beneficial results, but studies in the past have disagreed as to the impact on a clinical outcome. The objective of a study called the "Ceftin and Flonase for Sinusitis (CAFFS) Trial," published by Dolor and colleagues in the December 26, 2001 JAMA , was to combine the antibiotic Ceftin with the intranasal corticosteroid Flonase in an attempt to improve the speed and rate of recovery of acute rhinosinusitis in patients with a history of chronic or recurrent sinus symptoms. Ceftin is the brand name for cefuroxime axetil and Flonase is the brand name for fluticasone proprionate. The study was properly conducted using a double blind, randomized, placebo-controlled multicenter approach on 95 patients. The results were fairly impressive since the addition of fluticasone proprionate provided clinical success in 93.5% of patients compared to only 73.9% of patients receiving the antibiotic alone.

Unfortunately, no effort was made to determine whether the repeated use of such a combination in patients prone to constantly recurring episodes of their rhinosinusitis could eventually result in resistance to the antibiotic and/or deleterious effects of the corticosteroid either locally or internally. There appears to be little doubt that the misery of rhinosinusitis can be dramatically alleviated this way. Perhaps this relatively new corticosteroid will prove completely safe even after many years of usage. Nevertheless, the question remains; Are you willing to take the chance today in order to achieve rapid satisfaction or would you rather wait about 10 or 20 years to find out if serious consequences might appear? Of course, by that time, new and better ways of treating may have been discovered to obviate the need for waiting.