Pharmacy Drug Class Review

Transcription

1 Pharmacy Drug Class Review April 15, 2014 Authored By: Gina DeRue PharmD, CDE, BCACP Disclaimer: Specific agents may have variations Edited By: Richard J. Kraft, Pharm.D.BCPS ANTICHOLINERGIC BURDEN A focus on medication risk in older populations Background: Elderly populations and physical changes that lead to increased risks Common guidelines for managing medication use in the elderly o Beers Criteria o STOPP Criteria Rating Scales for Medications with Known Anticholinergic Burden o Anticholinergic Cognitive Burden List o Anticholinergic Risk Scale Recommended Alternative For Common Anticholinergic Medications Patient Cases References Highlights: The Quick Read Information 1. Older adults are times more likely to be hospitalized after experiencing an adverse drug related event that brings them to the ER. a. two b. three c. five d. seven 2. What percentage of adverse drug-related events are preventable? a. 10% b. 25% c. 40% d. 15% 3. The Beers Criteria identifies potentially inappropriate medications (PIMs) with a focus on a. Preventing inappropriate medication use in certain conditions to avoid adverse drug related events b. Preventing the use of anticholinergic agents, specifically, to prevent adverse drug related events c. Preventing expensive medication use in older adults d. Preventing complex medication regimens in older adults 4. The Anticholinergic Burden Scale identifies potentially inappropriate medications (PIMs) with a focus on a. Preventing inappropriate medication use in certain conditions to avoid adverse drug related events b. Preventing the use of anticholinergic agents, specifically, to prevent adverse drug related events c. Preventing expensive medication use in older adults d. Preventing complex medication regimens in older adults 5. Risk of cognitive impairment is increased by nearly 50% after 6 years once a drug s ACB score is what number? Introduction: a. 1 Summary b. of 2 Changes c. from JNC-7 to J 6. Which ARS score is associated with more anticholinergic burden? a. 1 b. 2 c. 3 QUIZ ANSWERS

2 Background It is well-established in current literature that potentially inappropriate medications (PIMs) represent a danger to older adults. However, such medications continue to be utilized as first-line treatments for this vulnerable population, despite evidence of poor outcomes related to use 1. Research has suggested patients utilizing PIMs experience an increase in adverse drug-related events, hospitalization and overall mortality. Older adults ( 65 years) are twice as likely to as others to come to the emergency department for adverse drug events (ADEs) (over 177,000 emergency visits annually) and nearly 7 times more likely to be hospitalized after an emergency visit 2. An estimated 40% of all adverse drug-event related visits are thought to be preventable. Elderly patients often experience significant physical changes that account for their enhanced sensitivity to PIMs. Specifically, these patients experience age-related decreases in glomerular filtration and in body composition that affect the pharmacodynamics and pharmacokinetics of many agents 3. Elderly patients also commonly take multiple agents to manage polycomorbidities, which increases the potential for significant drugdrug interactions. Some of the more significant changes in older adults are the cognitive changes that can be noticed with aging. Drugs that affect cortical brain function through alterations in acetylcholine levels, such as those with anticholinergic activity, may cause significant cognitive impairment in the elderly 3. Anticholinergic (ACh) drugs competitively inhibit binding of the neurotransmitter acetylcholine to muscarinic acetylcholine receptors. Muscarinic receptors are found on peripheral postganglionic cholinergic nerves in smooth muscle (intestinal, bronchial, and cardiac), the secretory glands (salivary and sweat), the ciliary body of the eye, and the central nervous system (CNS) 12. Effects of ACh agents can be divided into 2 categories: central vs peripheral. In addition to cognitive impairment,a central effect, ACh medications may contribute to other central adverse effects such as: falls, delirium or hallucination. Peripheral effects include dry mouth, blurred vision, constipation or urinary retention, nausea, impaired sweat response and tachycardia 4,5. While both central and peripheral effects of anticholinergics are concerning and responsible for significant patient morbidity, the tendency for centrally acting anticholinergics to cause delirium is of the utmost concern as delirium has been associated with mortality rates as high as 40% 11. While central and peripheral effects are commonly seen together, central effects may persist after resolution of peripheral symptoms 12. In a 2011 study conducted by Fox et al, ACh medication use has been associated with increased mortality over a 2 year period after adjustment for multiple comorbid conditions. See also: anticholinergic toxicity. Unfortunately, many ADEs experienced by patients warrant treatment with additional agents to mitigate these unpleasant and often dangerous effects. This leads to cyclic prescribing patterns known as prescribing cascades that can significantly impact the cost of care. For example, patients with sudden depressive symptoms could be prescribed amitriptyline. Amitriptyline might unknowingly to the prescriber induce confusion if the patient fails to recognize or report this new symptom. The patient may be prescribed treatment such as donepezil to help with confusion. The patient might then experience restlessness and trouble sleeping, upon which they could receive a prescription for zolpidem. Due to the financial burden and health consequences experienced by the elderly each year, multiple guidelines have been implemented to help manage medication use in this population. Key Points: Older patients who take ACh drugs may experience ADEs that can increase morbidity and health costs Central ADEs include delirium (which is associated with up to 40% mortality rate), cognitive impairment, falls and hallucination Peripheral ADEs include dry mouth, blurry vision, constipation, urinary retention, nausea, impaired sweating and tachycardia ACh medication use has been associated with mortality over a 2-year period as high as 68% in heavy users Older adults are 7 times more likely to be hospitalized with ADEs after an ER visit

