Chapter 7
Adverse Drug Reactions and
Medication Errors
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Two Related Issues of Drug Safety
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Adverse drug reactions (ADRs)
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Also known as adverse drug events (ADEs)
Medication errors
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Adverse Drug Reactions
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Defined by the World Heath Organization
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Any noxious, unintended, and undesired effect
that occurs at normal drug doses
Excludes excessive dosages
Can range from annoying to life-threatening
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Adverse Drug Reactions
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Scope of the problem
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Severe reactions (potentially fatal)
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Mild reactions
• Drowsiness, nausea, itching, and rash
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
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Terms Related to Adverse
Drug Reactions
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Side effect
Toxicity
Allergic reaction
Idiosyncratic effect
Iatrogenic disease
Physical dependence
Carcinogenic effect
Teratogenic effect
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Terms Related to Adverse
Drug Reactions cont’d
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Organ-specific toxicity
Kidneys
Lungs
Inner ear
Heart
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QT interval
Liver
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Terms Related to Adverse
Drug Reactions
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Side effect
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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
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Formal definition: adverse drug reaction caused
by excessive dosing
May occur even with normal dosing
• Neutropenia (risk for infection) and anticancer
medications
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Terms Related to Adverse
Drug Reactions
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Allergic reaction
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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).
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Terms Related to Adverse
Drug Reactions
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Idiosyncratic effect
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An uncommon drug response resulting from a
genetic predisposition
Succinylcholine-induced paralysis
• Usually brief
• May last for hours in genetically predisposed patient
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Terms Related to Adverse
Drug Reactions
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Iatrogenic disease
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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
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Terms Related to Adverse
Drug Reactions
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Physical dependence
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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
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Important to warn patients against abrupt
discontinuation of any medication without first
consulting a knowledgeable health professional
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Terms Related to Adverse
Drug Reactions
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Carcinogenic effect
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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
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Drug-induced birth defect
More discussion of this topic in Chapter 9
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adverse Drug Reactions
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Organ-specific toxicity
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Many drugs are toxic to specific organs.
Common examples include
• Kidneys: amphotericin B (antifungal)
• Heart: doxorubicin (anticancer)
• Lungs: amiodarone (antidysrhythmic)
• Inner ear: aminoglycoside (antibiotic)
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Organ-Specific Toxicity
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Hepatotoxic drugs
QT interval drugs
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Hepatotoxic Drugs
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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:
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Jaundice, dark urine, light-colored stools, nausea, vomiting,
malaise, abdominal discomfort, loss of appetite
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QT Interval Drugs:
More Than 100 Are Known
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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
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Examples: torsades de pointes, V-fib
Minimizing the risk
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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.
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Identifying Adverse Drug Reactions
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Can be very difficult to determine whether a
specific drug is responsible for an observed
adverse event
Other factors to consider
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Underlying illness
Other drugs
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Identifying Adverse Drug Reactions
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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?
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adverse Reactions to New Drugs
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Ways to Minimize Adverse
Drug Reactions
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Responsibility for reducing ADRs lies with
everyone associated with drug production
and usage
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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.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Ways to Minimize Adverse
Drug Reactions
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Anticipation of ADRs can help minimize them.
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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
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Patients with chronic disorders are especially
vulnerable to ADRs.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Boxed Warnings
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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.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Medication Errors
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Major cause of morbidity and mortality
Documented in two landmark reports from the
Institute of Medicine:
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To Err Is Human—1999
Preventing Medication Errors—2006
It is estimated that medication errors
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Injure 1.5 million people per year
Kill 7000 people per year
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Medication Errors
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Defined by the National Coordinating Council
for Medication Error Reporting and
Prevention (NCCMERP) as
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“. . .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”
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Medication Errors
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Risk for error in hospitals is high because
each medication order is processed by
several people.
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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.
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Types of Medication Errors
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Fatal medication errors
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Overdose: 36.4%
Wrong drug: 16.2%
Wrong route: 9.5%
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Causes of Medication Errors
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90% of all errors are due to
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Human factors
Communication mistakes
Name confusion
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Ways to Reduce Medication Errors
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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.
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About 20 drugs cause 80% of medication errorrelated deaths.
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Ways to Reduce Medication Errors
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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.
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Ways to Report Medication Errors
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Medication Errors Reporting (MER) program
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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
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