CHAPTER 7 ADVERSE DRUG REACTIONS & MEDICATION ERRORS

I. Adverse Drug Reactions (ADR)

- any noxious, unintended, and undesired effect that occurs at normal drug
doses, excludes undesired
effects that occur when dosage is excessive (defined by the World
Health Organization)
- can range in intensity from annoying to life threatening
- when drugs are used properly, many ADR can be avoided or at least kept
to a minimum

A. SCOPE OF THEPROBLEM
- drugs can adversely affect all body systems in varying degrees of
intensity
- mild reactions include drowsiness, nausea, itching, and rash
- severe reactions include respiratory depression, neutropenia (profound
loss of neutrophilic white blood
cells, hepatocellular injury, anaphylaxis, and hemorrhage – all of
which can result in death
- adverse effects are most common in the elderly and very young
- severe illness also increases the risk of an ADR
- adverse events are more common in patients receiving multiple drugs

B. DEFINITIONS

1. Side Effect – a nearly unavoidable secondary drug effect produced at

therapeutic doses
- intensity is dose dependent and generally predictable
- response can develop soon after the onset of the drug use or as
long as weeks or months
later
- ex. Antihistamines causing drowsiness

2. Toxicity – an adverse drug reaction caused by excessive dosing

- today the term has come to mean any severe ADR, regardless of
the dose that caused it
- anticancer drugs cause neutropenia putting patients at high risks of
infection even though the
dosage is therapeutic
- ex. Overdose of morphine causing a coma or severe hypoglycemia
from an overdose of
insulin

3. Allergic Reaction – an immune response

- once the immune system has been sensitized to a drug, re-
exposure to that drug can trigger
an allergic response
- intensity is largely independent of dosage
 - very few medications cause severe allergic reactions; in fact, the
most serious reactions are
caused by just one drug family -- penicillins
- reactions can range from mild itching to sever rash to anaphylaxis
- reactions are determined primarily by the degree of sensitization of
the immune system – not
by drug dosage

anaphylaxis – a life-threatening response characterized by

bronchospasm, laryngeal
edema, and a precipitous drop in blood pressure

4. Idiosyncratic Effect – an uncommon drug response resulting from a

genetic predisposition

5. Iatrogenic Disease – a disease produced by a physician

- derived from the Greek word iatros = physician and –genic = to
produce
- also used to denote a disease produced by drugs
- nearly identical to idiopathic (naturally occurring) diseases
- ex. Patients taking certain antipsychotic drugs may develop a
syndrome whose symptoms
closely resemble those of Parkinson’s disease

6. Physical Dependence – a state in which the body has adapted to

prolonged drug exposure in such a
way that an abstinence syndrome will result if drug use is
discontinued
- develops during long term use
- precise nature of the abstinence syndrome is determined by the
drug involved
- usually associated with “narcotics” (heroin, morphine, and other
opioids); however, these are
not the only dependence-inducing drugs
- patients should be warned against abrupt discontinuation of any
medication without first
consulting a knowledgeable health professional
- people heal better when not in pain – DO NOT WITHHOLD
MEDICATIONS DUE TO
PHYSICAL DEPENDENCY

7. Carcinogenic Effect – ability of certain medications and environmental

chemicals to cause cancers
- several drugs used to treat cancer are among the drugs with the
greatest carcinogenic
potential
- unlikely that carcinogenic potential will be detected during
preclinical and clinical drug trials
 - ex. Diethylstilbestrol (DES) – synthetic hormone with actions similar
to estrogen was at one
time used to prevent spontaneous abortion during high-risk
pregnancies. It wasn’t until
years later when vaginal and uterine cancers developed in
females who had been
exposed to this drug in utero.

8. Teratogenic Effect – a drug-induced birth defect

- capable of causing birth defects
- ex. Accutane for acne

C. ORGAN SPECIFIC TOXICITY

- many drugs are toxic to specific organs
- examples include: injury to the kidneys caused by amphotericin B
(antifungal drug)
injury to the heart caused by amiodarone
(antidysrhythmic drug)
injury to the inner ear caused by aminoglycoside
antibiotics (e.g., gentamicin)

1. Hepatotoxic Drugs
- drugs are the leading cause of acute liver (primary site of drug
metabolism) failure, a rare
condition that can rapidly prove fatal (most cases end with a
liver transplant or in
death)
- as some drugs undergo metabolism, they are converted to toxic
products that can injure liver
cells (most common reason for withdrawing drugs from the
market)
- signs of liver injury include jaundice (yellow skin and eyes), dark
urine, light-colored stools,
nausea, vomiting, malaise, abdominal discomfort, loss of
appetite
- patients taking hepatotoxic drugs should undergo liver function
tests (LFTs) at baseline and
periodically thereafter
- ex. Combination of acetaminophen (Tylenol, others) with alcohol