3 Guidelines for Medication Use in the Elderly Two specific guidelines have been introduced previously to help identify potentially inappropriate medications correlated with general ADEs in older adults. These guidelines include the Beers Criteria and the STOPP (Screening Tool of Older Person s Prescriptions) Criteria. These guidelines focus on preventing many ADEs, including but not limited to those induced by anticholinergic agents. A brief overview of these two guidelines is provided below: Beers Criteria The Beers Criteria was most recently updated in 2012 and identifies 53 medications in 3 categories 1 : 1) Medications to always avoid Examples include: glyburide, sliding scale insulin and megestrol 2) Medications that are potentially inappropriate in older adults with particular health conditions Examples include: selective serotonin reuptake inhibitors (SSRIs) in patients with history of falls and fractures, NSAIDs in patients with heart failure and urinary antimuscarinics such as trospium in patients with chronic constipation. 3) Medications to use with caution examples include aspirin in adults age 80, prasugrel (Effient ) in adults age 75 and dabigatran (Pradaxa ) in adults age 75 and/or with CrCl < 30 ml/min. STOPP Criteria STOPP is comprised of 65 clinically significant criteria for potentially inappropriate prescribing in older people. STOPP focuses on inappropriate combinations of medications with specific disease states. Each criterion is accompanied by a concise explanation as to why the prescribing practice is potentially inappropriate 6. It also has a counterpart, the START (Screening Tool to Alert doctors to the Right Treatment) criteria, which recommends medications for given conditions. Anticholinergic Medication Rating Scales Other tools focus specifically on anticholinergic medications, often rating medications based on how anticholinergic the agent is expected to be. The two scales that appear to be most commonly used are the Anticholinergic Cognitive Burden List (ACB) and the Anticholinergic Risk Scale (ARS). The anticholinergic cognitive burden list and anticholinergic rating scales are very similar to one another. The meaning of the scoring has variation between the scales although both measure along a 3-point scale. Of note, both lists may not necessarily encompass all anticholinergic agents that exist but rather those that were studied during the creation of these rating scales. Medications and ratings within each scale may also vary. These tools can be utilized to specifically identify high risk anticholinergic medications in an effort to avoid use in the older population. One scale is not necessarily preferred over the other. Anticholinergic Cognitive Burden (ACB) List The ACB is a list based on expert opinion from the Aging Brain Program (Indiana University) and literature review. This tool identifies prescription and over the counter medications and classifies them by the severity of their anticholinergic effects on cognition 8. The ABC ranks drugs as a 1 (possible), 2 (definite), or 3 (definite). Drugs ranked as at least a 2 on this scale increase the risk of cognitive impairment by as much as 46% over a period of six years 7,8. The list also specifies drugs in a "possible anticholinergic" category to increase physician awareness. For each one-point increase in ACB total score, there has been a correlation with a 26% increase in the risk of death and decline in mini mental status exam score by 0.33 points over 2 years. Some of the agents on the ACB list include less obvious offenders such as common antihistamines. Many agents on the list are commonly prescribed for age-related issues such as bladder incontinence, which can complicate prescribing.

