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Southern Medical Journal:
doi: 10.1097/SMJ.0b013e3181f5ecb5
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Adverse Drug Reactions: Part II

Wooten, James M. PharmD

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Author Information

From the Department of Medicine, School of Medicine, University of Missouri-Kansas City, Kansas City, MO.

Reprint requests to James M. Wooten, PharmD, Department of Medicine, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108. Email: wootenj@umkc.edu

Dr. Wooten has no financial disclosures to declare or conflicts of interest to report.

Accepted June 16, 2010.

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Abstract

Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.

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Key Points

* Certain patients and population groups may be more prone to particular adverse drug reactions (ADRs) than other patient types. Stratifying those patients in whom ADRs may be more prevalent is important, as this can help identify patients at greatest risk.

* ADRs are most prevalent in the elderly, children, and pregnant patients.

* Current research regarding pharmacogenetics suggests that patients may respond to and metabolize drugs in different ways. Besides variations from one individual to another, there may also be distinct variances in how patients of different ethnicities handle different drugs. Patients with specific genetic characteristics (not necessarily related to ethnicity) may be more prone to specific adverse reactions.

* Postmarketing surveillance is of primary importance in identifying and preventing ADRs associated with new drugs. Only the most prevalent ADRs will be identified in the pre-approval (Phase I, Phase II, and Phase III clinical trials) process.

* All health care providers should be intimately involved in the reporting process for adverse drug reactions. It is everyone's responsibility.

This article continues the exploration of adverse drug reactions (ADRs) begun in the Southern Medical Journal's October issue.1 In “Adverse Drug Reactions: Part I,” the science of pharmacovigilance was discussed, with an emphasis on recognizing and preventing potential ADRs before they occur. Part I also detailed the classification scheme used to define ADRs, and defined and discussed different types of “drug allergies.” In this article, patient populations at risk for ADRs are identified, and strategies for reducing the risk of ADRs in these populations are discussed. The importance of postmarketing information in the reduction of ADRs is examined, and some general techniques for preventing ADRs are listed.

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Risk Factors for Adverse Drug Reactions

Certain patients and population groups may be more prone to particular ADRs than other patient types. Stratifying those patients in whom ADRs may be more prevalent is important, as this can help identify patients at greatest risk. Certain patient characteristics play an important role in helping to identify those patients at greatest risk for developing an ADR. Polypharmacy is a universal risk.2,3 The incidence of ADRs increases greatly as the number of medications rises.2,3 Any patient with hepatic or renal disease is also at greater risk for developing an ADR. As drug clearance is reduced, the risk of drug-induced side effects is increased.4,5

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The Elderly

ADRs are quite common in elderly patients. Approximately 20% of the United States population can be defined as elderly, and this 20% accounts for approximately 33% of all prescription drug use.6 It is no wonder, then, that ADRs are more common in the elderly. Other considerations also make ADRs more common in older patients (Table 1).2,3,7

Table 1
Table 1
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The pharmacokinetics of many drugs may be altered in geriatric patients. Renal and hepatic clearance of drugs is reduced as the aging process progresses, which results in higher drug concentrations. Protein binding of certain drugs may be reduced in the elderly, leading to more free drugs, which can result in an amplified pharmacologic response. Drugs that undergo extensive first-pass metabolism may have a greater response in geriatric patients, since first-pass hepatic metabolism is reduced as one ages.2,6,7

Elderly patients usually take more medications than the rest of the population. This means the potential for drug-drug or drug-disease state interactions is much higher in these patients. Because of a greater number of comorbidities, older patients generally have a reduced tolerance for these changes. In other words, drug side effects may occur in elderly patients because they are least able to tolerate them. Premarketing trials with drugs may include elderly patients, but seldom do these studies include all types of patients with all types of diseases who may be receiving a varied assortment of chronic medications. Because the combinations are endless, the variety of potential side effects and the rate at which these side effects may occur are also endless. With new drugs, especially, unknown adverse effects should be expected, and this necessitates careful patient monitoring.2,3,6,8

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Strategies to Reduce the Risk of ADRs in the Elderly

1. When prescribing medications for elderly patients, the Latin phrase “Primum non nocere” should come to mind.2,3,6,7 The translation of this phrase, “First, do no harm,” means that whatever is prescribed must do less harm than prescribing nothing.

