Drug-Induced Diseases

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Drug-Induced Diseases http://worstpills.org/public/page.cfm?op_id=5 How Extensive Is the Problem of Specific Adverse Drug Reactions?Each year, more than 9.6 million adverse drug reactions occur in older Americans. The referenced study found that 37% of these adverse reactions were not reported to the doctor, presumably because patients did not realize the reactions were due to the drug. This is not too surprising considering that most doctors admitted they did not explain possible adverse effects to their patients.1 The following national estimates are based on well-conducted studies, mainly in the United States:Each year, in hospitals alone, there are 28,000 cases of life-threatening heart toxicity from adverse reactions to digoxin, the most commonly used form of digitalis in older adults.2 Since as many as 40% or more of these people are using this drug unnecessarily (see discussion on digoxin), many of these injuries are preventable.Each year 41,000 older adults are hospitalized—and 3,300 of these die from ulcers caused by NSAIDs (nonsteroidal anti-inflammatory drugs, usually for treatment of arthritis).3 Thousands of younger adults are hospitalized. (See list of drugs that can cause gastrointestinal bleeding.)At least 16,000 injuries from auto crashes each year involving older drivers are attributable to the use of psychoactive drugs, specifically benzodiazepines and tricyclic antidepressants.4 Psychoactive drugs are those that affect the mind or behavior. (See list of drugs that can cause automobile accidents.)Each year 32,000 older adults suffer from hip fractures—contributing to more than 1,500 deaths—attributable to drug-induced falls.5 6 In one study, the main categories of drugs responsible for the falls leading to hip fractures were sleeping pills and minor tranquilizers (30%), antipsychotic drugs (52%), and antidepressants (17%). All of these categories of drugs are often prescribed unnecessarily, especially in older adults. (See section on sleeping pills and tranquilizers, antipsychotic drugs, and antidepressants.) The in-hospital death rate for hip fractures in older adults is 4.9%.7 Multiplying this times the 32,000 hip fractures a year in older adults attributable to drug-induced falls, 1,568 older adults die each year from adverse drug reactions that cause hip fractures. (See list of drugs that can cause hip fractures because of drug-induced falls)Approximately 163,000 older Americans suffer from serious mental impairment (memory loss, dementia) either caused or worsened by drugs.8 9 In a study in the state of Washington, in 46% of the patients with drug-induced mental impairment, the problem was caused by minor tranquilizers or sleeping pills; in 14%, by high blood pressure drugs; and in 11%, by antipsychotic drugs. (See list of drugs that can cause or worsen dementia.)Two million older Americans are addicted or at risk of addiction to minor tranquilizers or sleeping pills because they have used them daily for at least one year, even though there is no acceptable evidence that the tranquilizers are effective for more than four months, and the sleeping pills for more than 30 days.10 Drug-induced tardive dyskinesia has developed in 73,000 older adults; this condition is the most serious and common adverse reaction to antipsychotic drugs, and it is often irreversible. Tardive dyskinesia is characterized by involuntary movements of the lips, tongue, and sometimes the fingers, toes, and trunk. Since most of the older people taking these drugs were not actually psychotic, they have a serious side effect from antipsychotic drugs prescribed without justification.11 (See list of drugs that can cause tardive dyskinesia or other movement disorders.)Drug-induced parkinsonism has developed in 61,000 older adults due to the use of antipsychotic drugs such as Haldol, Thorazine, Mellaril, Stelazine, and Prolixin. There are also other parkinsonism-inducing drugs, such as Reglan, Compazine, and Phenergan, prescribed for gastrointestinal problems.12 As mentioned above, most (about 80%) older adults receiving antipsychotic drugs do not have schizophrenia or