Chapter 7

1. Chapter 7 Adverse Drug Reactions and Medication Errors

2. Two Related Issues of Drug Safety • Adverse drug reactions (ADRs) • Also known as adverse drug events (ADEs) • Medication errors

3. Adverse Drug Reactions • Defined by the World Heath Organization • Any noxious, unintended, and undesired effect that occurs at normal drug doses • Excludes excessive dosages • Can range from annoying to life-threatening

4. Adverse Drug Reactions • Scope of the problem • Mild reactions • Drowsiness, nausea, itching, and rash • Severe reactions (potentially fatal) • Respiratory depression, neutropenia, hepatocellular injury, anaphylaxis, hemorrhage • Most common in the elderly and very young • Risk increased by severe illness • Possibly 110,000 deaths a year due to ADRs

5. Terms Related to Adverse Drug Reactions • Side effect • Toxicity • Allergic reaction • Idiosyncratic effect • Iatrogenic disease • Physical dependence • Carcinogenic effect • Teratogenic effect

6. Terms Related to Adverse Drug Reactions cont’d • Organ-specific toxicity • Kidneys • Lungs • Inner ear • Heart • QT interval • Liver

7. Terms Related to Adverse Drug Reactions • Side effect • A nearly unavoidable secondary drug effect produced at therapeutic doses • May develop soon after drug is initiated or not until drug has been taken for weeks or months • Toxicity • Formal definition: adverse drug reaction caused by excessive dosing • May occur even with normal dosing • Neutropenia (risk for infection) and anticancer medications

8. Terms Related to Adverse Drug Reactions • Allergic reaction • Immune response • Determined primarily by the degree of sensitization of the immune system,not by drug dosage • Patient’s sensitivity to a drug can change over time. • Very few drugs cause severe allergic reaction. • Penicillins are the most common. • Allergies may also be induced by sulfonamides (diuretics, antibiotics, and oral hypoglycemic agents).

9. Terms Related to Adverse Drug Reactions • Idiosyncratic effect • An uncommon drug response resulting from a genetic predisposition • Succinylcholine-induced paralysis • Usually brief • May last for hours in genetically predisposed patient

10. Terms Related to Adverse Drug Reactions • Iatrogenic disease • iatros = a Greek word meaning “physician” • genic = a combining form meaning “to produce” • iatrogenic = literally, “a disease produced by a physician,” also used to refer to a disease produced by drugs (eg, drugs for antipsychotic disorders can cause Parkinson’s-like symptoms) • Sometimes also called drug-induced disease • Essentially identical to naturally occurring pathology

11. Terms Related to Adverse Drug Reactions • Physical dependence • Develops during long-term use of certain drugs (opioids, alcohol, barbiturates, and amphetamines) • A state in which the body has adapted to drug exposure in such a way that • An abstinence syndrome will result if drug use is discontinued • Important to warn patients against abrupt discontinuation of any medication without first consulting a knowledgeable health professional

12. Terms Related to Adverse Drug Reactions • Carcinogenic effect • Only a few therapeutic agents are carcinogenic. • Several drugs used to treat cancer are among those with the greatest carcinogenic potential. • Evaluating drugs is difficult; it may take decades for evidence of carcinogenesis after exposure. • An example is diethylstilbestrol (DES). • Teratogenic effect • Drug-induced birth defect • More discussion of this topic in Chapter 9

13. Adverse Drug Reactions • Organ-specific toxicity • Many drugs are toxic to specific organs. • Common examples include • Kidneys: amphotericin B (antifungal) • Heart: doxorubicin (anticancer) • Lungs: amiodarone (antidysrhythmic) • Inner ear: aminoglycoside (antibiotic)

14. Organ-Specific Toxicity • Hepatotoxic drugs • QT interval drugs

15. Hepatotoxic Drugs • Leading cause of liver failure in the United States • More than 50 drugs are known to be hepatotoxic. • As some drugs undergo metabolism, they are converted to toxic products that can injure liver cells. • Combining hepatotoxic drugs may increase the risk for liver damage—for example, acetaminophen and alcohol. • Monitor aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for liver injury. • Watch for signs of liver injury; educate patient: • Jaundice, dark urine, light-colored stools, nausea, vomiting, malaise, abdominal discomfort, loss of appetite

17. QT Interval Drugs: More Than 100 Are Known • QT interval: measure of the time required for the ventricles to repolarize after each contraction • QT drugs: the ability of some drugs to prolong the QT interval on electrocardiography (ECG) • Creates serious risk of life-threatening dysrhythmias • Examples: torsades de pointes, V-fib • Minimizing the risk • Patients at higher risk include women, the elderly, and patients with bradycardia, congestive heart failure (CHF), congenital QT prolongation, low potassium, and low magnesium. • Do not use two QT drugs concurrently.

