Eur. J. Clin. Pharmacol. 19, 231-232 (1981) European Journal of Clinical Pharmacology © Springer-Verlag 1981

Personal View

What's Wrong With Drugs?

A. Kfildor

I. Department of Medicine and Unit of Clinical Pharmacology, Budapest, Hungary

According to the Guinness Book of World Records "Samuel Jessup, an English hypochondriac, con- sumed 226,934 pills and 40,000 bottles of medicine between a period from 1774 and 1816, nevertheless he reached a great age and died only when he was 65 years old". At the meeting of the European Regional Office of the World Health Organisation in Bonn in 1977, a drug was mentioned, which is produced in 38 forms, and is used by 31 methods according to 43 different dosage schedules [1]. So, apparently some- thing was and still is wrong with drugs.

The proof of the pudding is in the eating, the proof of a car is decided by the customer who drives it, but whether or not a drug is "good" is decided in general by a third party, the attending physician, or recently even by a fourth, the clinical pharmacologist. The patient's opinion is asked for, it is registered and computed, but the therapeutic decision concerning the individual is made by the doctor (except for non- compliance of patients, or drop-outs in trials), the actual treatment of a disease in general is decided by the clinical pharmacologist, and the destiny of a drug, too, is settled by "higher" authorities, such as scien- tific bodies, drug regulatory agencies, and the phar- maceutical industry, where economic and political aspects are also considered.

We used formerly to administer many different medicines, which chemically were not well-defined, and we thought that the response of the human organism to the effects of a drug was uniform. Nowa- days, we mostly use, or should use, well-defined synthetic preparations, and it has turned out that their metabolism and their effects are influenced by sex, race, age, degree of nutrition, environmental cir- cumstances, interaction with other compounds, and last but not least by genetic factors. Unfortunately, the consequences of these discoveries are not gener- ally taken into account in everday therapy. Individual

variations in reactions to drugs become more and more complex. Perhaps in a few years time it will be nearer to the truth just to say that Mr. X. or Ms. J. has reacted to a drug in this or that way in a given period of his or her life.

Not many years ago, a new approach to rational drug therapy was developed. Determination of the blood levels of various drugs appeared to be clinically valuable in estimation of drug effects. It turned out, however, that blood levels in several cases were not as useful as they first appeared to be; for example, "it is impossible to determine whether knowledge of the serum digoxin concentration allows to distinguish between the toxic and nontoxic subject under investi- gation to be more accurately than could have been done on clinical grounds alone" [2].

Previously, when a diagnosis was made, the "right" medicine was prescribed for the sick person, which, to our present knowledge, was in most cases ineffective, and it was given as long as the patient became well or died. The diagnosis is made much more easily nowadays, but the doctor is confronted with more complicated problems: to treat or not to treat (mild hypertension), which drug to give (bacte- rial infection), what doses to give (autoimmune dis- eases), which drug combination to give (haematolog- ical disorders) what preventive drug treatment to give (virus infections), and last but not least, the phy- sician must take into consideration the risks of stop- ping drug treatment, whether on his initiative or as a consequence of the patient's non-compliance.

A few years ago it was well known that acute withdrawal of certain drugs administered in the treat- ment of several chronic disorders might lead to sud- den deterioration in the condition of the patient, e. g. in asthma and epilepsy, and the same overshoot mechanism may be true for patients treated with anticoagulants. The doctor now faces the same prob-

0031-6970/81/0019/0231/$01.00

232 A. KS.ldor: What's Wrong With Drugs?

lem with many of his hypertensive patients, who may encounter a hypertensive crisis if they suddents stop taking their drugs. "Antihypertensive" vasodilators used in congestive heart failure, such as nitroprusside or prazosin, when suddenly withdrawn may also cause dangerous deterioration of the cardiac failure [3]. Rebound insomnia after short administration of benzodiazepines, and more severe neurological symptoms after several months administration, must be considered, too (and benzodiazepines are prob- ably the most widely used drug throughout the world). Thus, in many instances nowadays the physi- cian should 'attend' the patient when the drug is no longer taken, just as he is supposed to do when a drug is newly prescribed.

Many of us remember the occasions when the prescribing doctor did not have to think too much about the hazards of administering a new drug. Now the benefit/risk ratio is or should be in the mind of the doctor in every case, even though in most patients he will deal with non-comparable factors. As an example: what is the risk for a hypertensive patient, who is well controlled with a beta-blocker, of awak- ing after a nightmare with tachycardia, palpitation, sweating and an unknown blood pressure? Neverthe- less, a hypertensive patient must realize that he or she has to live with the untoward effects of the therapy. These patients must cope with the fact that some of their body functions will be impaired, perhaps for their entire lifetime.

Although the benefit/risk ratio is sometimes really of no practical value, its concept and expert application is one of the major contributions of clini- cal pharmacology.

Drug compliance by hypertensive patients may be very poor, because many of them are symptom-free.

It is may be reasonable to believe that drug com- pliance is much better with purely symptomatic drugs, such as certain pain-killers in rheumatism or codeine against dyspnoea, and not so good in many cases of more direct, aetiologically-directed therapy, where good compliance would do more for the patient.

Previously, anyone who was taking a medicine was considered a sick person. Nowadays many of us take some drugs regularly, whilst living normal and productive lives. The so-called "drug revolution" not only means that we have now powerful and possibly dangerous drugs with us; it may also mean that these substances are becoming part of that area of our lives that we have not yet become adapted to. Perhaps there is nothing wrong with drugs at present, but something is wrong with us.

References

1, Clinical Pharmacological Services. Report on a Working Group, Bonn. 1977. Regional Office for Europe, World Health Organi- zation, Geneva

2. Ingelfinger JA, Goldman P (1976) The serum digitalis concen- tration - Does it diagnose digitalis toxicity? N Engl J Med 294: 867-870

3. Gerber JG, Nies AS (1979) Abrupt withdrawal of cardiovascu- lar drugs. N Engl J Med 301:1234-1235

Prof. A. Kfildor, M. D. I. Department of Medicine and Unit of Clinical Pharmacology Jfinos Hospital Didsfirok-ut 1 H-1125 Budapest, Hungary