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Adverse drug effects: New information about an old problem
Drug Consult Adverse Drug Effects: New Information about an Old Problem Carol A. Miller, RNC, MSN
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nformation about commonly occurring adverse drug effects is available as soon as drugs are approved by the Food and Drug Administration (FDA); however, information about drug interactions, just one type of adverse drug effect, evolves only after a medication has been used at least several months in the general population. Information about drug interactions is based on reports sent to the FDA after prescribing practitioners have identified such interactions in people taking other drugs; thus, it may take several years before accurate conclusions about drug interactions are made. This problem was illustrated recently when cerivastatin (Baycol) was recalled in August 2001, after being on the market for several years, because this statin drug had a much higher incidence of serious adverse effects than did the previously approved statin drugs. The incidence of adverse effects of cerivastatin was found to be significantly higher among older patients and in combination with another lipid-lowering drug, gemfibrozil. New information also may emerge about drugs that have been used for many years as studies are done on interactions and special populations, such as the elderly. For example, a recent study found that the coprescription of nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors are more likely than either drug alone to cause acute renal failure in patients 75 and older, especially if they also are taking a diuretic. Although NSAIDs and ACE inhibitors have been used for years, only recently has the potentiating effects of these drugs been studied. Another recent finding about long-used drugs is that the vaginal antifungal agent miconazole, available in prescription and nonprescription doses, is likely to interact with coumadin to increase blood levels of coumadin. Many new drugs are being developed and marketed because they have a better safety profile than older drugs. For example, the two newest NSAIDs, celecoxib
336
(Celebrex) and rofecoxib (Vioxx), have been promoted because they are safer than their predecessors for people with hypertension or a history of gastrointestinal bleeding. Recent evidence, however, raises questions about whether the newer NSAIDs are more likely than the older ones to cause renal damage. Until more evidence is collected, questions will remain about the adverse effects of these drugs.1 Similarly, newer atypical antipsychotics are promoted because they are less likely than older versions to cause extrapyramidal symptoms or tardive dyskinesia. Olanzapine (Zyprexa) and quetiapine (Seroquel) are atypical antipsychotics now widely used for older people with dementia because they are thought to have a better safety profile than other antipsychotics. Recent reports, however, suggest that these newer antipsychotics may be associated with new onset hyperglycemia, glucose intolerance, or type 2 diabetes.2 A related problem with newly approved drugs is that little information is likely available about their effects in people who have conditions other than the pathologic conditions for which the drugs are recommended. This situation is particularly problematic for older adults because they tend to have more concomitant illnesses and take more medications. For instance, many medications have a tendency to increase blood glucose, increasing the risk of adverse effects for people with diabetes. Some of the drugs and drug classes that may be particularly problematic for diabetics are niacin, diuretics, corticosteroids, sympathomimetics, beta-adrenergic antagonists, and estrogen-containing compounds. Nurses need to closely monitor the conditions of people with chronic conditions whenever medication changes are made. Case in point: estrogen therapy may increase the need for thyroid replacement hormone in women who have hypothyroidism. Another aspect of evolving information about drug interactions is the rapidly growing body of medical literature on mechanisms of drug metabolism, particularly in re-
Geriatric Nursing 2001 • Volume 22 • Number 6
lation to cytochrome P450 enzymes (CYPs). In recent years, intense interest is focusing on the more than 50 subtypes of human CYPs, the liver enzymes that prepare many drugs for elimination and significantly affect both the therapeutic and adverse effects. When two or more drugs metabolized by the same or a related CYP are taken together, drug/drug interactions are likely to occur. For example, cimetidine (Tagamet) interacts with many drugs across several types of CYPs. This mechanism may explain the increased incidence of adverse effects from statins, coumadin, psychotropics, antiarrhythmics, and many other types of drugs when taken with other drugs. These interactions include increased or decreased therapeutic effectiveness of either drug and an increased risk of adverse effects. Nutrients and other substances also affect many of the CYPs and account for some altered drug effects. Cigarette smoking reduces the blood concentrations of most neuroleptics and antidepressants by more than 50% because of the effect of tobacco components on CYPs.3 Competitive activity at CYP sites also explains the increased concentrations of certain drugs, such as statins and psychotropics, when taken with grapefruit juice. Drug interactions caused by competitive binding at CYP sites may be delayed if one of the two drugs has a long half-life. For instance, both coumadin and amiodarone compete at the same CYP site, but the long half-life of amiodarone may delay the full inhibitory effects for several months.4 With so much information about drug interactions lacking at the time of FDA approval of new drugs, it is not surprising that many geriatricians discourage using new medications in older people until the drugs have been on the market at least a year. Because nurses are responsible for knowing the therapeutic and adverse effects of the drugs they administer, geriatric nurses need to be especially vigilant when a recently approved drug is prescribed for an older adult who is taking other medications or has other medical conditions. Nurses may have to be detectives when they notice a change in an older adult taking more than one medication. They always need to consider the possibility that the change in condition may be related to a medication, either by itself or in interaction with other drugs or substances. Furthermore, when older adults have a problem taking recently approved drugs, nurses need to consider the possibility that the person may be experiencing a drug interaction not yet documented in the medical literature. Because medicinal information is evolving, it is imperative that all drug regimens be reassessed frequently for potential drug interactions. Pharmacists can play an active role in monitoring drug regimens, and many are using computerized systems to identify potentially dangerous drug/drug interactions. Finally, the FDA website (www.fda.gov/medwatch) is a good reference point for finding most up-to-date information about drug interactions and other adverse drug effects.