4 Table 1: Anticholinergic Cognitive Burden (ACB) List Possible Anticholinergics Definite Anticholinergics ACB Score of 1 ACB Score of 2 ACB Score of 3 Alverine (Spasmonal ) Alprazolam (Xanax ) Atenolol (Tenormin ) Bupropion (Wellbutrin, Zyban ) Captopril (Capoten ) Chlorthaldione (Diuril, Hygroton ) Cimetidine (Tagamet ) Clorazepate (Tranxene ) Codeine (Contin ) Colchicine (Colcrys ) Diazepam (Valium ) Digoxin (Lanoxin ) Dipyridamole (Persantine ) Fentanyl (Duragesic, Actiq ) Furosemide (Lasix ) Fluvoxamine (Luvox ) Haloperidol (Haldol ) Hydralazine (Apresoline ) Hydrocortisone (Cortef, Cortaid ) Isosorbide (Isordil, Ismo ) Loperamide (Imodium ) Metoprolol (Lopressor, Toprol ) Morphine (MS Contin, Avinza ) Nifedipine (Procardia, Adalat ) Prednsione (Deltasone, Sterapred ) Quinidine (Quinaglute ) Ranitidine (Zantac ) Risperidone (Risperdal ) Theophylline (Theodur, Uniphyl ) Trazodone (Desyrel ) Triametere (Dyrenium ) Warfarin (Coumadin ) Amantadine (Symmetrel ) Belladonna (multiple) Carbamazepine (Tegretol ) Cyclobenzaprine (Flexeril ) Cyproheptadine (Periactin ) Loxapine (Loxitane ) Meperidine (Demerol ) Methotrimeprazine (Levoprome ) Molindone (Moban ) Oxcarbazepine (Trileptal ) Pimozide (Orap ) Amitriptyline (Elavil ) Amoxapine (Asentin ) Atropine (Sal-Tropine ) Benztropine (Cogentin ) Brompheniramine (Dimetapp ) Carbinoxamine (Histex, Carbihist ) Chlorphreniramine (Chlortrimeton ) Chlorpromazine (Thorazine ) Clemastine (Tavist ) Clomipramine (Anafranil ) Clozapine (Clozaril ) Darifenacin (Enablex ) Despiramine (Norpramin ) Dicyclomine (Bentyl ) Dimenhydrinate (Dramamine, others) Diphenhydramine (Benadryl, others) Doxepin (Sinequan ) Flavoxate (Urispas ) Hydroxyzine (Atarax, Vistaril ) Hyoscyamine (Anaspaz, Levsin ) Imipramine (Tofranil ) Meclizine (Antivert ) Methocarbamol (Robaxin ) Nortriptyline (Pamelor ) Olanzapine (Zyprexa ) Orphenadrine (Norflex ) Oxybutynin (Ditropan ) Paroxetine (Paxil ) Perphenazine (Trilafon ) Promethazine (Phenergan ) Propantheline (Pro-Banthine ) Quetiapine (Seroquel ) Scopolamine (Transderm Scop ) Thioridazine (Mellaril ) Tolterodine (Detrol ) Trifluoperazine (Stelazine ) Trihexyphenidyl (Artane ) Trimipramine (Surmontil ) Scoring Interpretation: Each definite ACh (score 2) may increase the risk of cognitive impairment by 46% over 6 years For each 1-point increase in the ACB score, a decline in MMSE of 0.33 points over 2 years has been suggested Each 1-point increase in the ACB total score has been correlated with a 26% increase in the risk of death. Do not reproduce without permission. Contact acb@agingbraincare.org