other conditions that justify the use of such powerful drugs. (See list of drugs that can cause parkinsonism.)A serious problem exists because both doctors and patients do not realize that practically any symptom in older adults and in many younger adults can be caused or worsened by drugs.13 13 Some doctors and patients assume that what are actually adverse drug reactions are simply signs of aging. As a result, many serious adverse reactions are entirely overlooked or not recognized until they have caused significant harm.The drugs responsible for the most serious adverse reactions in older adults are tranquilizers, sleeping pills, and other mind-affecting drugs; cardiovascular drugs such as high blood pressure drugs, digoxin, and drugs for abnormal heart rhythms;14 and drugs for treating intestinal problems.Mental Adverse Drug Reactions: depression, hallucinations, confusion, delirium, memory loss, impaired thinkingNervous System Adverse Drug Reactions: parkinsonism, involuntary movements of the face, arms, legs (tardive dyskinesia), sexual dysfunctionDizziness on Standing, Falls Sometimes Resulting in Hip Fractyures, Automobile Accidents Resulting in InjuryGastrointestinal Adverse Drug Reactions: loss of appetite, constipationUrinary Problems: difficulty urinating, leaking of urineSpecific Patient Examples of Drug-Induced DiseasesFifty-four-Year-Old Woman Homebound from Lung Toxicity due to a Heart Drug Never Approved to Treat Her ConditionLiz was prescribed the drug Cordarone to treat a common heart condition. She was not told that the drug was not approved by the FDA for her condition. The pharmacy leaflet mentioned nausea and dizziness with the drug, but not death from lung toxicity. She is now dependent on an oxygen tank to breathe and does not have the strength to clean her house. It is estimated that as many as 17% of patients experience lung toxicity from amiodarone, and about 10% of them die.Fifty-eight-Year-Old Man Develops Parkinsonism from Antipsychotic Drug Being Used to Treat His “Irritable Bowel” ProblemLarry, an otherwise healthy 58-year-old man with diarrhea believed to be due to “irritable bowel syndrome,” was given Stelazine, a powerful antipsychotic tranquilizer to “calm down” his intestinal tract. Stelazine is not even approved for treating such medical problems. Six months after starting Stelazine, Larry developed severe parkinsonism and was started on L-dopa, a drug for treating Parkinson’s disease. Presumably, the doctor did not realize the parkinsonism was drug-induced, and the Stelazine was continued. For seven years, Larry took both drugs. Then a neurologist specializing in Parkinson’s disease saw Larry, recognized the real cause of his problem, stopped the Stelazine, and slowly withdrew the L-dopa over a six-month period. Larry’s severe, disabling parkinsonism cleared completely.As mentioned above, 61,000 older adults develop drug-induced parkinsonism each year. At least 80% of them, like Larry, should never have been put on the drugs causing the parkinsonism in the first place. Also, as in Larry’s situation, a large proportion of these people have doctors who think that their parkinsonism developed spontaneously.The doctors not only fail to suspect that it is caused by a drug such as Stelazine, or other antipsychotic drugs (Reglan, Compazine, or Phenergan), but they add a second drug to treat the disease that has been caused by the first drug.The same neurologist who “cured” Larry of his drug-induced parkinsonism saw, in just three years, 38 other patients with drug-induced parkinsonism and 28 with drug-induced tardive dyskinesia.None of these people were psychotic, the one justification for antipsychotic medications. Rather, the most common reasons for using the parkinsonism-inducing drugs were chronic anxiety and gastrointestinal complaints. The most frequent culprit (in 19 of these 39 patients) was metoclopramide (REGLAN), usually prescribed for heartburn, or for nausea and vomiting. Doctors often prescribe Reglan before trying other more conservative and safer methods. Other drugs that brought on parkinsonism included Compazine, Haldol, and Thorazine.15 Sarah’s 80-Year-Old Father’s Confusion and