Geriatric Nursing 2001 • Volume 22 • Number 6
REFERENCES 1. Adhiyamam V, Asghar M, Oke A, White AD, Shah IU. Nephrotoxicity in the elderly due to co-prescription of angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs. J R Soc Med 2001;94:512-4. 2. Liebzeit KA, Markowitz JS, Caley CF. New onset diabetes and atypical antipsychotics. Eur Neuropsychopharmacol 2001;11(1):25-32. 3. Lin KM, Smith MW, Ortiz V. Culture and psychopharmacology 2001;24:52338. 4. Anderson JR, Nawarskas JJ. Cardiovascular drug-drug interactions. Cardiol Clin 2001;19:215-34.
CAROL A. MILLER, RNC, MSN, is a gerontologic nurse specialist with Care & Counseling, Miller/Wetzler Associates in Cleveland, Ohio. Geriatr Nurs 2001;22:336-7 Copyright © 2001 by Mosby, Inc. 0197-4572/2001/$35.00 + 0 34/1/120999 doi:10.1067/mgn.2001.120999
337
I
nformation about commonly occurring adverse drug effects is available as soon as drugs are approved by the Food and Drug Administration (FDA); however, information about drug interactions, just one type of adverse drug effect, evolves only after a medication has been used at least several months in the general population. Information about drug interactions is based on reports sent to the FDA after prescribing practitioners have identified such interactions in people taking other drugs; thus, it may take several years before accurate conclusions about drug interactions are made. This problem was illustrated recently when cerivastatin (Baycol) was recalled in August 2001, after being on the market for several years, because this statin drug had a much higher incidence of serious adverse effects than did the previously approved statin drugs. The incidence of adverse effects of cerivastatin was found to be significantly higher among older patients and in combination with another lipid-lowering drug, gemfibrozil. New information also may emerge about drugs that have been used for many years as studies are done on interactions and special populations, such as the elderly. For example, a recent study found that the coprescription of nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors are more likely than either drug alone to cause acute renal failure in patients 75 and older, especially if they also are taking a diuretic. Although NSAIDs and ACE inhibitors have been used for years, only recently has the potentiating effects of these drugs been studied. Another recent finding about long-used drugs is that the vaginal antifungal agent miconazole, available in prescription and nonprescription doses, is likely to interact with coumadin to increase blood levels of coumadin. Many new drugs are being developed and marketed because they have a better safety profile than older drugs. For example, the two newest NSAIDs, celecoxib
336
(Celebrex) and rofecoxib (Vioxx), have been promoted because they are safer than their predecessors for people with hypertension or a history of gastrointestinal bleeding. Recent evidence, however, raises questions about whether the newer NSAIDs are more likely than the older ones to cause renal damage. Until more evidence is collected, questions will remain about the adverse effects of these drugs.1 Similarly, newer atypical antipsychotics are promoted because they are less likely than older versions to cause extrapyramidal symptoms or tardive dyskinesia. Olanzapine (Zyprexa) and quetiapine (Seroquel) are atypical antipsychotics now widely used for older people with dementia because they are thought to have a better safety profile than other antipsychotics. Recent reports, however, suggest that these newer antipsychotics may be associated with new onset hyperglycemia, glucose intolerance, or type 2 diabetes.2 A related problem with newly approved drugs is that little information is likely available about their effects in people who have conditions other than the pathologic conditions for which the drugs are recommended. This situation is particularly problematic for older adults because they tend to have more concomitant illnesses and take more medications. For instance, many medications have a tendency to increase blood glucose, increasing the risk of adverse effects for people with diabetes. Some of the drugs and drug classes that may be particularly problematic for diabetics are niacin, diuretics, corticosteroids, sympathomimetics, beta-adrenergic antagonists, and estrogen-containing compounds. Nurses need to closely monitor the conditions of people with chronic conditions whenever medication changes are made. Case in point: estrogen therapy may increase the need for thyroid replacement hormone in women who have hypothyroidism. Another aspect of evolving information about drug interactions is the rapidly growing body of medical literature on mechanisms of drug metabolism, particularly in re-
