An adverse drug reaction (ADR) is any unexpected, undesired, or excessive response to a medication that results in:
Adverse drug reactions are distinguished from adverse drug events, in which causality is uncertain, and side effects, which may be bothersome to the patient and necessitate a change in therapy but are not considered serious. Although some ADRs are the result of medication errors, many are not.
Types of ADRs
The Food and Drug Administration (FDA) classifies ADRs into 2 broad categories: Type A and Type B. Type A reactions are predictable reactions based on the primary or secondary pharmacologic effect of the drug. Dose-related reactions and drug-drug interactions are examples of Type A reactions. Type B reactions are unpredictable, are not related to dose, and are not the result of the drug's primary or secondary pharmacologic effect. Idiosyncratic and hypersensitivity reactions are examples of Type B reactions.
Dose-Related Reactions (Toxic Reactions):
In dose related reactions, the dose prescribed for the patient is excessive. Although a variety of mechanisms may interact, reasons for this type of reaction include:
Dose-related reactions are often the result of preventable errors in prescribing in which physiologic factors such as age, renal impairment, and weight were not considered sufficiently, or in inadequate therapeutic monitoring. Medications with narrow therapeutic ranges (digoxin, aminoglycosides, antiepileptic drugs) and those that require careful monitoring or laboratory testing (anticoagulants, nephrotoxic drugs) are most frequently implicated in dose-related reactions. Dose-related reactions usually are managed successfully by temporarily discontinuing the drug and then reducing the dose or increasing the dosing interval. In some instances, the toxic effects need to be treated with another agent (e.g., Digibind for digoxin toxicity or protamine for heparin toxicity). Appropriately timed therapeutic drug level monitoring, review of new drugs added to an existing regimen that may affect the drug level, and frequent assessment of relevant laboratory values are critical to safe medical management and prevention of dose-related reactions.
Drug-Drug Interactions:
Drug-drug interactions occur when the pharmacokinetic or pharmacodynamic properties of an individual drug affect another drug. Pharmacokinetics refers to the way the body processes a medication (absorption, distribution, metabolism, and elimination). In a drug-drug interaction, the pharmacokinetic properties of one drug can cause a change in drug concentration of another drug and an altered response. For example, one drug may block enzymes that metabolize a second drug. The concentration of the second drug is then increased and may become toxic or cause adverse reactions. Pharmacodynamic drug-drug interactions involve the known effects and side effects of the drugs. For example, two drugs with similar therapeutic effects may act together in a synergistic way. The increased antithrombotic effects that occur when warfarin and aspirin are taken together, or the increased central nervous system (CNS) depression that results when two drugs with CNS depressant effects potentiate each other, are examples of pharmacodynamic drug-drug interactions. Certain classes of drugs are more likely to result in serious drug-drug interactions, and patients receiving these agents should be monitored carefully. These medication classes include anticoagulants, oral hypoglycemic agents, nonsteroidal anti-inflammatory drugs, antihypertensives, antibiotics, antiepileptics, antiretrovirals, antidepressants, and antipsychotic agents.
Idiosyncratic Reactions:
Idiosyncratic reactions occur without relation to dose and are unpredictable and sporadic. Reactions of this type may manifest in many different ways, including fever, blood dyscrasias, cardiovascular effects, or mental status changes. The time frame between the occurrence of a problem and initiation of therapy is sometimes the only clue linking drug to symptom. Some idiosyncratic reactions may be explained by genetic differences in drug-metabolizing enzymes.
Hypersensitivity Reactions:
Hypersensitivity reactions are usually allergic responses. Manifestations of hypersensitivity reactions range from mild rashes, to nephritis, pneumonitis, hemolytic anemia, and anaphylaxis. Protein drugs (vaccines, enzymes) are frequently associated with hypersensitivity reactions. In most instances, antibody formation is involved in the process and therefore cross-sensitivity may occur. An example of this is hypersensitivity to penicillin and cross-sensitivity with other penicillins and/or cephalosporins. Documenting drugs to which the patient is allergic and the specific hypersensitivity reaction is very important. If the reaction to an agent is anaphylaxis, the nurse should monitor the patient during administration of a cross-hypersensitive agent, especially during the initial dose, and ensure ready access to emergency resuscitative equipment.