2. QT Interval Drugs – ability of some medications to prolong the QT

interval on the electrocardiogram,
thereby creating a risk of serious disrhythmias
- QT interval is a measure of the time required for the ventricles to
repolarize after each
contraction; when the interval is prolonged, patients can
develop dysrhythmia called
torsades de pointes which can lead to potentially fatal
ventricular fibrillation
 - FDA now requires that all new drugs be tested to see if they cause
QT prolongation
- elderly and patients with bradycardia, heart failure congenital QT
prolongation, and low levels
of potassium or magnesium, and women are at risk

D. IDENTIFYING ADVERSE DRUG REACTIONS

- it can be very difficult to determine whether a specific drug is responsible
of an observed adverse
event
- underlying illness and other drugs being taken could be the actual cause

Indicators:
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 reinstated?
Is the illness itself sufficient to explain the event?
Are other drugs in the regimen sufficient to explain the event?

- if the answers reveal a temporal relationship between the presence of

the drug and the adverse event,
and if the event can not be explained by the illness itself or by other
drugs in the regimen, then there is a highly probability that the drug
under suspicion is indeed the culprit
- this process is limited
- can only identify adverse effects that occur while the drug is being
used
- cannot identify adverse events that develop years after the drug
has been discontinued

E. WAYS TO MINIMIZE ADVERSE DRUG REACTIONS

- responsibility for reducing ADRs lies with everyone associated with drug
manufacture and use
- pharmaceutical industry must strive to produce the safest possible
medicines
- prescriber must select the least harmful medicine for a patient
- nurse must evaluate patients for ADRs
- patients and families must be educated in ways to avoid or
minimize harm
- knowledge will allow early identification of adverse effects
- liver, kidneys, and bone marrow are important sites of drug toxicity
- liver damage symptoms include jaundice, dark urine, light-colored
stools, nausea, vomiting,
malaise, abdominal discomfort, loss of appetite
- kidneys should undergo routine urinalysis and measurement of
serum creatinine
- bone marrow should have periodic blood cell counts
- physician must balance potential risks of one drug versus its probable
benefits
 - chronic disorders such as hypertension, epilepsy, heart disease and
psychoses require individualized
drug therapy
- anticipation is key

F. MEDICATION ERRORS
- EVERYONE MAKES MEDICATION ERRORS

medication error – 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

G. TYPES OFMEDICATION ERRORS

- some types of errors cause harm directly and some, indirectly
- among fatal medication errors, the most common types are giving an
overdose, followed by giving the
wrong drug, then using the wrong route

H. CAUSES OF MEDICATION ERRORS

- human factors, communication mistakes, name confusion, packaging and
labeling are among the fatal
medication errors
- of the human factors, performance deficits (e.g., administering a drug IV
instead of IM) are the most
common, followed by knowledge deficits, then miscalculation of
dosage
- potential for lethal confusion among trade names is a powerful reason for
abandoning them in favor of
universal use of generic names

I. WAYS TOREDUCE MEDICATION ERRORS

- a central theme in these efforts is to change institutional culture from
one that focuses on “naming,
shaming, and blaming” those who make mistakes to one focused on
designing institution wide
processes and systems that can prevent errors from happening

System of Reduction:
 Institutional Culture – establish an organizational commitment to a
culture of safety
- provide medication safety education for all professional
employees
- maintain ongoing recognition of safety innovation
- encourage identification of errors and develop new patient
safety systems
Infrastructure – designate a medication safety coordinator/officer
- promote greater use of clinical pharmacists in high-risk areas
- establish area-specific guidelines for unit-stocked
medications
- establish a mechanism to ensure availability of critical
medication information to all
members of patient’s care team
Clinical Practice – eliminate dangerous abbreviations and dose
designations
- implement safety checklists for high-alert medications and
infusion pumps
- develop limitations and safeguards regarding verbal orders
- perform failure-mode analysis during procurement process
- implement triggers and markers to indicate potential adverse
medication events
Technology – eliminate the use of infusion pumps that lack free-flow
protection
- prepare for implementation of computerized prescriber order
entry system

J. HOW TO REPORT A MEDICATION ERROR

- report a medication error via the Medication Errors Reporting (MER)
Program – a nationwide
program set up by the USP in cooperation with the Institute for Safe
Medical Practices (ISMP)
- all reporting is confidential and can be done by phone or fax or through
the internet
- objective is not to establish blame, but to improve patient safety by
increasing our knowledge of
medication errors