2. If possible, review a patient's medication list to see if a drug can be discontinued when prescribing a new drug for that patient.

3. Because the pharmacokinetics of many drugs are altered in the elderly, the dosing needs to be reduced. The titration of doses can occur at a slow rate.

4. Elderly patients should be encouraged to bring all of their medications to each appointment (“brown bagging it”). This way, caregivers know exactly what is being taken by the patient.

5. It sounds obvious, but stop unnecessary drugs. Does the patient need a laxative or a sleeping agent? Can various prn (as needed) drugs be discontinued? The excuse some health care providers give is, “I do not want to stop taking anything started by another physician.” This may or may not be the prudent thing to do. At the least, review every medication the patient is taking and make sure they make sense.

6. Review the common side effects of each drug with the patient and assess the patient's risk for developing that side effect.

7. Remember, just because the patient has been taking a medication for a long time does not mean that he/she cannot be experiencing side effects. Because the aging process alters the pharmacokinetics of many drugs, side effects will be more common.

8. Adverse drug reactions should be considered the rule, rather than the exception. Every differential should include “drug-induced causes.”

9. Stay away from “problem drugs” in the elderly. The Beers Criteria are a list of the most common drugs known to cause problems in the elderly. If these drugs are prescribed, a reduced dose should be used. Know what these problem drugs are.10

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Children

Like the elderly, children may also be at greater risk for developing ADRs than the general public. As in the elderly, the pharmacokinetics of drugs may be variable. The major reason why adverse drug reactions happen in children is that most medications are not studied adequately in a representative patient population to properly assess the dose, pharmacokinetics, and side effect profile. Significant differences may exist in how a small child (three to four years old) handles a compound compared to how a teenager handles the drug. Likewise, there may be significant differences in a neonate's reaction to a certain medication versus that of a toddler versus that of a teenager. Much of this information is required by the United States Food and Drug Administration (FDA) before listing children's dosing parameters in a drug's package literature. However, when a new drug comes on the market, there is little incentive for the company to continue research in children.11–14 As various drugs are used in children, the American College of Pediatrics may publish dosing parameters based on whatever research is conducted.11 Generally, this information is based on small patient populations, so side effects may not occur until the drug is utilized in more patients. As with the elderly, children may be ill-equipped to handle a particular adverse reaction, and any untoward effect has the potential to be quite serious. As in the elderly, very low doses should be used initially and titrated slowly. However, simply reducing the dose on a mg per kg basis may be very imprecise, since the pharmacodynamics of a particular drug may be completely different in a child as compared to an adult. Children can have variable side effects and small children may not be able to adequately communicate problems, so the practitioner must have a reliable way to monitor for adverse effects in the children he/she treats.11–14

For many drugs, the absorption characteristics may be different in children than in adults. Differences in how drugs are handled by the liver and the kidneys may also significantly alter the pharmacokinetics and the pharmacodynamics of a particular drug in a child. Even the administration of topical agents may yield quite different results in children, since the skin and epidermis of a child may be quite different than that of an adult. In addition, a suitable dosage formulation may not always be available for administration in children.11,12

Pharmacovigilance plays a very important role when prescribing drugs in children. Because of the paucity of information that may be available regarding the use of a particular drug in the pediatric population, a mechanism for data collection and reporting is essential. Physicians are encouraged to report to the FDA whatever information they encounter regarding specific drugs.15,16 Whenever a drug is used in a child, a thoughtful monitoring plan should be established so as to appropriately monitor efficacy and adverse events.11 Because children may not be able to express how they feel, caregivers must play an active role in this monitoring process and must be educated regarding appropriate medication use.

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Strategies to Reduce the Risk of ADRs in Children

1. Children are not simply “mini adults,” whereby reducing the dose on a mg per kg basis will produce similar therapeutic and toxic responses to those observed in adults.11–14 Because the pharmacokinetics and pharmacodynamics of drugs in children may differ from that of adults, the efficacy and side effect profile may be profoundly different.

2. Before any drug is prescribed to a pediatric patient, a thorough understanding of its pharmacology in that patient is vital.