Hallucinations Were Induced by His Ulcer DrugsSarah wrote us about her father, saying that she had to repeatedly nag his doctor about the possible role of her dad’s ulcer drugs in causing confusion and hallucinations before the doctor listened. Three different drugs—Tagamet, Zantac, and Pepcid—had been tried for her father’s ulcers, and each had caused these adverse reactions. When the doctor finally switched Sarah’s father to an antacid, Maalox, his mind completely cleared and he was his old self, no longer confused or hallucinating.Seventy-nine-Year-Old Woman Has Reversible Mental ImpairmentSally, the mother-in-law of a physician, was noted by her son-in-law, who had not seen her for several months, to have suffered severe impairment of her otherwise sharp mind. She was acting confused and, for the first time in her life, was unable to balance her checkbook. When questioned by her son-in-law, she was able to remember that her problem had started around the time she was put on a tranquilizer, Ativan. After this link was discovered, the drug was slowly discontinued and all of the mental impairment that had begun when the drug was started disappeared.Sixty-four-Year-Old Man Has Auto Accident After One Dose of TranquilizerBen, the 64-year-old uncle of a physician, was scheduled to have a biopsy done at a local hospital at eight in the morning. So that he would be relaxed for the biopsy, four days before it was to be done the doctor gave him a free sample of a tranquilizer, Xanax, to take an hour or so before the procedure. Ben was not told that he should not use drugs like this if he was going to drive and, while driving to the hospital for the biopsy, he blacked out. The car went over a fence and sustained $6,000 worth of damage, but fortunately Ben was unhurt. (See drugs that can cause automobile accidents.)Sixty-three-Year-Old Gets into “Drug-Illness” CycleNancy, a healthy 63-year-old woman, complained about difficulty going to sleep. Instead of taking a careful history and finding out that she had recently started drinking several cups of coffee at dinner, her doctor prescribed a sleeping pill. A subsequent referral was also made to a psychiatrist because of depression (possibly partly induced by the sleeping pill), and an antidepressant drug was also prescribed. If this patient also took an antihistamine-containing drug for a cold (not an effective treatment), she would be using three drugs, all of which have powerful sedative effects, which could make her so groggy that standing would be difficult, and falling would be easy.Sixty-Year-Old Woman Given “Overdose” of PropranololElsie, a 60-year-old woman who worked as an assistant at a senior citizens’ center, was started on propranolol to treat her high blood pressure. Unfortunately, her doctor did not realize that the dose of this sometimes useful drug (see propranolol (INDERAL, INDERAL LA)) must be reduced in older adults, and she was prescribed 80 milligrams twice a day. Two days after she started taking the drug, she began feeling very weak—so much so that by the third day, she went to a hospital emergency room, where her pulse rate was found to be 36 beats per minute. This dangerously low rate fully explained her weakness. The drug was stopped and Elsie’s heart rate returned to normal. Later a low dose of a different drug was prescribed and had no adverse effects.Seven-Year-Old Boy Dies from Drug Prescribed for Attention Deficit Hyperactivity DisorderBernie, a bright 7-year-old, was prescribed an antidepressant, imipramine (TOFRANIL), to treat attention deficit hyperactivity disorder. Because his parents were not provided with accurate, complete information about the drug, they were unaware that the drug could cause life-threatening heart arrhythmias, that the dose prescribed was too high, and that the tremor and convulsions that Bernie began to have were actually adverse drug reactions to imipramine. Treatment with the drug was continued, and one day, while at school, he collapsed and died of a heart arrhythmia. If his parents had been adequately warned about this drug, Bernie would be alive today.In discussing the problem of adverse drug reactions in the elderly, the World