Geriatric Nursing 2001 • Volume 22 • Number 6
lation to cytochrome P450 enzymes (CYPs). In recent years, intense interest is focusing on the more than 50 subtypes of human CYPs, the liver enzymes that prepare many drugs for elimination and significantly affect both the therapeutic and adverse effects. When two or more drugs metabolized by the same or a related CYP are taken together, drug/drug interactions are likely to occur. For example, cimetidine (Tagamet) interacts with many drugs across several types of CYPs. This mechanism may explain the increased incidence of adverse effects from statins, coumadin, psychotropics, antiarrhythmics, and many other types of drugs when taken with other drugs. These interactions include increased or decreased therapeutic effectiveness of either drug and an increased risk of adverse effects. Nutrients and other substances also affect many of the CYPs and account for some altered drug effects. Cigarette smoking reduces the blood concentrations of most neuroleptics and antidepressants by more than 50% because of the effect of tobacco components on CYPs.3 Competitive activity at CYP sites also explains the increased concentrations of certain drugs, such as statins and psychotropics, when taken with grapefruit juice. Drug interactions caused by competitive binding at CYP sites may be delayed if one of the two drugs has a long half-life. For instance, both coumadin and amiodarone compete at the same CYP site, but the long half-life of amiodarone may delay the full inhibitory effects for several months.4 With so much information about drug interactions lacking at the time of FDA approval of new drugs, it is not surprising that many geriatricians discourage using new medications in older people until the drugs have been on the market at least a year. Because nurses are responsible for knowing the therapeutic and adverse effects of the drugs they administer, geriatric nurses need to be especially vigilant when a recently approved drug is prescribed for an older adult who is taking other medications or has other medical conditions. Nurses may have to be detectives when they notice a change in an older adult taking more than one medication. They always need to consider the possibility that the change in condition may be related to a medication, either by itself or in interaction with other drugs or substances. Furthermore, when older adults have a problem taking recently approved drugs, nurses need to consider the possibility that the person may be experiencing a drug interaction not yet documented in the medical literature. Because medicinal information is evolving, it is imperative that all drug regimens be reassessed frequently for potential drug interactions. Pharmacists can play an active role in monitoring drug regimens, and many are using computerized systems to identify potentially dangerous drug/drug interactions. Finally, the FDA website (www.fda.gov/medwatch) is a good reference point for finding most up-to-date information about drug interactions and other adverse drug effects.
Geriatric Nursing 2001 • Volume 22 • Number 6
REFERENCES 1. Adhiyamam V, Asghar M, Oke A, White AD, Shah IU. Nephrotoxicity in the elderly due to co-prescription of angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs. J R Soc Med 2001;94:512-4. 2. Liebzeit KA, Markowitz JS, Caley CF. New onset diabetes and atypical antipsychotics. Eur Neuropsychopharmacol 2001;11(1):25-32. 3. Lin KM, Smith MW, Ortiz V. Culture and psychopharmacology 2001;24:52338. 4. Anderson JR, Nawarskas JJ. Cardiovascular drug-drug interactions. Cardiol Clin 2001;19:215-34.
CAROL A. MILLER, RNC, MSN, is a gerontologic nurse specialist with Care & Counseling, Miller/Wetzler Associates in Cleveland, Ohio. Geriatr Nurs 2001;22:336-7 Copyright © 2001 by Mosby, Inc. 0197-4572/2001/$35.00 + 0 34/1/120999 doi:10.1067/mgn.2001.120999
337