5 Anticholinergic Risk Scale (ARS) The ARS was developed in 2008 based on retrospective medical record review and expert opinion. It represents a ranked categorical list of commonly prescribed medications with central and peripheral anticholinergic potential based on serum anticholinergic activity. Medications are ranked on a 3-point scale. Scores of 0 represent low-no risk whereas scores of 3 represent high anticholinergic (ACh) potential. For an individual patient, the score is the sum of points for his or her number of medications Low or No ACh potential Very High ACh Potential ARS Study Highlights: Compared a geriatric evaluation and management cohort (GEM) with a primary care cohort A single medication with an ARS score of 3 was considered likely to cause at least 2 anticholinergic adverse events in more than 70%of the patients in the study cohorts. In the GEM cohort but NOT the primary care cohort, higher ARS scores were associated with increased risk of central effects In the primary care patients, higher ARS scores were associated with an adjusted risk for peripheral adverse events Table 2: The Anticholinergic Risk Scale (ARS) 5 1 Point Medications 2 point Medications 3 point Medications Carbidopa-Levodopa (Sinemet ) Entacapone (Comtan ) Haloperidol (Haldol ) Methocarbamol (Robaxin ) metoclopramide HCl (Reglan ) Mirtazapine (Remeron ) Paroxetine HCl (Paxil, Paxil CR ) Pramipexole Dihydrochloride (Mirapex, Mirapex ER ) Quetiapine fumarate (Seroquel, Seroquel XR ) Ranitidine HCl (Zantac ) risperidone (Risperdal ) Selegiline HCl (Emsam, Zelapar ) Trazodone HCl (Oleptro ) Ziprasidone HCl (Geodon ) Amantadine HCl (Symmetrel ) Baclofen Cetirizine HCl (Zyrtec, OTC) Cimetidine (Tagamet, OTC) Clozapine (Clozaril ) Cyclobenzaprine HCl (Flexeril ) Despiramine HCl (Norpramin ) Loperamide HCl (Immodium AD, OTC) Loratadine (Claritin, OTC) Nortriptyline HCl (Pamelor ) Olanzapine (Zyprexa ) Prochlorperazine maleate (Compazine ) Pseudoephedrine (Sudafed, OTC) Tolterodine tartrate (Detrol, Detrol LA ) Amitriptyline HCl (Elavil ) Atropine Benztropine mesylate (Cogentin ) Carisoprodol (Soma ) Chlorpheniramine maleate (Chlor-Trimeton Allergy, OTC) Chlorpromazine HCl (Thorazine ) Cyproheptadine HCl Dicyclomine HCl (Bentyl ) Diphenhydramine HCl (Benadryl ) Fluphenazine HCl Hydroxyzine HCl (Atarax ) Hydroxyzine pamoate (Vistaril ) Hyoscamine (Levbid ) Imipramine HCl (Tofranil ) Meclizine HCl (Dramamine, OTC) Oxybutynin chloride (Ditropan XL, Gelnique, Oxytrol ) Perphenazine

6 Promethazine HCl (Phenergan ) Thioridazine HCl (Mellaril Thiothixene Tizanidine HCl (Zanaflex ) Trifluoperazine HCl To calculate the ARS score for each patient, identify medications the patient is taking and add the total points for each medication. A single medication with an ARS score of 3 was considered likely to cause at least 2 anticholinergic adverse events in > 70% of older adults Note: this chart does NOT contain all anticholinergic medications; only those that were available with a given point score at the time of publication. Key Points: The Beers Criteria and STOPP Criteria focus broadly on PIM use for many drugs and disease states to avoid ADEs The ACB Scale and ARS focus specifically on anticholinergic agents and rank individual drugs based on the anticipated anticholinergic potential ACB focuses on central effects only; specifically on cognition ARS focuses on central AND peripheral effects ACB ranks drugs 1-3. Drugs with an ACB score of 2 increase the risk of cognitive impairment by almost 50% over the course of 6 years. For each 1-point increase in the ACB score, a decline in MMSE of 0.33 points over 2 years has been suggested Each 1-point increase in the ACB total score has been correlated with a 26% increase in the risk of death ARS Ranks drugs 0-3, with 3 having the most anticholinergic potential A single medication with an ARS score of 3 is likely to cause at least 2 anticholinergic ADEs in more than 70%of the patients based on RCT evidence Alternative Suggestions for Common Anticholinergics General strategies for avoiding anticholinergic ADEs include using agents with the lowest anticholinergic potential, and/or using medications at the lowest dose for the shortest amount of time necessary. Agents that rank a 2 or 3 on the ARS may be replaced with agents that only rank a 1. However, recall that even agents with low ranking can create an anticholinergic burden when used in combination with other anticholinergic agents. The START Criteria is a comprehensive guide recommending alternative agents that may be safer in older individuals. This would be a great reference point to start with for any drug that could affect the older population. START Criteria summary has been put together in a comprehensive chart in a September 2011 issue of Pharmacist s Letter 10. The criteria do outline specific anticholinergic medications that act centrally and also have recommendations for peripherally acting medications with anticholinergic properties. The recommendations are specific to specific conditions that accompany older age and may pertain to ambulatory or acute care situations. Please see: Table 3. An interdisciplinary team at the Aging Brain Program (creators of the ACB List) have put forth some clinical recommendations for alternatives to the definite anticholinergics (scores of 2 and 3). The recommendations are NOT meant to supersede clinical judgment and are intended to assist clinicians in practicing in acute patient care settings who provide care for patients with cognitive impairment such as dementia, mild cognitive

