Introduction An adverse drug reaction (ADRs) is an unwanted, undesirable effect of a medication that occurs during usual clinical use. Adverse drug reactions occur almost daily in health care institutions and can adversely affect a patient’s quality of life, often causing considerable morbidity and mortality. Adverse drug reactions may cause patients to lose confidence in or have negative emotions toward their physicians and seek self-treatment options, which may consequently precipitate additional ADRs. Around 5% of all hospital admissions are the result of an ADR, and around 10%– 20% of inpatients will have at least one ADR during their hospital stay (Kongkaew 2008; Lundkvist 2004; Pirmohamed 1998). This article discusses methods of ADR detection and classification and associated treatment strategies. Defining ADRs The definition of an ADR is often confused with that of an adverse drug event (ADE). The World Health Organization (WHO) defines an ADE as “Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment” (WHO 2005). The WHO defines an ADR as “a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.” Classification of ADRs Adverse drug reactions were originally classified into two subtypes. Type A ADRs are dose-dependent and predictable; they are augmentations of known pharmacologic effects of the drug, such as orthostatic hypotension with antihypertensive medications. Type B ADRs are uncommon and unpredictable, depending on the known pharmacology of the drug; they are independent of dose and affect a small population, suggesting that individual patient host factors are important (Pirohamed 2003; Edwards 2000). Hypersensitivity (allergic) reactions to drugs are examples of type B ADRs. Type A reactions were later called augmented, and type B reactions, bizarre. Two further types of reactions were eventually added: chronic reactions, which relates to both dose and time (type C), and delayed reactions (type D). Withdrawal later became the fifth category (type E), and most recently, unexpected failure of therapy became the sixth (type F) (Rohilla 2013; Edwards 2000). Type of Reaction (Mnemonic) Features Examples Management A: Dose related (Augmented) Common Related to the pharmacologic action of the drug – exaggerated pharmacologic response Predictable Low mortality Dry mouth with tricyclic antidepressants, respiratory depression with opioids, bleeding with warfarin, serotonin syndrome with SSRIs, digoxin toxicity Reduce dose or withhold drug Consider effects of concomitant therapy B: Non–dose related (Bizarre) Uncommon Not related to the pharmacologic action of the drug Unpredictable High mortality Immunologic reactions: anaphylaxis to penicillin Idiosyncratic reactions: malignant hyperthermia with general anesthetics Withhold and avoid in future C: Dose related and time related (Chronic) Uncommon Related to the cumulative dose Hypothalamic-pituitary-adrenal axis suppression by corticosteroids, osteonecrosis of the jaw with bisphosphonates Reduce dose or withhold; withdrawal may have to be prolonged D: Time related (Delayed) Uncommon Usually dose related Occurs or becomes apparent sometime after use of the drug Carcinogenesis Tardive dyskinesia Teratogenesis Leucopenia with lomustine Often intractable E: Withdrawal (End of use) Uncommon Occurs soon after withdrawal of the drug Withdrawal syndrome with opiates or benzodiazepines (e.g., insomnia, anxiety) Reintroduce drug and withdraw slowly F: Unexpected failure of therapy (Failure) Common Dose related Often caused by drug interactions Inadequate dosage of an oral contraceptive when used with an enzyme inducer Resistance to antimicrobial agents Increase dosage Consider effects of concomitant therapy Populations at Greatest Risk Due To ADRs Pediatrics Adverse drug reactions are common in the pediatric population. Developmental changes affect the pharmacodynamics and pharmacokinetics of many of the drugs used in neonates, infants, and children. For example, gastric emptying is delayed in neonates and infants, resulting in longer absorption time and potentially increasing the risk of an ADR. The volume of distribution also differs, compared with adults, as does protein-binding capacity, phase I and II metabolic pathways, and glomerular filtrate rate. Therefore, extrapolation of pediatric dosages from adult dosages should be avoided (Fabiano 2012). Geriatrics The WHO defines elderly as individuals 60 years and older. The percentage of people in this age category continues to rise and the total is expected to reach 2 billion by 2050 (Brahma 2013). As the number of