“All men are mortal,

Socrates is a man,

Therefore, Socrates is mortal.”

Syllogism (Aristotalian Logic)





Doctors who believe that there is a pill for every ill, based on their education in the medical school using the bio-medical model of diseases, will have to remember that every pill also has an ill following it. World Health Organization some years ago, in their wisdom, had published forty-two essential drugs and the list could be a bit bigger now. Unfortunately, to-date only one country, Bangla Desh, has had the courage to implement this rule in toto. The one good thing that Gen. Irshad did to his people, as a dictator, was to implement the WHO drug guidelines. India might get the dubious distinction of having the largest number of drug combinations manufactured and sold, in addition to the multitude of so-called Ayurvedic drugs, most of which are only folk medicine. The added danger is that if they label anything, as Ayurvedic the drug control is much easier. Many unscrupulous companies do that just to get out of the clutches of the control and license raj.



WHO, in its wisdom, had published a list of 43 essential drugs. In the bio-technological model of man, we doctors are brought up to believe that disease affects an organ or a few organs and could be cured by a pill or a surgical procedure. This never happens. The final healing (making it whole) has to come from the immune system of the patient. The drug or the surgical procedure will only stimulate the immune system. Consequently, drugs are not the be and end all of disease management. It is not for nothing that Oliver Wendell Holmes wrote that if the whole materia medica could be sunk to the bottom of the seas it would be that much good for mankind and worse for the fishes! Bio-medical model uses linear mathematics. Unfortunately, the human body does not follow linear mathematics; not that it does help any other system of reality in the world. The following quote from two Nobel worthy particle physicists you would convince even the converts.



As far as the laws of mathematics refer to reality, they are not certain, and as far as they are certain, they do not refer to reality.



Rothman & Sudarshan







To appreciate the role of drug vis-à-vis the role of the body's defense mechanism a bit of medical history would be useful.





Figures.







Whereas 59% of the fall in death rate occurred before the advent of anti-TB drugs, only 6% further change occurred after they were introduced. Out of that only 3% was due to ATT. Medical text books never give these figures. Similar findings are seen with many other anti-biotics.



Antibiotic Resistance:



Nearly seventy years ago, when Alexander Fleming and Prof. Florey discovered a moldy growth on their culture plates to be a powerful antibiotic, penicillin, a new era began in medicine. The predictions then were, as usual, that the end of man’s fight against germs on this planet is drawing closer. Like all other predictions in linear science this one has also been belied. Doctors have been predicting the unpredictable all these years. That in itself is not bad! But we are now facing a new and formidable threat in that many of the germs that were initially sensitive to antibiotics have now become resistant and threaten to annihilate man from this planet. One example would suffice. One common germ, the streptococcus, was the most sensitive germ to be killed by penicillin. While 95% of these germs could be easily killed by penicillin to begin with, today 95% of the same is resistant to penicillin.



The gravity of the situation is such that the Royal College of Physicians of London organized a meet to discuss the Clinical Implications of Anti-microbial Resistance on the 28th February 2001. It has been estimated that around 15,000 people die in that small country every year from infections against which no antibiotic is effective. Such of those germs that are resistant to most antibiotics are called the super-bugs and, as of now, we have no defense against them. One of the biggest hospitals in that country, Portsmouth Hospitals NHS Trust, has been forced to shut down most of its operating theatres last summer because of super-bugs there. At the Queen Alexandra Hospital the orthopedic surgeons could not perform any operation around that time. Another leading authority in the field, Professor Hugh Pennington of Aberdeen University, feels that the next big problem would be that of drug resistant tuberculosis. They had an outbreak of TB in Scotland recently, traced to a travelling family. He also feels that the Russian prisons have many inmates who have drug resistant TB without proper treatment. Since TB does not respect geographic borders this time bomb might explode anytime anywhere!



The usual thinking in the West was that this kind of uncontrolled infectious disease scenario could exist only in the poor countries like India and sub-Saharan Africa. They are now in for a great shock. In a well researched book, Betrayal of Trust: The Collapse of Global Public Health, Laurie Garrett from the USA, shows how the threat is not confined to the poor countries but, is greater in the West, basically because doctors there over-prescribe antibiotics so that bacterial infections are becoming increasingly resistant to the most widely used antibiotics. She writes that "doctors who over-prescribe antibiotics undermine the health care system by encouraging germs to become resistant." She is dead right there.



The blame must also come on the consumers, the patients, as many of the latter, who think that they are well informed, demand antibiotics for the common trivial infections, most of which are viral to begin with. This adds to the problem. Doctors who follow ethics and refuse to give antibiotics are not usually popular. The fear of losing the patients makes many doctors to oblige patients with over-prescribing. Educating the public about the serious dangers of taking antibiotics for minor infections against medical advice should go a long way in reducing this menace.