7 impairment or delirium. Please see: Table 4. Table 3: START/STOPP Criteria Alternative Recommendations 10 Drug/Class Central Nervous System Anticholinergics Anticholinergics Potentially Inappropriate Use in Elderly ( 65) per STOPP Criteria To treat neuroleptic EPS Bladder antispasmodics + dementia, chronic constipation, BPH or glaucoma Therapeutic Alternative EPS: decrease antipsychotic dose or change to atypical antipsychotic Constipation: fiber, fluids, stool softener (docusate), Miralax BPH: finasteride, dutasteride Antihistamines 1 st gen. Chlorpheniramine diphenhydramine promethazine Benzodiazepines Promethazine Tricyclic Antidepressants Use for more than 1 week With 1 or more falls in past 3 months With 1 or more falls in past 3 months Use of long-acting agent greater than 1 month With 1 or more falls in past 3 months With epilepsy Use > 1 week as antihistamine As hypnotic > 30 days With Parkinsonism > 30 days With dementia, glaucoma, arrhythmia, constipation, opioids, calcium channel blockers, urinary retention, BPH Cetirizine (Zyrtec), fexofenadine (Allegra), loratadine (Claritin), desloratadine (Clarinex), levoceterizine (Xyzal) Anxiety: short acting BZPs appropriately dosed alprazolam, lorazepam, oxazepam; buspirone, SSRI or SNRI Sleep: non-drug therapy; temazepam 7.5 mg, ramelteon 8 mg, zolpidem 5 mg (6.25 mg CR), zaleplon 5 mg, eszopiclone 1 mg for difficulty falling asleep/2 mg for difficulty staying asleep [Avoid chronic use] Nausea: Ondansetron (Zofran), granisetron (Kytril), dolasetron (Anzimet) Sleep: as above. Depression: SSRI (avoid fluoxetine), bupropion (cardiac patient), mirtazapine (insomnia or anorexia) Neuropathic pain: topical lidocaine, capsaicin Peripheral-Acting Anticholinergics Antispasmodics (Dicyclomine) Antidiarrheals Loperamide Diphenoxylate Metoclopramide Prochlorperazine Urinary antispasmodics With chronic constipation For diarrhea, unknown etiology Severe gastroenteritis With parkinsonism With dementia, glaucoma, chronic constipation, BPH Constipation: as above Aluminum hydroxide, cholestyramine, dietary changes Nausea: as above Urge incontinence: behavior therapy BPH: as above

8 Table 4: Recommended Alternatives for Medications with ACB List Definite Potential (Scores of 2) 8 Class ACB Drugs Alternatives 1 st Generation Antihistamines Brompheniramine Carboxinamine Chlorpheniramine Clemastine Diphenhydramine Dimenhydrinate Allergies/Itching: loratadine or cetirizine PO Insomnia: trazodone PO Antidepressants *Clinical judgment to consider if taper warranted Antipsychotics *Recommendations do NOT apply to chronic use for psychiatric diagnosis Central Anticholinergics Bladder Antispasmodics GI Antispasmodics Antiemetics Skeletal Muscle Relaxants Hydroxyzine Amitriptyline Amoxapine Clomipramine Desipramine Doxepin Imipramine Nortriptyline Paroxetine Trimipramine Chlorpromazine Clozapine Olanzapine Perphenazine Quetiapine Thioridazine Trifluoperazine Amantadine Benztropine Trihexyphenidyl Orphenadrine Darifenacin Flavoxate Oxybutynin Propantheline Tolterodine Atropine Dicyclomine Hyoscyamine Propantheline Hydroxyzine Meclizine Promethazine Scopolamine Cyclobenzaprine Methcarbamol Depression: sertraline or citalopram* PO Note: *doses > 20 mg/day not recommended Neuropathic pain: gabapentin PO Insomnia: trazodone PO Acute care: haloperidol PO or IM for 72 hours ONLY Movement disorders: dopamine agonists or levodopa Hold during acute care stay; consider scheduled toileting Reflux disorders: Esomeprazole orally Painful abdominal cramps: morphine orally or IV Consider ondansetron IV or PO, or metoclopramide PO Acetaminophen or oxycodone/acetaminophen Analgesics Meperidine Morphine Sulfate IV or PO Antiepileptics Carbamazepine Oxcarbazepine Do not reproduce without permission. Contact acb@agingbraincare.org Seizures: consult neuro Neuropathic pain: gabapentin or levetiracetam PO Mood disorders: consult psychiatry