3. Before any drug is prescribed to a pediatric patient, a plan must be established with the patient or the patient's caregivers for monitoring the efficacy of the drug, as well as how to monitor for potential adverse drug effects. Caregivers should be encouraged to record to keep a journal of any potential drug-related adverse effects, questions, or issues, especially for patients with serious diseases that require multiple medications.

4. As with the elderly, the potential for adverse drug reactions increases with the number of medications prescribed. Pharmacovigilance is vital, and the potential for drug-drug interactions is a major concern.

5. Adverse drug reactions can mimic other diseases, so understanding the side effect profile of any drug prescribed is essential to ensure appropriate medication use.

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Medication Use in the Pregnant Patient

Patients who are pregnant, who are trying to get pregnant, or even women of child-bearing age can be challenging to care for with pharmacotherapy because of the risk of teratogenic effects on the fetus. Adverse drug reactions in these patients could have devastating consequences. The first recommendation for these patients is to ensure that a pregnancy test is performed unless there is absolute certainty that the patient could not be pregnant. This is a very cost-effective test to ensure that no drug-related problems pose a hazard later on in treatment.

A clear discussion must occur between physician and patient to determine the patient's risk/chances of pregnancy at the time of the visit and in the future. Physicians and other health care workers who treat pregnant patients (or those who could become pregnant) must tailor drug treatment protocols to the specific desires and wishes of the patient. Medications which are known teratogens should be avoided if possible; if treatment with these drugs is necessary, the patient may need counseling on proper birth control precautions.17–20

Physicians who treat pregnant patients or patients who could become pregnant should understand the FDA's five letter rating system for the teratogenic effects of drugs and be able to utilize specific information to make safe and effective drug therapy decisions based on teratogenic potential (Table 2). Health care providers taking care of these patients must be current on treatment recommendations for common disease states in the pregnant patient (such as asthma in pregnancy, diabetes in pregnancy, epilepsy in pregnancy, etc). In addition, some drugs may be more or less harmful if taken at a particular time (trimester) during the pregnancy.17,18 To avoid potential problems to the fetus, some patients may need to be cared for by health care providers who specialize in treating potential problem pregnancies.

Table 2
Table 2
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Thoughtful consideration must be employed when selecting pharmacotherapy for patients who could become pregnant while taking specific medications. For instance, in treating a hypertensive female patient of child-bearing age, the use of an angiotensin converting enzyme (ACE) inhibitor should be avoided because of the potential teratogenic risk. However, if a particular drug or drug class is deemed absolutely necessary for proper care of the patient, the risk (in some instances) may be justified. Proper documentation and patient education is strongly encouraged.17–20

As with pregnancy, breastfeeding mothers require careful and prudent drug therapy selection. The risk of ADRs to the child via delivery of the drug in breast milk is a major concern. Much more information is now available to assess the risk potential of certain drugs in breastfeeding. Research should be conducted on a particular drug before it is prescribed to better determine the risk potential. Proper patient education is critical to minimize risk to the child.17–20

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Strategies to Reduce the Risk of ADRs in Pregnancy

1. Remember, if there is any chance at all that a patient could be pregnant, make sure a pregnancy test is performed before prescribing.

2. Generally, a healthy mother is more likely to deliver a healthy baby.17–20,22 Therefore, treating the mother properly is the best way to ensure a problem-free pregnancy.

3. If possible, patients with chronic conditions who wish to become pregnant should be advised to consult with physicians who specialize in treating various diseases in pregnant patients. This way, the pregnancy may progress uneventfully with no harm to the patient or the fetus.

4. Keep in mind when prescribing drugs to pregnant patients: the first trimester of pregnancy is generally the most critical. Early in pregnancy most cells are undifferentiated and drugs ingested by the mother at this time tend to affect all cells, which (if the drug is teratogenic) may result in a terminally toxic event. This does not preclude the fact that drug-induced teratogenic effects can also happen in the second or third trimester.

5. Avoid the use of many medications for one problem. Minimize the number of drugs and prescribe the safest ones.

6. If medications are prescribed, do the research and assess the risk to the fetus versus the benefit to the mother. There are now excellent resources and guidelines available to provide specific information on how to treat various diseases in pregnancy. Do the research before prescribing the drug.

