Medicine for People!

June 2004

Contents

• 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 genieout of a bottle, only in this case you're letting the genie into yourprecious, complex body. The genie can save your life with its mightymagic. It can also get into mischief or do unexpected good. Theseunintended 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 forstrep throat. The intended effect is to wipe out harmful bacteria. If thedrug makes you nauseous, that is a side effect. The drug is just mindingits own business and you react in two ways - one intended and beneficial,the other unintended and unwelcome. We give erythromycin to end aninfection, so if it upsets the stomach, we aren't happy about that.

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

Please note that side effects are not the same thing as allergies. When theimmune 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 asswelling in the throat or the lungs. A side effect is quite different froman allergy, because the immune system is not involved.

Determining Side Effects

Our knowledge of side effects is still a work-in-progress. In the earlygroup of men given sildenafil (Viagra(R)), a few dropped dead of heartattacks. (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 ayear, and six per thousand in men who didn't. The apparent side effect ofsudden cardiac death from sildenafil turned out to be an illusion. On theother hand, some side effects are quite real but only touch a fewindividuals. Perhaps every other day a person comes into my office with anunexpected effect from a drug, a side effect that is not listed in thetextbooks. 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, anotherantibiotic, is a case in point. Azithromycin has the unintended effect ofdilating the bronchial tubes. If you take it for bronchitis, you'llbreathe more easily. You won't breathe more easily because it killed thevirus causing the bronchitis. Azithomycin doesn't kill viruses. Butyou'll feel better. You, and even the health care provider who gave it toyou, may be fooled into thinking it is curing you. Better, however, totreat the bronchospasm directly with an albuterol (asthma) inhaler orcortisol and save azithromycin for the day you really need it to kill badbugs. 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 pu rpose and, because of itsbeneficial side effects, end up being used for another. Take the exampleof amitriptylene. This was the original antidepressant, effective at dosesof 200 to 300 milligrams per day. There was just one little problem -- noone could stay awake on that dose. People who took it were relieved oftheir depression, but they ended up snoring in their soup. Amitriptylenewas 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 orless. It is inexpensive and, unlike other sleeping pills, doesn't resultin habituation. It is also an effective pain reliever, especially inpeople with pain from the nerves in the neck or back. So amitriptylene isnow used for what were originally considered side effects.

Serious Side Effects

An antibiotic called chloramphenicol was popular in the 1970's. It is agreat antibiotic, but occasionally hammers the bone marrow, resulting indeath. Garamycin is another antibiotic, very effective and necessary incertain 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. Theseare serious side effects. No decent US physician gives you a drug likethis without a good reason. If they do prescribe one of thse 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 ofrelatively 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 prominentblack box. With thousands of pharmaceuticals and up to a hundred or moreside effects for each one, we physicians need those black boxes.Frequently, even though we in general practice know pretty much what thespecialist will use for that rheumatoid arthritis, we let him or herprescribe and manage it. They know better how to use these potentiallydangerous drugs.

Misleading labels

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

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

Second, for some drugs, side effects associated with high doses virtuallynever crop up with a low dose. For example, we prescribe low-dose cortisolfor many patients. The pharmacy computers spit out all the terrible sideeffects for high-dose synthetic cortisol-like drugs. None of these sideeffects apply to low-dose cortisol. The computer list only serves to scarethe dandruff off my patients.

Dose Level and Side Effects

Almost any drug will have side effects when given at high doses. In thecase of the hormones testosterone or estrogen, the side effects canactually be a guide allowing us to adjust the dose to your particularrequirements. Our bodies require a certain amount of all hormones, be theycortisol, thyroid, estrogen or testosterone. If our levels are low, wesuffer consequences, such as the hot flashes that come when estrogen levelsdrop. 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 wefind 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. Inst ead,researchers give a wide range of doses to a lot of people. Then they recordhow many people experienced relief at each dose, and how many experiencedside effects. They pick a dose that maximizes benefits and minimizes sideeffects for the AVERAGE person. For example, the common pain-relieveribuprofen (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 gastrointestinalupset, varying degrees of pain and inflammation, and varying levels ofcytochrome 2C9, an enzyme in the liver that clears ibuprofen from thesystem. We'll tell you more about cytochrome 2C9 in next month'snewsletter. Emerging knowledge of such enzymes is soon going to change theway we use medication and help us understand why drugs cause adverseeffects in some people but not others.

Occasional vs. Regular Use

Regular use of a drug may cause side effects that seldom appear withone-time or occasional use. Propranolol, an adrenaline blocker, can causesymptoms of depression when taken daily for a long time. However, manypeople with depression have occasional short bouts of anxiety. Taking asmall dose of propranolol at that time can totally squelch those jittersand shaky hands. Many concert soloists use propranolol before aperformance to eliminate stage fright. Eye surgeons know that the hand thatlooks steady to the unaided eye actually can be quite shaky when viewedthrough an operating microscope. Many surgeons using microscopictechniques take a dose before operating to steady their hand. Thesurgeon's judgment and alertness are not affected, and the operationproceeds more smoothly. Despite the warning from the pharmacy computer, anoccasional 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 severaldrugs. He was put off by the side effects, and no argument would win himover... 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 hewas 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 thesefits 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, andunexpected consequences.

Dealing With Side Effects

Many minor side effects will disappear with the passage of a few days orwith a reduction in the dose. Read the information on the bottle and takeit 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 thepast 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 canbe quite neighborly if you take it with food. Taking the drug correctlygoes a long way towards eliminating side effects.

Sometimes side effects are just going to happen. Maybe you have to take atoxic 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'sthe truth. This substance may temporarily make you sick but may also saveyour life.

Most drugs used in a general practice office such as mine are more likelyto help you than to cause side effects. Like other caring physicians, I domy best to fine-tune dosage and adjust medications to eliminate sideeffects. However, sometimes side effects can't be avoided. My experienceis that my patients who view the medication as a positive thing, a boon, ahealing gift, have less distress from side-effects and enjoy a betterresult from treatment. There is nothing "woo-woo" about this. When wefind a way to accept the suffering life brings, or the possibility ofsuffering, our anxiety is less. We bear the suffering better, ourphysiologic systems operate more effectively with fewer stress hormones inour 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 waspulled off the market. Fenfluramine was a good drug for people who tendedto gain and hold on to excess weight. Given with phentermine (the fen-phencombination), results were even better. Many of my patients who tookfenfluramine said they felt normal for the first time in years. They didn'tfeel driven to eat; they could think better and felt happier. Fenfluramineincreases dopamine levels in the brain. Dopamine levels fall as peoplegain weight. When dopamine is low, we do not feel good. So an overweightperson can reach the point where the only way to increase dopamine levelsand 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 wentoff the market, a funny thing happened. When fen-phen was stopped, theheart damage often regressed.

The New England Journal (August 1996; 335:609) reported that the mostserious complication of fenfluramine, high blood pressure affecting thelungs, while fatal half the time, occurred in only about 28 people permillion, for each year the drug is taken. However, obesity is also akiller. An estimated 280 people a year would have their lives saved bylosing weight. Compare 14 deaths per million per year from the drug to 280deaths without the drug. Thickening of the heart valves occurred in 5 to10 percent of patients and usually improved or remained stable when thefen-phen was discontinued.

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

Monroe Street Medical Clinic News - Free Advice

If you have a minor problem that you do not think requires Dr Rienstra'sattention, but you would like to know what we might do about it, ask ourreceptionist about our Free Advice.

Medicine for People! is published by Douwe Rienstra, MD at Port Townsend, Washington. Edited by Carolyn Latteier.

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