9 Key Points: Manage anticholinergic burden by putting patients on agents with lower anticholinergic potential (i.e. drugs that are not on the list or that rank a 1 instead of a 3) Using multiple drugs with any sort of anticholinergic potential, even if low, creates an anticholinergic burden that can lead to unintended ADEs Use the lowest dose necessary for the shortest duration of time necessary Refer to the START criteria for managing general ADEs beyond anticholinergic effects Anticholinergic Toxicity Another term for a patient who carries a significant anticholinergic burden and therefore experiences adverse events is how much ACh toxicity the patient is exposed to. Patients can essentially experience ACh poisoning from the myriad of anticholinergic compounds that exist. Clinical presentation can be remembered in the mneumonic as follows: Table 6: Common Signs of Anticholinergic Toxicity / Overdose 12 Description Red as a beet" "Dry as a bone "Hot as a hare" "Blind as a bat" "Mad as a hatter" "Full as a flask" Physical Reaction due to Anticholinergic Toxicity Cutaneous vasodilation Anhidrosis Anhydrotic hyperthermia Nonreactive mydriasis Delirium; Hallucinations Hallucinations are often described as "Alice in Wonderland-like" or "Lilliputian type," where people appear to become larger and smaller. Patients with altered mental status often present with agitation and may appear to grab invisible objects from the air Urinary Retention Case Studies 9 NOTE: Other clinical features not included in the above mnemonic include tachycardia, which is the earliest and most reliable sign of anticholinergic toxicity, and decreased or absent bowel sounds.

10 Case 1: JB JB is a 70-year-old man with a medical history of hypertension, diabetes with neuropathy, and depression. He is using the following medications: ramipril 5 mg orally once daily amlodipine 5 mg orally once daily metformin 500 mg orally twice daily lidocaine 5% transdermal patch applied once daily for 18 hours amitriptyline 50 mg orally once daily vitamin E 400 IU orally once daily He comes to your office complaining of difficulty urinating and dry mouth that affects his appetite and speech. Your review of his medication regimen reveals that JB has also been taking diphenhydramine 25 mg orally at bedtime, three to four times per week, for the past three weeks due to difficulty falling asleep, and he has been taking his amitriptyline in the morning rather than at bedtime. 1) Using the ARS, how could you measure the anticholinergic burden for JB? 2) How could you reduce the anticholinergic burden for JB?

11 Case 2: SM SM is an 83 year old Caucasian female with a medical history significant for overactive bladder, type 2 diabetes, hypothyroidism, hypertension and depression. She notes a penicillin allergy that causes a rash and stomach upset with metformin. Her current medications include: Glyburide 5 mg 1 tablet twice daily Ditropan XL 10 mg 1 tablet daily Levothyroxine 75 mcg 1 tablet daily Lexapro 10 mg 1 tablet daily Diovan 320 mg 1 tablet daily Metoprolol tartrate 50 mg twice daily Hydralazine 50 mg 1 tablet three times daily Claritin 10 mg 1 tablet daily as needed for allergies Aspirin 81 mg 1 tablet daily for heart health At her annual visit, SM reports constipation and continued depression symptoms including difficulty sleeping and poor memory despite increasing her dose of Lexapro 2 weeks ago. She has been using stool softeners over the counter to help with the constipation. The prescriber decides to put her on amitriptyline 50mg QHS to help manage her depression symptoms and to help her sleep better. SM is admitted 4 weeks later to the ER with confusion and a fall. She unfortunately sustains a hip fracture and is given Demerol for pain. While at the hospital, the patient also complains of nausea, for which she is given Reglan 10 mg TID PRN nausea. The doctors place her on GI prophylaxis with Zantac. 1) Using the ACB, please identify the drugs with ACB Scores of: 1; 2; and 3. 2) Using the ARS, how could you measure the anticholinergic burden for SM? 3) What are the potentially unnecessary medications that may be the result of a prescribing cascade? 4) How could the patient s medications have been adjusted initially at her annual visit to address her concerns while minimizing the risk for adverse events? [Case Answers]