Health Organization has stated some principles applicable to people of all ages: “Quite often, the history and clinical examination of patients with side effects reveal that no valid indication [purpose] for the offending drug has been present...Adverse reactions can to a large extent be avoided in the elderly by choosing safe and effective drugs and applying sound therapeutic principles in prescribing, such as starting with a small dose, observing the patient frequently, and avoiding excessive polypharmacy [the use of multiple drugs at the same time].”16 In other words, according to the World Health Organization, patients who suffer adverse drug reactions are very often victims of drugs that there is no valid reason for them to take.A carefully controlled study examined the details of prescriptions of people being discharged from a community hospital with three or more prescriptions to treat chronic illnesses.17 The results of this study are quite disturbing, both in what they say about the doctors’ prescribing practices and in the evidence as to the potential damage that could be done to older adults as a result of these practices. Of the 236 people intensively studied:Eighty-eight percent of the people had one or more prescribing problems with the prescriptions they were given. At least one potentially serious, life-threatening problem occurred, which could have been as a result of the prescriptions written for 22% of these patients.When the specific problems with the prescriptions were examined, the results were as follows:Fifty-nine percent of the patients had been given one or more prescriptions for a drug that was an inappropriate choice of therapy because it was either “less than optimal medication given the patient’s diagnosis” or there was no established indication for it;Twenty-eight percent of the patients were given too high a dose of the drug, an “overdose”;Forty-eight percent of the patients were given a combination of drugs that can result in one or more harmful drug interactions;Twenty percent of the patients were given drugs that unnecessarily duplicated the therapeutic effect of another drug they were taking.The good news from this study, however, was that a consultant pharmacist, involved in the care of more than 50% of these patients, was able to reduce the risks by making recommendations to the prescribing physicians.Available on the web site are lists of the most common drug-induced adverse effects along with the drugs that can cause them. In the box below are some of the symptoms that, although they are frequently caused by drugs, are the kinds of problems that you or many doctors might first attribute simply to “growing old” or “getting nervous” instead of to a drug.Which Adverse Effects Can Be Caused by Which Drugs?The drug-induced disease lists on this web site are to be used by patients who have any of a variety of medical problems (or by doctors) to find out which drugs, especially ones they are using or are considering using, can cause specific adverse reactions. The lists are compiled from a variety of sources.18 19 20 21 22 23 24 Although some of these adverse effects occur most commonly in older adults, all of them have also been documented in younger people, although not as often in some instances.SUMMARY OF ADVERSE REACTIONS AND THE DRUGS THAT CAUSE THEMOnly the most easily detectable problems are considered, and only the most common drugs causing each problem are listed.Adverse Drug ReactionNumber of DrugsExamples of Brand NamesDepression166Accutane, Advil, Catapres, Cipro, Dalmane, Factive, Inderal, Naprosyn, Norpace, Pepcid, Reglan, Tagamet, Talwin, Ultracet, Valium, Xanax, ZantacPsychoses/ hallucinations156Aldomet, Benadryl, Catapres, Celebrex, Cipro, Dexatrim, Elavil, Halcion, Inderal, Lanoxin, Procanbid, Sonata, Tagamet, Ultracet, Valium, VioxxConfusion/ delirium147Amaryl, Ambien, Benadryl, Catapres, Cipro, Compazine, Diabeta, Diabinese, Dymelor, Elavil, Mellaril, Sinemet, Tagamet, Valium, Xanax, ZantacDementia76Aldomet, Inderal, Maxzide, Mellaril, Regroton, Restoril, Ser-Ap-Es, Tagamet, Valium, Xanax,ZantacInsomnia35Avelox, Floxin, Inderal, Lasix, Mevacor, Nicorette, Sudafed, Synthroid, Theo-24Parkinsonism40Abilify, Aldomet, Asendin, Cardizem, Compazine, Elavil, Geodon, Haldol, Mellaril, Prozac, Reglan, Regroton, Risperdal, ThorazineTardive