drugs increases, the risk of medication nonadherence also increases, further increasing the risk of an ADR. By examining the patient’s medication record and evaluating for duplicate therapies or medications being used to potentially treat ADRs caused by other medications, pharmacists can help reduce unnecessary prescribing and optimize the patient’s drug therapy regimen. Detecting and preventing ADRs in the older adult population remains a challenging, yet important part of good clinical practice. Tools available to assist in evaluating potentially inappropriate prescribing in older adults include the Beers Criteria, IPET (Improved Prescribing in the Elderly Tool), MAI (Medication Appropriateness Index), and STOPP (Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions) (Petrovic 2012). Renal and Hepatic Impairment Most drugs are metabolized by the liver and excreted by the kidneys. Impairment or failure of either of these organs can affect drug absorption, distribution, bioavailability, CYP metabolism, and clearance. Monitoring the laboratory values and adjusting the doses of drugs using these metabolic and excretory pathways can prevent an ADR. Special consideration should be given to identifying and, if possible, avoiding drugs that undergo extensive hepatic first-pass metabolism in patients with hepatic impairment. Pharmacovigilance can be used to assist prescribers with dosing or alternative drug selection in these patients. Conclusion As medication experts, pharmacists are a vital part of the treatment team, especially when an ADR occurs. Treating an ADR consists mainly of supportive therapy with symptom management. Furthermore, additional steps should be taken to determine the cause of the patient’s symptoms and whether they can be attributed to the use of a drug. Begin by evaluating the nature of the event. Thoroughly review the medical history available in the patient’s chart. Identify and document the clinical reaction, including the patient’s subjective report of symptoms. Review the patient’s medication list, and then
Warning! 10 Drugs That May Cause Memory Loss
Dementia is an overall term for diseases and conditions characterized by a decline in memory, language, problem-solving and other thinking skills that affect a person’s ability to perform everyday activities. Memory loss is an example. Alzheimer’s is the most common cause of dementia. Causes Of Dementia Dementia is caused by damage to brain cells. This damage interferes with the ability of brain cells to communicate with each other. When brain cells cannot communicate normally, thinking, behavior and feelings can be affected. The brain has many distinct regions, each of which is responsible for different functions (for example, memory, judgment, and movement). When cells in a particular region are damaged, that region cannot carry out its functions normally. Different types of dementia are associated with particular types of brain cell damage in particular regions of the brain. For example, in Alzheimer’s disease, high levels of certain proteins inside and outside brain cells make it hard for brain cells to stay healthy and to communicate with each other. The brain region called the hippocampus is the center of learning and memory in the brain, and the brain cells in this region are often the first to be damaged. That’s why memory loss is often one of the earliest symptoms of Alzheimer’s. While most changes in the brain that cause dementia are permanent and worsen over time, thinking and memory problems caused by the following conditions may improve when the condition is treated or addressed: Depression Medication side effects Excess use of alcohol Thyroid problems Vitamin deficiencies 10 Drugs That May Cause Memory Loss 1. Antianxiety drugs2. Cholesterol drugs3. Antiseizure drugs4. Antidepressant drugs5. Narcotic painkillers6. Parkinson’s drugs7. Hypertension drugs8. Sleeping aids9. Incontinence drugs10. Antihistamines 1. Antianxiety drugs (Benzodiazepines) Why they are prescribed: Benzodiazepines are used to treat a variety of anxiety disorders, agitation, delirium and muscle spasms, and to prevent seizures. Because benzodiazepines have a sedative effect, they are sometimes used to treat insomnia and the anxiety that can accompany depression. Examples: Alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium), flurazepam (Dalmane), lorazepam (Ativan), midazolam (Versed), quazepam (Doral), temazepam (Restoril) and triazolam (Halcion) 2. Cholesterol-lowering drugs (Statins) Why they are prescribed: Statins are used to treat high