Recognizing an ADR
Adverse drug reactions should be suspected whenever there is a negative change in a patient's condition, particularly when a new drug has been introduced. Strategies that can enhance recognition include knowing the side effect/adverse reaction profile of medications. Nurses should be familiar with a drug's most commonly encountered side effects and adverse reactions before administering it. In Davis's Drug Guide for Nurses, most frequent ADRs are underlined, and life-threatening ADRs are CAPITALIZED and appear in second color in the Adverse Reactions and Side Effects section. Within each organ system in this section, ADRs occurring at a frequency of ≥10% are underlined and are listed first (in alphabetical order). Adverse drug reactions occurring at a frequency of <10% will not be underlined and will be listed (in alphabetical order) after the underlined ADRs. As always, monitoring the patient's response to a medication and ongoing assessment are key nursing actions. Learn to recognize patient findings that suggest an ADR has occurred. These include:
Any of these findings can suggest an ADR and should be reported and documented promptly so that appropriate interventions, including discontinuation of suspect medications, can occur. Prompt intervention can prevent a mild adverse reaction from escalating into a serious health problem. Other steps taken by the health care team when identifying and treating an ADR include:
Prevention
Health care organizations have responded to consumer, regulator, and insurer pressures by developing programs that aim to eliminate preventable ADRs. In the inpatient setting, computer systems can display the patient's age, height, weight, and creatinine clearance (or estimated glomerular filtratration rate) and send an alert to the clinician if a prescribed dose is out of range for any of the displayed parameters. Allergy alerts and drug-drug interaction alerts can be presented to the clinician at the time an order is entered.
In the outpatient setting, strategies that increase the patient's knowledge base and access to pharmacists and nurses may help prevent adverse reactions. Outpatient pharmacy computer systems that are linked within a chain of pharmacies may allow the pharmacist to view the patient's profile if the patient is filling a prescription in a pharmacy other than the usual one. Many pharmacy computers have dose limits and drug-drug interaction verification to assist pharmacists filling orders.
Such strategies are a valuable auxiliary to, but cannot replace, conscientious history taking, careful patient assessment, and ongoing monitoring. A thorough medication history including all prescription and nonprescription drugs, all side effects and adverse reactions encountered, allergies, and all pertinent physical data should be available to the prescriber. The prescriber is responsible for reviewing this data, along with current medications, laboratory values, and any other variable that affects drug response.
It is not expected that practitioners will remember all relevant information when prescribing. In fact, reliance on memory is error-fraught, and clinicians need to use available resources to verify drug interactions whenever adding a new drug to the regimen. Setting expectations that clinicians use evidence-based information rather than their memories when prescribing, dispensing, administering, or monitoring patients has the potential to reduce the incidence of preventable ADRs.
Reporting ADRs in the U.S.:
Food and Drug Administration MedWatch Program:
To monitor and assess the incidence of adverse reactions, the FDA sponsors MedWatch, a program that allows health care practitioners and consumers the opportunity to report serious adverse reactions or product defects encountered from medications, medical devices, special nutritional products, or other FDA-regulated items. The FDA considers serious those reactions that result in death, life-threatening illness or injury, hospitalization, disability, congenital anomaly, or those that require medical/surgical intervention.
In addition to reporting serious ADRs, health care providers should also report problems related to suspected contamination, questionable stability, defective components, or poor packaging/labeling. Reports should be submitted even if there is some uncertainty about the cause/effect relationship or if some details are missing. This reporting form may be accessed at https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program. Reactions to vaccines should be reported to the Vaccine Adverse Event Reporting System (VAERS; https://vaers.hhs.gov/). Nurses share with other health care providers an obligation to report adverse reactions to the MedWatch program so that all significant data can be analyzed for opportunities to improve patient care.
Reporting ADRs in Canada:
The Marketed Health Products Directorate of Health Canada coordinates ADR reporting activities, and analyzes reports submitted from regional centers in each province. MedEffect Canada encourages health professionals, patients and regulatory authorities to report adverse reactions as they occur, either by email, mail, or the Health Canada website. Health care professionals reporting ADRs are required to supply information regarding patient characteristics, details about the reaction(s), current treatment, and outcomes. Information identifying the patient or health care provider remains confidential.
Adverse drug reaction reports are analyzed to investigate any associations with the health product. Based on the outcome, regulatory bodies decide on a course of action, which may include performing additional post-marketing studies, reassessment of the risk versus benefit of the product, packaging modification, addition of warnings in patient information leaflets, or issuing public alerts or market withdrawals. Updates regarding adverse reactions are published in the Health Product InfoWatch every month.
Access the following link for the Side Effect Reporting Form for consumers and health professionals: https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html.