dyskinesia19Abilify, Asendin, Buspar, Compazine, Geodon, Haldol, Mellaril, Risperdal, Thorazine, Wellbutrin, Zyban, ZyprexaDizziness on standing154Abilify, Calan SR, Cardizem CD, Cardura, Catapres, Compazine, Elavil, Geodon, Haldol, Hytrin, Inderal, Isordil, Lasix, Minipress, Nitro-Bid, Prinivil, Procardia, Sonata, Tenormin, Valium, XanaxFalls/hip fracture59Ambien, Celexa, Compazine, Dalmane, Elavil, Haldol, Isordil, Lexapro, Navane, Nembutal, Prozac, Restoril, Sinequan, Valium, XanaxAutomobile accidents28Ambien, Asendin, Ativan, Celexa, Elavil, Lexapro, Norpramin, Pamelor, Paxil, Prozac, Sinequan, Tofranil, Valium, Xanax, ZoloftSexual dysfunction127Abilify, Calan SR, Geodon, Lopid, Lopressor, Norpace, Pepcid, Proscar, Prozac, Sarafem, Tagamet, Tegretol, Transderm-Scop, ZantacLoss of appetite, nausea, vomiting63Advil, Avelox, Daypro, Demerol, EES, Feldene, Feosol, K-Lor, Lanoxin, Levaquin, Relafen, Sumycin, Theo-24, Ultracet, UltramAbdominal pain, ulcers, GI bleeding48Advil, Anaprox, Celebrex, Cortone, Daypro, Decadron, Feldene, Indocin, Motrin, Relafen, Somophyllin, Theo-24, Ultracet, Vioxx, ZithromaxConstipation107Amphojel, Benadryl, Caltrate, Cogentin, Inderal, Lotronex, Maalox, Talwin, Tylenol No. 3, Tylox, Ultram, UrisedDiarrhea56Aciphex, Aldomet, Avelox, Cipro, Dulcolax, Maalox, Phillips’ Milk of Magnesia, Nexium, Peri-Colace, Precose, Prilosec, Sporanox, Sumycin, ZelnormLung toxicity59Cordarone, Feldene, Inderal, Prinivil, Tegretol, Vasotec, ViskenBlocked urination56Antivert, Artane, Benadryl, Bentyl, Compazine, Duragesic, Elavil, Felbatol, Haldol, Sinequan, Tavist, Ultram, ZybanUrine leakage84Aricept, Celexa, Esidrix, Hytrin, Inderal, Lasix, Lexapro, Lithobid, Minipress, Neurontin, Paxil, Restoril, Tenormin, Valium, Xanax, Zaroxolyn, Ziac, Zoloft1 Of the 42.34 million Americans 60 and older (Statistical Abstracts of the United States 1992, 1991 population data) approximately 90% are taking one or more medications for a total of 37.83 million older people. According to a study of verified adverse drug reactions (German PS, Klein LE. Adverse drug experience among the elderly. Pharmaceuticals for the Elderly. Pharmaceutical Manufacturers Association, November 1986), 25.4% of the elderly patients 60 and older had at least one adverse drug reaction during the six-month interval that the study encompassed. Twenty-five and four-tenths percent of 37.83 million people is 9.61 million adverse reactions for the six-month period. The number of adverse reactions in a year would certainly be higher. The actual number of adverse reactions is also much higher since this calculation assumes all patients were being seen outside of the hospital or nursing home. Because the use of drugs in nursing homes and hospitals is much higher than in clinics, the number of adverse reactions is also higher. 2 Using the basis for estimating the number of admissions to medical wards of hospitals of 6.05 million in 1990 (see reference 1 in the previous chapter for the basis of this estimate), and the estimate that in 22.4% of medical admissions the patients are using digoxin and that 2.06% of these suffer life threatening heart toxicity from digoxin (both are from Miller RR, Greenblatt DJ. Drug Effects in Hospitalized Patients. New York: John Wiley and Sons, 1976), this amounts to 6.05 million times 22.4% times 2.06% or 27,917 older adults in hospitals who suffer from life-threatening heart toxicity from digoxin. This estimate understates the magnitude of the problem because the proportion of patients in the Miller/Greenblatt book using digoxin and experiencing life-threatening heart toxicity is based on all patients of all ages, whereas the rate of digoxin use and therefore the rate of life-threatening reactions is higher in older adults. The estimate is also lower because it does not include cases of digoxin toxicity that occur in surgical patients. 3 Ray WA, Griffin MR, Shorr RI. Adverse drug reactions and the elderly. Health Affairs 1990; 9: 114 - 122. 4 Ray WA, Fought RL, Decker MD. Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. American Journal of Epidemiology Oct 1, 1992; 136: 873 - 883. 5 The estimate of 32,000 hip fractures in older adults is based on projecting the findings of this study of drug-induced hip fractures in older Michigan Medicaid patients to the entire country. 6 Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ. Psychotropic drug use and the risk of hip fracture. New England Journal of Medicine Feb 12, 1987; 316: 363 - 369. 7 Myers AH, Robinson EG, Van Natta ML, Michelson JD, Collins K, Baker SP. Hip fractures among the elderly: Factors associated with in-hospital mortality. American Journal of Epidemiology Nov 15, 1991; 134: 1128 - 1137. 8 This estimate is based on projecting the findings of the Larson study on the 1.43 million Americans 65 and older who have dementia. See discussion on sleeping pills and tranquilizers (p. xxx) for more details about this serious problem. 9 Larson EB, Kukull WA, Buchner D, Reifler BV. Adverse drug reactions associated with global cognitive impairment in elderly persons. Annals of Internal Medicine Aug 1987; 107: 169 - 173. 10 See discussion on sleeping pills and tranquilizers (p. xxx) for more details on this estimate. 11 See discussion on antipsychotic drugs (p. xxx) for more details about drug-induced tardive dyskinesia and misprescribing of antipsychotic drugs. 12 The estimate of 61,000 older adults suffering from drug-induced parkinsonism is derived as follows: As described in detail in the chapter on antipsychotic drugs (see p. xxx), there are an estimated 750,000 people 65 and older in nursing homes or living in the community who are regularly (for three or four months or longer) being prescribed antipsychotic drugs. According to a survey in 1981 of 5,000 patients being treated with antipsychotic drugs, 13.2% had parkinsonism (see reference 15 below and p. xxx in the Mind Drugs section for further discussion of this problem). Another study by the same researchers found that 62% became better (no longer had parkinsonism) within 30 days of discontinuing the drug. Thus, at least 62% of the 13.2% of patients getting antipsychotic drugs or 7.92% of all patients getting these drugs suffer from drug-induced parkinsonism. Calculating 7.92% of 750,000 patients getting these drugs for at least several months yields 61,380 patients with drug-induced parkinsonism. This is a very conservative estimate because it does not include either those patients using antipsychotic drugs for less than three to four months (an additional 1.16 million people) who are also at risk for drug-induced parkinsonism (because 90% of the cases occur within 72 days after beginning the drug) or those who get drug-induced parkinsonism from the related drugs metoclopramide/REGLAN, prochlorperazine/COMPAZINE and promethazine/PHENERGAN usually prescribed for nausea. 13 Vestal RE;, ed. Drug Treatment in the Elderly. Sydney, Australia: ADIS Health Science Press, 1984. 14 Ouslander JG. Drug therapy in the elderly. Annals of Internal Medicine Dec 1981; 95: 711 - 722. 15 Grimes JD. Drug-induced parkinsonism and tardive dyskinesia in nonpsychiatric patients. Canadian Medical Association Journal Mar 1, 1982; 126: 468. 16 Drugs for the Elderly. 2nd edition. Copenhagen, Denmark: World Health Organization, 1997: 28. 17 Lipton HL, Bero LA, Bird JA, McPhee SJ. The impact of clinical pharmacists' consultations on physicians' geriatric drug prescribing: A randomized controlled trial. Medical Care Jul 1992; 30: 646 - 658. 18 Davies DM;, ed. Textbook of Adverse Drug Reactions. New York: Oxford University Press, 1977. 19 Aronson JK;Van Boxtel C;, ed. Side Effects of Drugs Annual 18. Amsterdam: Elsevier, 1995. 20 Drugs for the Elderly. 2nd edition. Copenhagen, Denmark: World Health Organization, 1997: 28. 21 Aronson JK;, ed. Side Effects of Drugs Annual 24. Amsterdam: Elsevier, 2001. 22 Drugs that may cause psychiatric symptoms. Medical Letter on Drugs and Therapeutics Jul 8, 2002; 44: 59 - 62. 23 Aronson JK;, ed. Side Effects of Drugs Annual 25. Amsterdam: Elsevier, 2002. 24 Other sources included the Physicians' Desk Reference and outside consultants. 2000-2005 Public Citizen's Health Research Group. All rights reserved.