cholesterol. Examples: Atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor). How they can cause memory loss: Drugs that lower blood levels of cholesterol may impair memory and other mental processes by depleting brain levels of cholesterol as well. In the brain, these lipids are vital to the formation of connections between nerve cells — the links underlying memory and learning. (The brain, in fact, contains a quarter of the body’s cholesterol.) A study published in the journal Pharmacotherapy in 2009 found that three out of four people using these drugs experienced adverse cognitive effects “probably or definitely related to” the drug. The researchers also found that 90 percent of the patients who stopped statin therapy reported improvements in cognition, sometimes within days. In February 2012, the Food and Drug Administration ordered drug companies to add a new warning label about possible memory problems to the prescribing information for statins. Alternatives: If you’re among the many older Americans without known coronary disease who are taking these drugs to treat your slightly elevated LDL (“bad”) cholesterol and low HDL (“good”) cholesterol), ask your doctor or other health care provider about instead taking a combination of sublingual (under-the-tongue) vitamin B12 (1,000 mcg daily), folic acid (800 mcg daily) and vitamin B6 (200 mg daily). 3. Antiseizure drugs Why they are prescribed: Long used to treat seizures, these medications are increasingly prescribed for nerve pain, bipolar disorder, mood disorders, and mania. Examples: Acetazolamide (Diamox), carbamazepine (Tegretol), ezogabine (Potiga), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), rufinamide (Banzel), topiramate (Topamax), valproic acid (Depakote) and zonisamide (Zonegran). How they can cause memory loss: Anticonvulsants are believed to limit seizures by dampening the flow of signals within the central nervous system (CNS). All drugs that depress signaling in the CNS can cause memory loss. Alternatives: Many patients with seizures do well on phenytoin (Dilantin), which has little if any impact on memory. Many patients with chronic nerve pain find that venlafaxine (Effexor) — which also spares memory — alleviates their pain. 4. Antidepressant drugs (Tricyclic antidepressants) Why they are prescribed: TCAs are prescribed for depression and, increasingly, anxiety disorders, eating disorders, obsessive-compulsive disorder, chronic pain, smoking cessation and some hormone-mediated disorders, such as severe menstrual cramps and hot flashes. Examples: Amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil) and trimipramine (Surmontil). How they can cause memory loss: About 35 percent of adults taking TCAs report some degree of memory impairment and about 54 percent report having difficulty concentrating. TCAs are thought to cause memory problems by blocking the action of serotonin and norepinephrine — two of the brain’s key chemical messengers. Alternatives: Talk with your health care provider about whether nondrug therapies might work just as well or better for you than a drug. 5. Narcotic painkillers Why they are prescribed: Also called opioid analgesics, these medications are used to relieve moderate to severe chronic pain, such as the pain caused by rheumatoid arthritis. Examples: Fentanyl (Duragesic), hydrocodone (Norco, Vicodin), hydromorphone (Dilaudid, Exalgo), morphine (Astramorph, Avinza) and oxycodone (OxyContin, Percocet). These drugs come in many different forms, including tablets, solutions for injection, transdermal patches, and suppositories. How they can cause memory loss: These drugs work by stemming the flow of pain signals within the central nervous system and by blunting one’s emotional reaction to pain. Both these actions are mediated by chemical messengers that are also involved in many aspects of cognition. So the use of these drugs can interfere with long- and short-term memory, especially when used for extended periods of time. Alternatives: In patients under the age of 50 years, nonsteroidal anti-inflammatory drugs (NSAIDs) are the frontline therapy for pain. Unfortunately, NSAID therapy is less appropriate for older patients, who have a much higher risk of dangerous gastrointestinal bleeding. Research shows the risk goes up with the dosage and duration of treatment. 6. Parkinson’s drugs (Dopamine agonists) Why they are
Handling of LASA (Look-Alike Sound-Alike) Drugs