Studies have shown in the USA that it is the rich kids that suffer more from ear infections and other common childhood infections. Since antibiotics are very expensive the poor parents do not bother to give their children antibiotics for minor illnesses. This helps the child to fight the infection with the help of its own immune system and, in the bargain, the child develops immunity against major infections. This has another very dangerous ramification to it. Antibiotics given to minor viral illnesses of childhood make the immune system change its response to infection in such a way that the cytokine response to infections, based on their genes, changes from TH1 to TH2. The latter is the most important trigger for asthma in later life. The slum dwellers’ kids, when they have enough to eat, have very robust health and have very low incidence of asthma and many other common illnesses. Whenever they do not thrive, it is only because they do not get enough nutrition in their diet.



The other dangers of antibiotics are in commercial fields like farming and the diary industry. Broiler sheds use a lot of antibiotics to not only treat the infections in chicks but also in the fond hope of preventing infections in them. The amount of antibiotics used in cattle and broiler sheds far outweighs all that is used in hospitals and operation theatres! Today it takes only six weeks to get a bird on the dining table from the egg stage, about half the time normally required. The farmers, therefore, make double money and the birds come cheaper. But it means that we get a huge dose of antibiotics each time we bite a chicken lollypop! This does not take into account the added hazards of excessive hormones fed to fatten the birds. In short, we are only eating a slow poison.



Mastitis in cows is another danger. The incidence is around 10% of the cows in a diary on a given day! The huge amount of antibiotics, like ciprofloxacin, injected into the udder (one udder dose costs Indian rupees 8,000) makes the milk not potable for a week. But the farmers might use the milk earlier to reduce loss of money. So the milk that we drink from large pools in larger diaries might also contain unacceptable doses of antibiotics.



The House of Lords in Britain was worried about the large scale abuse of antibiotics in farming and spoke of a "vicious circle repeatedly witnessed in which the value of each new antibiotic has been progressively eroded by resistance." Very dangerous indeed. In a shocking incidence recently at the Prince Edward Hospital in Wales a patient had an infection in his leg wherein the germs were resistant to all the antibiotics available. Doctors had to go back to Nature to get maggots to help cure that infection! Now they are routinely culturing maggots to treat resistant infections there. In Nature this is a very common way of controlling bacterial infections, evident even during the Second World War.



Minor wounds could be smeared with fresh, clean honey. Honey gives a coating to the wound to prevent germs getting in and the germs already there are prevented from multiplying, as honey stops the nutrition needed for growth and multiplication in the germ world. Therefore the existing germs die out and the new ones can not get in.



The time bomb of tuberculosis is threatening to burst anytime now. The West is in the middle of the worst TB epidemic in the last twenty years. Tuberculosis never went away. It was only lying low because we depended on the powers of the anti-TB antibiotics too much and did away with the methods to enhance the capacity of the immune system as we used to do before the advent of antibiotics. Sanatoria, good food, complete rest, and a healthy environment were given up as useless. Surgery, which in the olden days, helped to get rid of the infected part of the lung, thereby reducing the risk of death and bleeding, took a back seat. Now we are threatened by the MDR, multiple drugs resistant germs of this deadly disease, waiting to produce another epidemic of the white death. Thomas Dormandy in his treatise The White Death (The Hambledon Press) gives us the horror stories of the hoary past with even people like Napoleon Bonaparte having suffered its ravages.



TB is no respecter of status or position and even money power for that matter. Many were the victims such as leaders, poets (Keats was the leading one), writers, soldiers, beggars, children, adults, mothers and also the medical and the nursing professionals. Many careers had to be either terminated or changed in mid-waters when TB struck. Things could be gloomier with the added burden of AIDS reducing the potency of the immune system of man. Vaccination against TB came and went without much fanfare. May be we need to look more carefully into this aspect of TB prevention.



This should alert all good Samaritans about the time bomb ticking away threatening to explode any time now. While I am sure the situation is worse in India, I have no scientific data for the whole country to give you the true picture. Earlier we wake up from our deep slumber the better for our progeny. We have never been using antibiotics scientifically for well over half a century in this country and the results could be disastrous to say the least.





Long Term Treatment with Drugs:





It is our duty to help patients in distress and those who have symptoms of diseases. Any drug, including antibiotics, will have to be given to relieve symptoms and many of them in short courses do not harm the system at all. Even then care must be taken to see that the minimum drugs are used with the right indications. When it comes to long term use almost all drugs are dangerous. There are many reasons for this. One of the most important reasons is that time evolution in any dynamic systems, like the human body, does not follow the linear rules. To give concrete example let us consider anti-hypertensive drugs. Most of them effectively lower the box blood pressure. If given in a healthy young man on a life long basis in the fond hope that it would keep the pressure down and do good to the patient, the results could be harmful. (Heart 1999; 82: 477-81) If the patient with hypertension has symptoms or has evidence of organ damage we have to take this risk in giving drugs on long term basis. In an otherwise healthy individual with just elevated blood pressure long term use of any drug has not been shown to be safe. It could even be harmful.( Lancet 1998; 352: 571) Long term audit did show that “well” controlled hypertensives have had two to three times higher mortality after the first five years, compared to their normotensive cousins in society. (BMJ 1998; 317: 167-71) To make matters worse, all the six international guidelines for treating high blood pressure cover just about 39% of the hypertensive population in their inclusion criteria. The rest will have to depend on their doctor’s wisdom!