19. Identifying Adverse Drug Reactions • Can be very difficult to determine whether a specific drug is responsible for an observed adverse event • Other factors to consider • Underlying illness • Other drugs

20. Identifying Adverse Drug Reactions • Did symptoms appear shortly after the drug was first used? • Did symptoms abate when the drug was discontinued? • Did symptoms reappear when the drug was reinstituted? • Is the illness itself sufficient to explain the event? • Are other drugs in the regimen sufficient to explain the event?

21. Adverse Reactions to New Drugs • 50% of all new drugs have serious ADRs that are not revealed during Phase II and Phase III trials. • Be alert for unusual responses when giving new drugs. • Drugs that you suspect of causing a previously unknown adverse effect should be reported to • MedWatch: the FDA Medical Products Reporting Program

22. Ways to Minimize Adverse Drug Reactions • Responsibility for reducing ADRs lies with everyone associated with drug production and usage • Prescriber: select the least harmful drug. Balance potential risks versus probable benefit. • Nurse: evaluate patient for ADRs and educate patients and families on how to minimize harm. • Patients and families: watch for signs an ADR may be developing and notify health care provider.

23. Ways to Minimize Adverse Drug Reactions • Anticipation of ADRs can help minimize them. • Target evaluation of the function of any at-risk organs • Important sites of toxicity • Liver: signs of jaundice; monitor liver function tests (LFTs) • Kidney: routine urinalysis and serum creatinine (periodic creatinine clearance) • Bone marrow: periodic blood cell counts • Patients with chronic disorders are especially vulnerable to ADRs.

24. Boxed Warnings • Black box warnings • Strongest safety warning a drug can carry and still remain on the market • Concise summary of the adverse effects of concern • Text is presented inside a box with a heavy black border.

25. Medication Errors • Major cause of morbidity and mortality • Documented in two landmark reports from the Institute of Medicine: • To Err Is Human—1999 • Preventing Medication Errors—2006 • It is estimated that medication errors • Injure 1.5 million people per year • Kill 7000 people per year

26. Medication Errors • Defined by the National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) as • “. . .any preventable event that may cause or lead to inappropriate medication use or patient harm, while the medication is in the control of the healthcare professional, patient, or consumer. Such events may be related to professional practice, healthcare products, procedures, and systems, including prescribing; order communication, product labeling, packaging and nomenclature, compounding, dispensing; distribution, administration; education, monitoring; and use”

27. Medication Errors • Risk for error in hospitals is high because each medication order is processed by several people. • The nurse is the last person in this sequence. • Thus, the nurse is the last line of defense against mistakes. • This places a heavy responsibility on the nurse for ensuring patient safety.

28. Types of Medication Errors • Fatal medication errors • Overdose: 36.4% • Wrong drug: 16.2% • Wrong route: 9.5%

30. Causes of Medication Errors • 90% of all errors are due to • Human factors • Communication mistakes • Name confusion

33. Ways to Reduce Medication Errors • Help and encourage patients and their families to be active, informed members of the health care team. • Create an institutional culture dedicated to safety. • Give health care providers the tools and information they need to prescribe, dispense, and administer drugs as safely as possible. • Institute safety checklists for high-alert drugs. • About 20 drugs cause 80% of medication error-related deaths.

34. Ways to Reduce Medication Errors • Replace handwritten medication orders with a computerized order entry system. • Have a senior clinical pharmacist accompany physicians on rounds. • Use a bar-code system. • Do not use error-prone abbreviations. • See Table 7-7.

35. Ways to Report Medication Errors • Medication Errors Reporting (MER) program • Reporting is confidential. • Reporting can be done by phone, fax, or Internet. • Program encourages all health care providers, including pharmacists, nurses, physicians, and students, to report errors. • www.usp.org/hqi/patientSafety/mer/ • All information is forwarded to the Food and Drug Administration (FDA), the Institute for Safe Medication Practices (ISMP), and the product manufacturer