7. Utilizing the FDA classification may be somewhat useful; however, the information provided often does not help much. That being said, the FDA is in the process of developing new guidelines for drug use during pregnancy.22

8. There are some drugs that must be avoided: methotrexate, warfarin, diethylstilbestrol, alcohol, retinoic acid, etc (this is not an all-inclusive list). Practitioners who prescribe these drugs to patients with child-bearing potential must understand the risks and provide proper patient counseling about the risks/benefits of a specific agent. If future pregnancy is desired, then a plan must be formulated with the patient to minimize harm to both patient and fetus.

9. As with pregnancy, certain drugs are safe and others should be avoided when breast feeding. Again, with proper planning, the best medications can be utilized based on the current scientific data. The FDA offers some information, and is working on ways to provide better information on drug effects during pregnancy and lactation.20

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Other Factors

Current research regarding pharmacogenetics suggests that patients may respond to and metabolize drugs in different ways. Besides variations from one individual to another, there may also be distinct variances in how patients of different ethnicities handle different drugs. For example, the risk of developing angioedema with ACE inhibitors appears to be greater in black patients than in non-black patients.23 The risk of developing a dry, nonproductive cough with ACE inhibitors appears to be more prevalent in East Asian patients.24 Understanding what causes these differences is key to being able to more accurately predict ADRs.25,26

Patients with specific genetic characteristics may be more prone to specific adverse reactions. These genetic differences may or may not be explained by ethnicity. There appears to be a definitive genetic association between a particular human leukocyte antigen (HLA)-B allele and a reaction to various drugs. Patients with this genetic variant appear to be at greater risk for developing cutaneous adverse drug reactions. Other genetic markers may also be present in some individuals. Another HLA (HLA-B*5701) subtype may be predictive of liver toxicity with certain medications. Patients who develop long QT Syndrome (Torsades de Pointes) may also have genetic factors that make this deadly side effect more common in these individuals.27–29

Using all of this information to predict the potential for ADRs is key. How can this information be obtained and assessed in a cost-effective manner? Which patients should have a genetic profile and why? Which ADRs should be deemed relevant enough to test for, and which are so mild that testing would prove to be cost inefficient? All of these options must be assessed and explained.29

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Why Postmarketing Information Is so Important

As discussed previously, one way of defining ADRs is based on their occurrence. Some ADRs are classified as common, others as uncommon, and still others as rare. In the United States all new drugs undergo extensive review, and the FDA requires a significant amount of safety data before approving a new drug for use. Unfortunately, most new drugs are only studied in a few thousand patients. This is important, because only the most prevalent ADRs will be identified in the pre-approval (Phase I, Phase II, and Phase III clinical trials) process. Less common events may not manifest themselves until the drug enters the market post-approval and the drug is utilized in several thousand more patients. Because of time, money, and the fact that it is so difficult to duplicate the exact patient population who might receive the drug, pre-approval studies are often unable to paint a true picture of the precise risks of the drug in patients who might be at greatest risk. Older or younger patients with various comorbidities—potentially receiving a myriad of different drugs—may have a completely different risk of developing an ADR from a new agent than those subjects included in premarketing trials. This is why postmarketing information is so vitally important, especially with new medications. Generally, a drug's complete adverse effect profile is not known until it has been on the market for several years.30–33 A list of some drugs removed from the market due to postmarketing surveillance may be seen in Table 3.

Table 3
Table 3
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Understanding that the FDA's process of new drug evaluation, known as the Center for Drug Evaluation and Research (CDER), cannot possibly identify all of the potential side effects caused by new or older pharmaceuticals, the FDA has implemented a thorough postmarketing surveillance system which strives to identify adverse events that do not appear during the drug approval process. A computerized information database known as the Adverse Event Reporting System (AERS) helps to collect and stratify data concerning all approved drugs and therapeutic biologic products. Drug information reports, data sheets, etc are constantly catalogued, reviewed, and analyzed by a multidisciplinary staff of safety evaluators, epidemiologists, and other scientists. In this way accurate information is ultimately provided to health care professionals and the public.35,36

