Side Effects and Interactions of Common Medications in Primary Care

Educational Objectives

The goal of this program is to prevent adverse outcomes associated with common medications. After hearing and assimilating this program, the clinician will be better able to:

1. Choose appropriate medications for elderly patients.

2. Counsel patients about potential drug interactions with herbal supplements.

3. Evaluate the association between angiotensin-converting enzyme inhibitors and serum creatinine levels.

Summary

Introduction: drug-related issues more common and more problematic in elderly than in nonelderly; 2011 study — used National Electronic Injury Surveillance System data to look at hospital visits for drug-related issues; ≈100,000 hospitalizations recorded over 2 yr of study; most hospitalizations occurred among individuals ≥80 yr of age; two-thirds of hospitalizations related to unintentional overdose; medications responsible for most hospitalizations included 1) warfarin (Coumadin), 2) insulin, 3) oral hypoglycemic agents, 4) oral antiplatelet agents, and 5) digoxin; 3 of these medications not included in Beers criteria

Beers criteria: 2012 iteration lists 53 medications or medication classes to avoid; 3 classes include medications to avoid due to side-effect profile, medications to avoid in older adults with specific diseases, and medications to be used with caution in older adults (ie, risks may outweigh benefits); criteria mostly evidence based; among Beers medication classes, anticholinergics and sedatives most problematic in elderly; 53-item list may be cumbersome to use in practice

Drug burden index: simplified for everyday use; assigns number from 1 to 3 based on degree of burden (with 3 indicating highest burden); takes into account anticholinergic and sedative burden of medications, cumulative exposure to these medications, and impact on physical and mental functioning; also takes into account minimum recommended daily dose

Anticholinergics and sedatives: anticholinergic effects of medications — include precipitation of acute angle-closure glaucoma, urinary retention, nausea, vomiting, decline in cognitive functioning, dry mouth, and tachycardia; drugs with anticholinergic effects — include tricyclic antidepressants (anticholinergic burden of 3), furosemide (Lasix), and nifedipine; drugs with anticholinergic and sedating effects — include first-generation antihistamines (but not second-generation antihistamines); drugs with sedating effects — include zolpidem (Ambien); eszopiclone (Lunesta) recommended over zolpidem and chemically related to zolpidem; eszopiclone approved for daily use, whereas zolpidem should be used no more than 3 times/wk and for no longer than 2 wk

Other high-risk medications: include warfarin and insulin; oral hypoglycemic agents — metformin not recommended in patients >80 yr of age due to increased risk for lactic acidosis; exercise caution when prescribing sulfonylureas; oral antiplatelet agents — monitor to ensure that appropriate doses taken; antihypertensive agents — avoid atenolol, which has anticholinergic effect

Recommendations: avoid polypharmacy (ie, >5 medications); consider new symptoms in elderly patients as possibly drug related; avoid cascades (ie, prescribing new medication to treat side effect of existing medication, in turn leading to additional side effects); adjust medications for renal insufficiency; attempt nondrug approaches

Herbal medicine: ≤75% of elderly use complementary and alternative medicine (CAM); CAM use highest in most educated and wealthiest individuals; less regulated than prescription medication; survey — 60% of respondents did not inform their physician about use of herbal supplements (main reason being physician’s failure to ask); 88% believed that manufacturer should provide safety information; 60% unaware that herbal preparations not well regulated

Sympathomimetic agents: ephedra — banned in 2004; increases metabolic rate; used in weight-loss products; bitter orange — replaced ephedra in weight-loss products; synephrine active ingredient (similar to phenylephrine and ephedra); associated with serious cardiac side effects; banned by National Collegiate Athletic Association; increases incidence of elevated blood pressure and heart rate when combined with caffeine (to potentiate weight loss)

Indian ayurvedic herbal preparations: may contain impurities; heavy metal toxicity commonly reported

Ginseng and licorice: instances of overdose common; action of licorice similar to that of aldosterone (increased blood pressure, decreased potassium, and salt and water retention), which inhibits effects of antihypertensive medications; ginseng associated with Stevens-Johnson syndrome and insomnia

Interactions with other drugs: most common issue with herbal preparations; warfarin — number 1 drug for interactions with herbal preparations; interacts with coenzyme Q10 (antioxidant), cranberries (used to treat urinary tract infection), saw palmetto (used to treat benign prostatic hypertrophy), feverfew (used to treat colds), garlic (used to lower cholesterol), green tea (antioxidant), and ginger (antiemetic); St John’s wort — has serotonergic properties (associated with serotonin syndrome when combined with other agents, particularly antidepressants); black cohosh — used to treat menopausal symptoms; associated with liver toxicity; evening primrose oil — anticancer agent; reportedly interacts with seizure medications; saw palmetto — associated with failure of oral contraceptives; goldenseal — used to treat colds; reportedly interacts with antipsychotic agents

Drug interaction checker: available online; patient handouts listing interactions and potential side effects available from National Center for Complementary and Alternative Medicine

Surgery: patients advised to stop all herbal preparations ≥2 wk before surgery

Antihypertensive agents

Ankle swelling: associated with vasodilative effect of dihydropyridine (DHP)-type calcium channel blockers (CCBs; eg, amlodipine, nifedipine); addition of angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) recommended (eg, amlodipine and benazepril [Lotrel]; speaker cautions against combination of ACE inhibitor or ARB and diuretic, which may increase risk for acute renal failure); patients may also switch to non-DHP CCB (either verapamil type [associated with constipation] or diltiazem type [probably best tolerated and associated with less edema and constipation])

Hyperkalemia: associated with spironolactone and ACE inhibitors; spironolactone — hyperkalemia can present within first month of use; monitoring of serum potassium recommended; ACE inhibitors — risk for hyperkalemia increased in patients with underlying renal disease or volume depletion

