Prescribing in the elderly

1. Carolyn Glover Registered Pharmacist February 28, 2013 Prescribing in the elderly

2. Objectives • Understand pharmacodynamics and pharmacokinetics of the elderly • Identify high risk patients and high risk drugs • Discuss relevance of drug interactions and polypharmacy

3. Age related Physiologic changes • Endocrine • CNS • Cardiovascular • Skeletal • Genitourinary • Immune system • Pulmonary • Liver • Oral • Sensory • Renal • GI • Body composition

4. Age related changes • Increasing comorbidities • Polypharmacy • Aging results in physiologic changes of • absorption • distribution • metabolism • elimination of drugs

5. Absorption • Gastric PH increases with age • Decreased absorptive surfaces and decreased visceral blood flow • Decreased gastric emptying • Leads to • increased contact time with stomach-GI bleeds with NSAIDS • Increased PH reduces absorption of medications needing acidic environment (ie calcium, ketoconazole, iron)

6. Distribution • Increase in adipose tissue leads to increase in fat soluble medications (benzodiazepines, propanolol, barbituates) • Decrease in body water, leading to lower volume for water soluble medication (increased levels of lithium, gentamicin, ethanol) • Possible reduction is albumin can increase drugs like phenytoin, digoxin, warfarin, theophylline

7. Metabolism-Hepatic Changes • Decrease in hepatic flow as well as decrease in liver size leads to decrease clearance and increased half life for oxidative metabolism drugs • Medications affected- propanolol, diazepam, morphine • Elderly take more drugs which are competing for the same P450 enzymes to metabolize leading to drug interactions

8. Elimination • Decreased renal blood flow and decreased renal mass • GFR and tubular secretory function decreases with age • Creatinine production deceases with decreased muscle mass making CrCl more unpredictable • HCTZ, atenolol, digoxin, lithium etc. • Titrate to effect rather than empirically dosing • Look for trending eGFR to make decisions instead of based on a single Scr result

9. Pharmacodynamics(Target Organ Sensitivity to Drug) • Can have change in receptor binding, decrease in # of receptors or altered action of receptors • Decrease in receptor response will decrease effect of adrenergic meds (leading to less bradycardia with beta blockers) • Increase in receptor response increases effect and toxicity of morphine • Increase receptor response to anti-cholinergics increases confusion, constipation and urinary retention effects

10. Who are High risk Patients? • Patients with multiple prescribers and/or multiple co-morbidities • Over 85 years (30% of >85yrs had claims for >10drug classes) • More than 6 daily medications • Low BMI ( < 22) • Cognitive impairment • Decreased renal function

11. Compliance Issues= High Risk Patients • Pill burden is the total # pills/day leads to non-compliance or poor compliance • Non compliance can lead to significant withdrawal events-ie tachycardia with Beta blockers; rebound hyperacidity with PPI; rebound insomnia with benzos

12. Non Compliance leads to Hospitalization • 20% of prescriptions written for seniors are not filled • 80% compliance problems due to perception that drug is unnecessary or that it will lead to ADR • Also could be forgetfulness, difficulty hearing or seeing instructions, inability to understand the purpose of the medication, trouble opening vials

13. What are dangerous Drugs? • Survey found 20% of hospital admissions were due to drug related events • 40% of delirium is drug induced • Classes of dangerous medications implicated include psychotropics, NSAIDS, hypoglycemics, diuretics, digoxin, warfarin and anticholinergics (see anticholinergic list in Rxfiles under “dementia”)

14. How to use High Risk Drugs • Caution with these classes of medications • Does the patient even need the drug? • Is this the best drug in its class for the elderly? • Can you modify the titration to avoid ADRs? • Medications that contribute to hospitalization=warfarin + Insulin + oral antiplatelets + oral Hypoglycemics = 70% of the drug related ER visits

15. Misuse of Drugs • Best practise guidelines are encouraging medication regimes that are more complex, leading to polypharmacy • Elderly patients have multiple chronic conditions which lead to multiple prescribers, increasing ADRS • Overuse of a particular medication in an effort to improve symptoms resulting in sometime exponential side effects (ie. benzos for sleep) • Underuse of medications from patient (ie. pain medication prescribed as PRN) or from prescriber (warfarin due to hemorrhagic concerns)

16. Misuse of Drugs Continued.. • Most Canadians >80yrs have 2 or more conditions that require preventative medications like statins, aspirin, beta blockers, ACE inhibitors, anti-hypertensives, bisphosphonates, vitamin D • Patients take medications (prescribed or OTC) in response to symptoms the patient has, often it is an ADR to the preventative medications

17. Common Prescribing Cascades • Ibuprofen hypertension antihypertensive edema diuretic potassium • Gabapentin edema diuretic potassium • Lithium tremor propranolol depression SSRI • Amitriptyline cognition donepezil • Narcotic constipation sennosidesdiarrhea

18. Drug Interactions • Drug interactions can require an adjustment in 1 medication, discontinuation of 1 medication or monitoring but continuing with both meds • European study found most common DI adjustments were: • Warfarin + ABX(risk of bleed) • Warfarin + phenytoin (risk of bleed and phenytoin toxicity) • ACE/ARBS +/- spironolactone +/-potassium supplements (hyperkalemia) • Digoxin + amiodarone/verapamil causing digoxin toxicity

19. Significant Drug Interaction Hospital Admissions • Digoxin + furosemide • ACE/ARB + potassium supplements • Acetaminophen + warfarin • Increase in Adverse events associated when more than 6 meds • DON’T forget to ask about the OTCs that elderly are often taking

20. Polypharmacy • More than 6 medications • Any symptom in an elderly patient should be first considered a drug side effect until proven otherwise. This avoids prescribing further medications

21. Conditions That Could Result from Polypharmacy • QT prolongation • Serotonin syndrome • Delirium/dementia • Xerostomia • Falls and unsteadiness

22. Lack of Evidence • Limited info in literatures/studies on drugs used for patients >80yrs since meds are not generally tested in this population • 3/155 RCTs are exclusively with the elderly • Exclusion criteria leads to studying only healthy, older subjects which is NOT the real world patients we deal with every day

23. Coroner’s report 83yr old death • In 2006, AS fell, fractured wrist, ribs and pelvic fracture needing escalating doses of oxycodone • Was on high dose oxycodone from fall 2006.Admitted to retirement home in 2007-developed abdominal distention, nausea, diarrhea. Txt= loperamide, dimenhydrinate. • Transferred to hospital and found to have heart failure TXT=furosemide, dimenhydrinate, morphine, scopolamine, fleet enema • Died 15hrs after hospital arrival-toxicologic reported supratherapeutic levels of oxycodone, diphenhydramine, morphine, lorazepam acetaminophen and chlorpheniramine • NOTE: heart failure impairs metabolism increasing ADR • NOTE: Constipation may present as diarrhea –loperamide should not be given when pt on opioids • NOTE: number of OTC drugs listed

24. Strategies • Use screening tools • Beers criteria • STOPP/START criteria • Identify prescribing cascades • Engage in “deprescribing” • Appropriateness- Indicated, Compliance, Effective, Safe (ICES) • Calculate and reduce pill burden • Adjust guidelines for frail elderly

25. Find the Balance