12 Quiz Answers 1. d 2. c 3. a 4. b 5. b 6. c Case Answers/Discussion: Case 1: JB 9 1) Using the ARS, how could you measure the ACh burden for J. B.? Add the ARS ratings assigned to each of the medications J. B. is using as follows: 0 (ramipril) + 0 (amlodipine) + 0 (metformin) + 0 (lidocaine) + 3 (amitriptyline) + 0 (vitamin E) + 3 (diphenhydramine). Based on the ARS ratings, the ACh burden for J. B. is 6. 2) How could you reduce the ACh burden for J. B.? Use an alternative antidepressant such as a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitor (SNRI) to treat his depression. You could switch amitriptyline to an SNRI such as duloxetine, which is effective for both depression and diabetic neuropathy. To further reduce the ACh burden, use an alternative to treat his insomnia. You could switch diphenhydramine to a nonpharmacologic intervention, a nonbenzodiazepine sedative-hypnotic such as zolpidem, or a combination thereof. You could also stop diphenhydramine and reassess his insomnia after switching amitriptyline to duloxetine to determine whether an alternative to diphenhydramine is still necessary. Case 2: SM 1) Using the ACB, please identify the drugs with ACB Scores of: 1; 2; and 3. Not on chart: glyburide, levothyroxine, lexapro, Diovan, Claritin, aspirin 1 hydralazine, metoprolol, Zantac (ranitidine) 2 Demerol 3 Amitriptyline, Ditropan (oxybutynin) 2) Using the ARS, how could you measure the anticholinergic burden for SM? By the time SM is hospitalized and receiving treatment, her score is 10. She has 2 medications with an ARS Score of 3, each of which can lead to 2 adverse events. Her score is: 0 (glyburide) + 3 (oxybutynin (Ditropan )) + 0 (levothyroxine) + 0 (Lexapro ) + 0 (Diovan ) + 0 (metoprolol tartrate) + 0 (hydralazine) + 2 (loratadine (Claritin )) + 0 (aspirin) + 3 (amitriptyline) (Demerol ) + 1 (Reglan (metoclopramide)), + 1(ranitidine (Zantac )). 3) What are the potentially unnecessary medications that may be the result of a prescribing cascade? Constipation and stool softener use can be the result of having Ditropan on board for her OAB, which can be managed at a lower dose or with behavioral therapy. After starting the patient on amitriptyline, she had a fall which probably resulted in the need for her Demerol, Reglan and Zantac.

13 4) How could the patient s medications have been adjusted initially at her annual visit to address her concerns while minimizing the risk for adverse events? a. Ditropan: The prescriber could have identified that Ditropan might not have been the greatest medication choice due to its rating of a 3 on either scale. Detrol has a slightly lower ARS rating so that could have been adjusted. b. Amitriptyline: When the patient complained of worsening depression, the prescriber could have noted that dose adjustments to SSRIs and SNRI s can take upwards of 6-8 weeks to observe effects before he added another agent. Trazodone also has a lower ARS score compared to amitriptyline and could have been used to jointly manage depression and insomnia. References: 1. American Society of Geriatrics. Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Available at: mmendations/2012. Accessed 30 March CDC. Adults and Older Adults Adverse Drug Events. Available from: Accessed 30 March Hastings GE. Drugs in the Elderly. University at Kansas Medical Center, Available from: Accessed 30 March Barclay L. New risk score predicts risk for anticholinergic adverse effects. Medscape Available from: Accessed 30 March Rochon PA. Drug prescribing for older adults. UpToDate. Wolters Kluwer Health, Inc. Available at: Accessed 30 March Gallagher P, Ryan C, Byrne S, Kennedy J, O'Mahony D. STOPP (Screening Tool of Older Persons' Prescriptions) and START (Screening Tool to Alert Doctors to Right Treatment): Consensus Validation. Int J Clin Pharmacol Ther. 2008;46: PL Detail-Document, Drugs with Anticholinergic Activity. Pharmacist s Letter/Prescriber s Letter. December Aging Brain Care. Anticholinergic Cognitive Burden List. Accessed 30 March Available from: Accessed 30 March Bain KT. Anticholinergic burden tracking adverse events. Aging Well; 4(2):8. Accessed 3 April Available from: PL Detail document, STARTing and STOPPing medications in the elderly. Pharmacists Letter/Prescribers Letter. September Tune LE. Anticholinergic effects of medication in elderly patients. J Clin Psychiatry 2001;62 (suppl 21). 12. Su M et al. Anticholinergic Poisoning. UpToDate. Wolters Kluwer Health Inc. Available at: Accessed 10 April 2014.