Drugs and Their Side-Effects, Phen-fen: Good Drug or Bad?

• Drugs and Their Side Effects
• Determining Side Effects
• Beneficial Side Effects
• Serious Side Effects
• Misleading Labels
• Occasional Vs Regular Use
• Accepting Side Effects
• Dealing With Side Effects
• Rant 'O The Month - Fen-Phen, Good Drug or Bad?
• Monroe Street Medical Clinic News - Free Advice

Drugs and Their Side Effects

Taking a prescription pharmaceutical is a little bit like letting a genie out of a bottle, only in this case you're letting the genie into your precious, complex body. The genie can save your life with its mighty magic. It can also get into mischief or do unexpected good. These unintended consequences we call side effects.

A side effect is a secondary and usually adverse result from taking a drug. Say, for instance, your doctor prescribes the antibiotic erythromycin for strep throat. The intended effect is to wipe out harmful bacteria. If the drug makes you nauseous, that is a side effect. The drug is just minding its own business and you react in two ways - one intended and beneficial, the other unintended and unwelcome. We give erythromycin to end an infection, so if it upsets the stomach, we aren't happy about that.

If, however, we had intended to upset your stomach, it would not be considered a side effect. For example, we give ipecac to make a person vomit up poison. If you take ipecac, get nauseated and throw up, we don't call it a side effect. We call it success.

Please note that side effects are not the same thing as allergies. When the immune system overreacts to a foreign substance, we call that an allergy. An allergy may be as innocuous as a little rash or as life threatening as swelling in the throat or the lungs. A side effect is quite different from an allergy, because the immune system is not involved.

Determining Side Effects

Our knowledge of side effects is still a work-in-progress. In the early group of men given sildenafil (Viagra(R)), a few dropped dead of heart attacks. (Wags commented that at least they died happily.) At that time,we routinely told men that cardiac arrest was a possible side effect. (None of my patients paused more than a heartbeat before saying "That's OK,just write the prescription.") Later surveillance found that on average,the heart attack rate was four per thousand men who took sildenafil for a year, and six per thousand in men who didn't. The apparent side effect of sudden cardiac death from sildenafil turned out to be an illusion. On the other hand, some side effects are quite real but only touch a few individuals. Perhaps every other day a person comes into my office with an unexpected effect from a drug, a side effect that is not listed in the textbooks. Sometimes a symptom is too vague or too unusual to make it onto the list.

Beneficial Side Effects

Sometimes we like the side effects of a drug. Azithromycin, another antibiotic, is a case in point. Azithromycin has the unintended effect of dilating the bronchial tubes. If you take it for bronchitis, you'll breathe more easily. You won't breathe more easily because it killed the virus causing the bronchitis. Azithomycin doesn't kill viruses. But you'll feel better. You, and even the health care provider who gave it to you, may be fooled into thinking it is curing you. Better, however, to treat the bronchospasm directly with an albuterol (asthma) inhaler or cortisol and save azithromycin for the day you really need it to kill bad bugs. Azithromycin should never be used intentionally as a bronchodilator. It is much too valuable an antibiotic to waste in such a fashion.

Sometimes a drug will be developed for one purpose and, because of its beneficial side effects, end up being used for another. Take the example of amitriptylene. This was the original antidepressant, effective at doses of 200 to 300 milligrams per day. There was just one little problem -- no one could stay awake on that dose. People who took it were relieved of their depression, but they ended up snoring in their soup. Amitriptylene was quickly replaced by other antidepressants that did not knock people out.

Guess what we use amitriptylene for now? That's right - insomnia. Amitriptylene is very good for inducing sleep in doses of 100 milligrams or less. It is inexpensive and, unlike other sleeping pills, doesn't result in habituation. It is also an effective pain reliever, especially in people with pain from the nerves in the neck or back. So amitriptylene is now used for what were originally considered side effects.

Serious Side Effects

An antibiotic called chloramphenicol was popular in the 1970's. It is a great antibiotic, but occasionally hammers the bone marrow, resulting in death. Garamycin is another antibiotic, very effective and necessary in certain situations, but too much of the drug causes permanent deafness. Coumadin and the 'clot-busting" cardiac drugs can cause fatal bleeding; digitalis can cause fatal heart arrhythmias, and the list goes on. These are serious side effects. No decent US physician gives you a drug like this without a good reason. If they do prescribe one of these medicines, they will inform you of these serious side effects and make every effort, including monitoring blood levels, to avoid them.

For every drug, the reference books on pharmaceuticals have a long list of relatively minor side effects -- like headache, diarrhea, and so forth --that won't kill you and that go away once you stop the drug. Serious, potentially fatal side effects are often highlighted inside a prominent black box. With thousands of pharmaceuticals and up to a hundred or more side effects for each one, we physicians need those black boxes. Frequently, even though we in general practice know pretty much what the specialist will use for that rheumatoid arthritis, we let him or her prescribe and manage it. They know better how to use these potentially dangerous drugs.

Misleading labels

Today, pharmacy computers will spit out side-effect profiles for every drug you buy. While this is an advance over the dark ages when you never knew what to expect, it has its own pitfalls.

First, the lists are too long. These side-effect profiles go on and on about nausea, diarrhea, headaches and such. The truth is most drugs will cause nausea and diarrhea in at least a few people. Unfortunately, the long lists of minor side effects may confuse people and deflect them from more important concerns.

Second, for some drugs, side effects associated with high doses virtually never crop up with a low dose. For example, we prescribe low-dose cortisol for many patients. The pharmacy computers spit out all the terrible side effects for high-dose synthetic cortisol-like drugs. None of these side effects apply to low-dose cortisol. The computer list only serves to scare the dandruff off my patients.

