Chapter 7 - Adverse Drug Reaction And Medication Errors

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

PROBLEM - drugs can adversely affect all body systems in varying degrees of OF THE

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, reexposure 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

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 TO

- 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

MEDICATION 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 OF

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

REDUCE 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 TO

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

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 TO