Physicians and other health care workers should be familiar with the FDA's MedWatch program, which is a component of AERS and is structured to allow for voluntary reporting of serious reactions and problems with medical products such as drugs and medical devices. MedWatch tries to ensure that quality evidence is gathered and analyzed as quickly as possible to allow health workers to make the best possible pharmacotherapy decisions. The data collected via the MedWatch forms are invaluable, considering the fact that so much drug information is collected by postmarketing surveillance. The success of the MedWatch program depends on the vigilance of all health care providers. Unfortunately, many health care workers do not take the time to complete MedWatch reports, declaring it “takes to much time,” or the report is “too difficult to fill out,” or even, “no one's going to review this anyway.” All of these are poor excuses for failing to provide a vital service to the community. Admittedly, the MedWatch form does take some time to complete, but the information garnered from it is necessary to make important risk assessments on medications.31,37

Identifying a causal relationship between a drug and a particular adverse event can be difficult, especially if a patient is receiving many medications. The FDA relies on scientists, statisticians, and others to assess the huge amount of information it collects on medications and other health-related items. The goal is to provide current, evidence-based information to the public and to health care professionals to use in caring for patients. Various tools have been developed by the FDA and others to assess the probability of ADRs. One extensively used tool is the Naranjo ADR Probability Scale, which assigns a score to a particular event based on a series of questions.38 The derived score then determines the general probability of that particular drug causing a specific adverse drug reaction. Assessing the “cause/effect” of an ADR is especially important for postmarketing reports, as the drug is used in a less controlled environment than that of the premarketing randomized controlled trials.5,38

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Techniques for Monitoring ADRs

Hospital and community pharmacies have gotten creative in ways to monitor, identify, and report adverse drug reactions. It is very important that all health care workers (pharmacists, physicians, nurses, dentists, etc) be empowered to report adverse drug reactions. More reports mean more data, and more data translate into better evidence so that appropriate decisions can be made regarding the drug. Electronic medical records have enabled health care workers to identify, record, and report ADRs more quickly. The Internet has allowed health care workers and institutions to send reports to the FDA almost instantaneously. All of this translates into better health care.21,39,40

Hospitals, particularly, have been mandated to effectively monitor for adverse drug reactions. Because of the headlines generated by ADRs, health care policymakers attempt to remain at the forefront of prevention. The Joint Commission on Accreditation of Healthcare Organizations (a governing body which assesses the overall effectiveness of hospitals) now requires health care institutions to establish programs that monitor, track, and prevent ADRs and medication errors. Various techniques have been successful, including the following:21,39–41

* Patients receiving more than a designated number of scheduled medications have their medical record thoroughly reviewed and evaluated for ADRs and drug interactions. As was stated previously, the elderly are at risk for ADRs because they are generally on more medications and can at least tolerate side effects.

* Some hospitals monitor tracer drugs like diphenhydramine, corticosteroids, Vitamin K, and other antidotes to identify the occurrence of potential drug reactions.

* Some hospitals identify ADRs in specific patient types. For example, patients with human immunodeficiency virus (HIV) are at risk for a myriad of different drug reactions due to various antiretroviral therapies, as well as other pharmacotherapy. By prospectively monitoring these patients, common ADRs can be averted.

* Some hospitals are able to inform the nursing staff to be vigilant about monitoring for certain ADRs. For instance, when a vancomycin intravenous bag is sent to the floor, the label may indicate the particular rate at which to administer the drug in an effort to reduce the risk of “red man syndrome.”

* Hospitals now have extensive educational programs for nurses, physicians, residents, and students to educate them about ADRs, especially those associated with new drugs. Education is a key ingredient in ADR prevention.

It may be more difficult to monitor ADRs in the community, since the patient has less contact with a health care team. That being said, physicians, pharmacists, and nurses must be vigilant in preventing potential adverse effects from occurring. Pharmacy computer systems can alert health care providers to possible drug interactions. Information systems can collect patient data (renal function, hepatic function, age, number of medications) and identify those patients at greatest risk for developing an ADR. Patients in nursing homes must have their medications reviewed by a pharmacist periodically. All health care personnel must take the time to thoroughly review and discuss a patient's pharmacotherapy regimen when answering questions or counseling patients.42,43

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Conclusion

The science of pharmacology is quite dynamic. Because of novel and exciting scientific techniques and discoveries, the number of new medications being studied and approved to treat all different types of ailments is always expanding. Indeed, it is difficult for many physicians to keep up with the never-ending updates about new medications or pharmaceutical entities. Because of this, adverse drug reactions can never be entirely eliminated. In fact, their incidence will only increase, as more drugs lead to more drug-drug interactions and more ADRs.