Dose Level and Side Effects

Almost any drug will have side effects when given at high doses. In the case of the hormones testosterone or estrogen, the side effects can actually be a guide allowing us to adjust the dose to your particular requirements. Our bodies require a certain amount of all hormones, be they cortisol, thyroid, estrogen or testosterone. If our levels are low, we suffer consequences, such as the hot flashes that come when estrogen levels drop. If our levels are normal, we feel normal. If our levels are high, we suffer symptoms, such as sore breasts in the case of estrogen. When we find the dose that quells the hot flashes without causing sore breasts, then we've got it right.

Drug doses do not come down from heaven on a granite tablet. Instead, researchers give a wide range of doses to a lot of people. Then they record how many people experienced relief at each dose, and how many experienced side effects. They pick a dose that maximizes benefits and minimizes side effects for the AVERAGE person. For example, the common pain-reliever ibuprofen (Motrin) is FDA approved at doses between 200 and 3200 milligramsa day. The reason for the wide dose range is that people are different. (What a concept!) People have varying tolerances for the gastrointestinal upset, varying degrees of pain and inflammation, and varying levels of cytochrome 2C9, an enzyme in the liver that clears ibuprofen from the system. We'll tell you more about cytochrome 2C9 in next month's newsletter. Emerging knowledge of such enzymes is soon going to change the way we use medication and help us understand why drugs cause adverse effects in some people but not others.

Occasional vs. Regular Use

Regular use of a drug may cause side effects that seldom appear with one-time or occasional use. Propranolol, an adrenaline blocker, can cause symptoms of depression when taken daily for a long time. However, many people with depression have occasional short bouts of anxiety. Taking a small dose of propranolol at that time can totally squelch those jitters and shaky hands. Many concert soloists use propranolol before a performance to eliminate stage fright. Eye surgeons know that the hand that looks steady to the unaided eye actually can be quite shaky when viewed through an operating microscope. Many surgeons using microscopic techniques take a dose before operating to steady their hand. The surgeon's judgment and alertness are not affected, and the operation proceeds more smoothly. Despite the warning from the pharmacy computer, an occasional dose of propranolol won't cause or worsen depression.

Accepting Side Effects

Recently one of my patients with severe arthritis kept going downhill. There was no natural remedy that could help him, so I suggested several drugs. He was put off by the side effects, and no argument would win him over... until he became bed-ridden at home. When I called at his house, his wife put her foot down. Onto the drugs he went, and the next day he was out of bed. Sure enough, a few days later he developed some diarrhea,and we had to change his medication to eliminate that. However, with these fits and starts, he is feeling better.

The moral of this story is that sometimes the side effects are worth it. The road to better health, like any other road, can have twists, turns, and unexpected consequences.

Dealing With Side Effects

Many minor side effects will disappear with the passage of a few days or with a reduction in the dose. Read the information on the bottle and take it as directed. Some drugs are best taken with meals, others at bedtime. For instance, erythromycin is an effective antibiotic in many situations,and much less expensive than the newer antibiotics. If you've found in the past it upset your stomach, then take it with meals and it often won't. Erythromycin is like aspirin, which may upset your empty stomach, but can be quite neighborly if you take it with food. Taking the drug correctly goes a long way towards eliminating side effects.

Sometimes side effects are just going to happen. Maybe you have to take a toxic medication to improve your chances of surviving cancer. Frankly, some of the side effects are unpleasant. I ask you look at the medication, depending on your beliefs, as a gift of God or Nature. I believe that's the truth. This substance may temporarily make you sick but may also save your life.

Most drugs used in a general practice office such as mine are more likely to help you than to cause side effects. Like other caring physicians, I do my best to fine-tune dosage and adjust medications to eliminate side effects. However, sometimes side effects can't be avoided. My experience is that my patients who view the medication as a positive thing, a boon, a healing gift, have less distress from side-effects and enjoy a better result from treatment. There is nothing "woo-woo" about this. When we find a way to accept the suffering life brings, or the possibility of suffering, our anxiety is less. We bear the suffering better, our physiologic systems operate more effectively with fewer stress hormones in our system, and we are more likely to return to good health.

Rant O' The Month: Fen-phen, Good Drug or Bad?

A couple of years ago, the popular weight loss combination fen-phen was pulled off the market. Fenfluramine was a good drug for people who tended to gain and hold on to excess weight. Given with phentermine (the fen-phencombination), results were even better. Many of my patients who took fenfluramine said they felt normal for the first time in years. They didn't feel driven to eat; they could think better and felt happier. Fenfluramine increases dopamine levels in the brain. Dopamine levels fall as people gain weight. When dopamine is low, we do not feel good. So an overweight person can reach the point where the only way to increase dopamine levels and feel normal is to eat. Fen-phen helped alleviate that syndrome.

Then fen-phen was found to cause heart damage in some users. After it went off the market, a funny thing happened. When fen-phen was stopped, the heart damage often regressed.

The New England Journal (August 1996; 335:609) reported that the most serious complication of fenfluramine, high blood pressure affecting the lungs, while fatal half the time, occurred in only about 28 people permillion, for each year the drug is taken. However, obesity is also a killer. An estimated 280 people a year would have their lives saved by losing weight. Compare 14 deaths per million per year from the drug to 280 deaths without the drug. Thickening of the heart valves occurred in 5 to 10 percent of patients and usually improved or remained stable when the fen-phen was discontinued.

Should fenfluramine return to the market? It has some serious side effects, but so do many other drugs we use for grave illness. With continued use, we should be able to monitor for and prevent some of the adverse effects. If I were obese, I'd like to have that choice.

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