Hypokalemia: associated with diuretics; incidence and degree of hypokalemia and hyponatremia higher with chlorthalidone than with hydrochlorothiazide (rate of hospitalization with chlorthalidone 3%); vigilance recommended; measure serum potassium 1 to 2 wk after starting chlorthalidone or after increasing dose

Increased levels of serum creatinine (SCr): associated with initiation of ACE inhibitors; not usually worrisome; caused by mechanism of action on arteriole in kidney; initial increase of 10% to 20% expected; reduce dose or discontinue if 50% decline in renal function observed (ie, increase of 0.5 mg/dL if initial SCr <2 mg/dL; increase of 1.0 mg/dL if initial SCr >2 mg/dL); 50% decline in renal function more common if patient has underlying kidney disease, >55 yr of age, or taking nonsteroidal anti-inflammatory drugs (NSAIDs)

Statins: liver function — present recommendation to check liver function tests upon initiation and on as-needed basis; data show that rate of elevated liver transaminase 0.4%; liver toxicity uncommon and dose related; review by Journal of American Geriatric Society found that overall benefit appeared to outweigh risk, even in patients >85 yr of age (based on Cochrane review showing benefit for primary prevention and dose-related benefit for secondary prevention); diabetes — statins associated with increased risk of 0.5%, but risk outweighed by reduction in mortality

NSAIDs and gastrointestinal (GI) toxicity: etodolac (Lodine) least toxic to GI tract; ibuprofen second least toxic to GI tract; ketorolac — highly potent and highly toxic to GI tract, therefore do not use for >7 days per course; effective in patients who cannot take narcotics; naproxen — long acting (12 hr)

Proton pump inhibitors: more effective than misoprostol (Cytotec) at managing GI side effects; nonresponse rate for relieving GI side effects 10%; use lowest effective dose for shortest period of time; take with meals; avoid other medications that may compound GI toxicity

NSAIDs and cardiovascular (CV) toxicity: increased CV risk can occur in first month of use; naproxen has lowest CV risk; etodolac has high risk; evidence-based review found that low-dose aspirin associated with decreased risk for CV disease in patients on long-term therapy with NSAIDs

Weight-loss agents

Phentermine and topiramate (Qsymia): most effective preparation for weight loss and maintenance of weight loss; phentermine sympathomimetic (use with fenfluramine associated with CV toxicity); topiramate antiseizure agent; highly fetotoxic (only available through restricted access; proof of contraceptive use and negative pregnancy test required); associated with some CV toxicity (significant elevation of heart rate); not recommended in overweight patients with CV issues

Orlistat: Xenical (prescription) or Alli (over the counter); technically safest weight-loss agent; taken with meals; prevents absorption of fat; side effects include diarrhea and upset stomach; can result in decreased absorption of fat-soluble vitamins, but not documented in clinical setting; use of multivitamin recommended

Lorcaserin (Belviq): associated with inhibition of serotonin; appetite suppressant; best-tolerated side effects; nausea most common side effect (reason for discontinued use in 30%-40% of cases); risk for serotonin syndrome possible if combined with serotonin-active drugs

Naltrexone and bupropion (Contrave): naltrexone (opioid antagonist) potentiates effect of bupropion (appetite suppressant); weight loss double that of orlistat; not a controlled substance

Liraglutide (Victoza): approved for diabetes and weight loss; associated with thyroid C-cell hyperplasia in mice

Metformin: associated weight loss (5 lb); only antidiabetic agent to specifically decrease morbidity and mortality in overweight patients; top choice for overweight patients <80 yr of age who meet SCr restrictions

Duration of use: each agent has its own guidelines (typically 1-2 yr), but discontinue if ≥5% of body weight not lost in 12 wk

Readings

Bucşa C et al: How many potential drug-drug interactions cause adverse drug reactions in hospitalized patients? Eur J Intern Med, 2013 Jan;24(1):27-33; Davidoff AJ et al: Prevalence of potentially inappropriate medication use in older adults using the 2012 Beers criteria. J Am Geriatr Soc, 2015 Mar;63(3):486-500; Dhamija P et al: Patterns of prescription drug use and incidence of drug-drug interactions in patients reporting to medical emergency. Fundam Clin Pharmacol, 2013 Apr;27(2):231-7; González-Stuart A: Herbal product use by older adults. Maturitas, 2011 Jan;68(1):52-5; Kouladjian L et al: Drug Burden Index in older adults: theoretical and practical issues. Clin Interv Aging, 2014 Sep 9;9:1503-15; Lu WH et al: Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study. CMAJ, 2015 Mar 3;187(4):E130-7; Obreli-Neto PR et al: Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study. Eur J Clin Pharmacol, 2012 Dec;68(12):1667-76; Sabzwari SR et al: Polypharmacy in elderly: a cautious trail to tread. J Pak Med Assoc, 2013 May;63(5):624-7; Schnabel K et al: Use of complementary and alternative medicine by older adults — a cross-sectional survey. BMC Geriatr, 2014 Mar 26;14:38; Tyczynski JE et al: Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study. Drug Saf, 2012 Aug 1;35(8):629-44; Wehling M: Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol, 2014 Oct;70(10):1159-72.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Cheng was recorded at the 38th Annual Eastern Shore Medical Symposium, held June 22-26, 2015, in Rehoboth Beach, DE, and jointly sponsored by Sidney Kimmel Medical College at Thomas Jefferson University and the University of Delaware, with promotional assistance provided by the Medical Society of Delaware. For information about upcoming CME activities from Sidney Kimmel Medical College at Thomas Jefferson University, please visit library.jefferson.edu/jeffcme. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Lecture ID:

IM624101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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