Unfortunately, just being aware that ADRs exist is not good enough. ADRs can be so dangerous and debilitating that they should warrant more interest from health care professionals than they currently do. Adverse drug reactions are just as important as the disease states for which drugs were prescribed in the first place. The following points are important:

* Before prescribing a drug, know its pharmacology. How does it work? How is it eliminated? What are its side effects? How should it be dosed? How is its utilization monitored?

* If possible, health care professionals should avoid prescribing new drugs until they have been on the market for a sufficient amount of time so that postmarketing surveillance studies are available to assess the risks and benefits.

* Adverse drug reactions must be respected. Rather than thinking about them in a retrospective way, consider ADRs prospectively. Would an ADR from a particular drug be more or less common in a particular patient? How many of the drugs a patient is receiving are being prescribed to treat the side effects of other drugs (such as laxatives used to treat constipation caused by narcotic analgesics)?

* ADRs must be a prominent feature in the physician's history and physical (H&P). Every problem list should include “Potential ADRs.” This point should then be addressed in the assessment portion of the H&P, and should also be assessed in all subsequent daily SOAP (subjective, objective, assessment, and plan) notes. This will ensure that ADRs are always a major consideration when caring for patients, rather than a minor, insignificant factor.

* When patients are admitted through the emergency room (ER), a section of the ER admitting form should be devoted to “Potential Adverse Drug Reactions.”

* Health care professionals (nurses, physicians, pharmacists, etc) need better training in assessing, monitoring, and treating patients for adverse drug reactions.

* It would be beneficial if the FDA incorporated a user-friendly access point into its website for health professionals to easily report and review updates on all ADRs, not only from individual drugs, but also from different drug classes so that drugs in the same class can be easily compared.

* Pharmacists must have the responsibility and the technical ability to be able to consult with other prescribers and health care professionals about ADRs.

* Hospitals and long-term care facilities should have continuing education programs on ADRs yearly.

* Finally, all health care providers must be intimately involved in the reporting process for adverse drug reactions. It is everyone's responsibility.

Adverse drug reactions are an extremely important consideration when assessing a patient's health care. All health care professionals must be involved in the process for identifying, monitoring, reporting, and preventing adverse drug reactions. The science of pharmacovigilance must be practiced by all health care providers.

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Product Code: SMJ11-10B

Adverse Drug Reactions: Part II

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November 2010 CME Questions

1. Which patient would be a high risk for developing an adverse drug reaction (ADR)?

A. A patient currently receiving ten scheduled medications

B. A 90-year-old woman

C. A 40-year-old pregnant female

D. A six-month-old male in the neonatal intensive care unit

E. All of the above are considered high risk for developing an ADR

2. Which of the following regarding pharmacotherapy in the elderly is FALSE?

A. The protein binding of most drugs is increased in the elderly.

B. Lipophilic drugs may have an increased volume of distribution in the elderly.

C. The hepatic metabolism of drugs is generally reduced in the elderly.

D. The renal clearance of drugs is generally reduced in the elderly.

3. Which statement is TRUE?

A. In children, most medications are not studied adequately in a representative patient population to properly assess the dose, pharmacokinetics, and side effect profile.

B. Regarding medication use in pregnancy, if a drug is listed in the Food and Drug Administration (FDA) Pregnancy Category D, it is considered SAFE to use in the pregnant patient as there is no scientific evidence to suggest any harm to the fetus.

C. Drugs such as warfarin and methotrexate are listed in FDA Pregnancy Category A.

D. There is little evidence which suggests that genetic markers for identifying ADRs or drug interactions may be useful in certain patient populations.

Online CME Request Form

http://www.sma.org/medallion-level-cmece/cme-credit-form?pcode=SMJ11-10B

Figure.  2010
Figure. 2010
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November 2010 CME Questions — Answer Key

1. D, 2. D, 3. A

Keywords:

adverse drug reactions; adverse reactions; drugs; pharmacology

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© 2010 Southern Medical Association

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