Look-Alike Sound-Alike (LASA) medications include medications that are visually the same in physical appearance or packaging and names of medications that have similar spelling or similar phonetics. As more medicines and new brands are being marketed in addition to the thousands already available, many of these medication names may look or sound alike. Confusing medication names and similar product packaging may lead to potentially harmful medication errors. The increasing potential for LASA medication errors was also highlighted in the Joint Commission’s Sentinel Event Alert. Emphasis on patient safety in the naming of medicines is now undertaken by national and international regulatory and advisory boards. The World Health Organisation’s International Non-proprietary Names Expert Group works to develop international non-proprietary names for pharmaceutical medicinal substances for acceptance worldwide. Healthcare organizations need to institute risk management strategies to minimize adverse events with LASA medications and enhance patient safety. To aid in this effort, this article on Handling of Look-Alike Sound-Alike Medications is published, it is hoped that errors relating to LASA medications can be minimized, if not eliminated, through identification and implementation of safety precautions. Common Risk Factors Common risk factors associated with LASA medications include: Illegible handwriting Incomplete knowledge of drug names Newly available products Same packaging or labeling Similar strengths, dosage forms, frequency of administration Similar clinical use Strategies To Avoid Errors Procurement Storage Prescribing Dispensing/Supply Administration Patient Education 1. Procurement (a) Minimize the availability of multiple medicine’s strengths. (b) Whenever possible, avoid the purchase of medicines with similar packaging and appearance. As new products or packages are introduced, compare them with existing packaging. 2. Storage (a) Use Tall Man lettering to emphasize differences in medications with sound-alike names. Tall Man lettering (or Tallman lettering) is the practice of writing part of a medicine name in upper case letters to help distinguish soundalike, look-alike medications from one another to avoid medication errors. Tall Man lettering involves highlighting the dissimilar letters in two names to aid in distinguishing between the two. The Institute for Safe Medication Practices (ISMP), U.S Food and Drug Administration (FDA), The Joint Commission and other safety-conscious organizations have promoted the use of Tall Man lettering as one means of reducing confusion between similar medication names. Examples of Tall Man lettering are metFORMIN and metoPROLOL. (b) Use additional warning labels for look-alike medicines. Warning labels should be uniform throughout the respective facility to facilitate identification. 3. Prescribing (a) Write legibly. Write clearly whether on an inpatient order or on a prescription. (b) The prescription should clearly specify the name of the medication, dosage form, dose and complete direction for use. (c) Include the diagnosis or medication’s indication for use. This information helps to differentiate possible choices in illegible orders. (d) Whenever possible, drug names in computerized prescriber order entry (CPOE) should incorporate Tall Man lettering. (e) Communicate clearly. Take your time in pronouncing the drug name whenever an oral order has to be made. Ask that the recipient of the oral communication repeat the medication name and dose. Verbal orders should be limited to emergency situations only. 4. Dispensing (a) Identify medicines based on their name and strength and not by its appearance or location. (b) Check the appropriateness of the dose for the medicines dispensed. (c) READ medication labels carefully at all dispensing stages and perform a triangle check. Triangle check is to check actual medicines against the medicines’ labels and against the prescription. (d) Double-checking should be conducted during the dispensing and supply process. (e) Highlight changes in medication appearances to patients upon dispensing. 5. Administration Read medication labels carefully during the administration process and perform a triangle check. Triangle check is to check medicine against the medication label and against the prescription. 6. Patient Education (a) Inform patients on changes in medication appearances. (b) Educate patients and their caregivers to alert healthcare providers whenever a medication appears to vary from what is usually taken or administered. (c) Encourage patients and their caregivers to learn the names of their medications. Table 1. FDA-Approved List of Generic Drug Names with Tall Man Letters