Similar is the story of anti-diabetic drugs. While anti-diabetic drugs do very well in managing symptomatic diabetics, they might have, possibly, even harmed some healthy asymptomatic hyperglycaemics. (Diabet. Med 1999; 16: 23-30) Reanalysis of the (in) famous UKPDS study showed, if anything, more harm done than good to patients on oral anti-diabetic drugs. (BMJ 2000; 320: 1720-23)



Another class of drugs that might harm the system in the long run is the anti-inflammatory analgesics. (Arch.Int. Med 2000; 160: 777-84) Even an innocuous drug like paracetamol had killed one hundred thirty-six patients in one year in a small country like Britain. Painkillers are used with or without prescription in many countries and they cause the maximum drug induced damage.



Anti-cancer drugs have not acquitted themselves well either. Many of them harm the normal body cells as much, if not more, than the cancer cells. New drug delivery systems to target the drug to the cancer cells are in progress though.



Cholesterol lowering drugs is a big story. Starting with the first drug cholestyramine to the latest statins they have had their share of sorrow. While short term studies have shown many of them in good light, long term usage has been shown to have increased total mortality, despite the fact that they have marginally reduced the non-fatal myocardial infarctions. Many of the earlier drugs had in fact been quite harmful. Long term use of one of the latest statins, cervistatin, has shown to be dangerous to the muscles.



Anti-arrhythmic drugs are another similar story. The CAST study showed that almost all of them, starting from the old lignocaine to some of the recent ones, like encanide, have been arrhythmogenic in the long run. (J. Cardiovasc. Electrophysiol 1998; 9: 864-91)



Latest in this area has been the revelations about the much touted HRT (hormone replacement therapy) While it would be very useful for a few months or weeks in symptomatic post-menopausal women, HRT has been shown, in long term studies, to have increased the very diseases that they were supposed to reduce, viz. breast cancer, heart attacks and venous thrombo-embolism.





The bane of drug toxicity has been our irrational thinking in this area. We look at all these drugs with our tinted reductionist glasses. (Lancet 1998; 351: 1291) If a chemical does some good to a single cell in the laboratory we presume that it will do the same thing for the whole human body and prepare that chemical as a drug for use in man. Unfortunately, the body works as a whole. The chemical that seems to do good in a laboratory might not have the same effect in the body. Another problem is that if the drug has a particular effect at a given time inside the system, that good effect might not hold good as time evolves. Until we realize this fallacy and work in the direction of looking at the whole with the new science of fractals and chaos, we will be doing a lot of harm to patients. (BMJ 1991; 303: 1565-68) To begin with we could contain the harm by rational drug use, mostly on short-term basis, and avoid long term usage unless the situation definitely warrants it. If the benefit of giving a drug outweighs its dangers, then, and then only should the drug be administered on a long-term basis. Drug combinations, especially mixing many drugs together at the same time, could create another dangerous situation of drug interactions with disastrous consequences. In addition, close monitoring is essential in all long term drug users, irrespective of the drug.



Should doctors be therapeutic nihilists? The answer is an emphatic no. However, the irrational use of drugs has landed us in a very bad patch. Time is running out. We should alert the medical profession of the tricks of the trade of the drug companies to sell their drugs to the gullible public, using the trust the patients place in the medical profession. We have a moral responsibility to the public to guard against this kind of agenda of the drug companies. Pharmaceutical industry has even been found to have bribed doctors and the powers-that-be to get their drugs pushed. The American Heart Association’s guidelines committee’s recommending tissue plasminogen activator following stroke had coincided with the company paying eleven million dollars to the association. The American medical education itself has been found to be dependent on drug company money! Academic medicine seems to be on sale. (NEJM 2000; 342: 1516-17) If one looks at the gift horse of the industry in the face, one would be shocked to see the skeletons in their cupboards. (JAMA 1998; 279: 995-999)



The vital action that the medical profession has to take would be to be pro-active to bring in some degree of awareness among the doctors of all the details mentioned earlier to see that they do not resort to irrational drug use. Unfortunately, this kind of information rarely reaches the practising doctors. They depend on the medical representatives of the drug companies to get their much-needed post-graduate education. Most, if not all of it, would only be the company’s propaganda literature. We teachers have a great responsibility on our shoulders to not only guide the students in the college but to see that the practising doctors get the right kind of continuing professional development.