Geriatric Pharmacology. Kwi Bulow, M.D. Clinical Professor of Medicine Director, Academic Geriatric Resource Center

Transcription

1 Geriatric Pharmacology Kwi Bulow, M.D. Clinical Professor of Medicine Director, Academic Geriatric Resource Center

2 Silver Tsunami 2010: 40 million (13%) 2030: 72 million (20%) Baby Boomers ( ) started turning 65 in 2011

3 13% of the U.S. Population Drug Use in Patients > 65 Purchase 33% of all prescription drugs

4 Pharmacotherapy Pharmacokinetics Relationship between drug administration and concentration in the body Absorption Distribution Metabolism Elimination Pharmacodynamics Cellular response to a drug Drug-Receptor interaction Intensity of pharmacological effect

5 Absorption Minimally affected by aging Achlorhydria Tube feeding Concurrent medications Drug-drug and drug-food interactions are more likely to alter absorption Reuben DB et al, 2012 Geriatrics At Your Fingertips, 14th Edition

6 Increase in fat:water ratio Distribution Decrease in plasma protein (albumin) Heart failure and ascites increase body water Fat-soluble drugs have a larger volume of distribution Highly protein bound drugs have a greater active (free) concentration Reuben DB et al, 2012 Geriatrics At Your Fingertips, 14th Edition

7 Metabolism Decrease in liver mass and liver blood flow decrease drug clearance Age related changes in CYP2C19; CYP3A4 and 2D6 are not affected Smoking, genotype, concurrent drug therapy, alcohol and caffeine may have more effect than aging Lower dosage may be therapeutic Reuben DB et al, 2012 Geriatrics At Your Fingertips, 14 th Edition

8 Elimination Age-related decrease in GFR Renal impairment with acute and chronic diseases Decreased muscle mass; serum Cr is not a reliable measure of kidney function

9 Renal Clearance Cockcroft-Gault CrCl = (140-age) x weight 72x serum creatinine Limitations Variability in age-related decline in renal function People with reduced muscle mass Basis for FDA labeled dosing recommendations Not the same as egfr

10 Pharmacodynamic Changes Opioids: prolonged pain relief at lower dosages (e.g. fentanyl and EEG frequency spectra) Benzodiazepines: increased sedation, respiratory depression and postural instability Βeta-blockers: less sensitive to hypotensive effect of betaadrenoreceptor antagonists

11 Beers Criteria 1991: List of potentially inappropriate medications (PIMs) was developed by Beers and colleagues for nursing home residents. 1997, 2003: expanded to include all settings of geriatric care 2000: Medical Expenditure Panel Survey: $7.2 billion related to use of PIMs Adverse drug events are preventable: 27% of events in primary care 42% of events in nursing homes AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

12 Potentially Inappropriate Medications (PIMs) Demonstrated success in improving outcomes by reducing PIMs Centers for Medicare and Medicaid Services (CMS) regulations Medicare Part D Quality measure in National Committee for Quality Assurance (NCQA) Healthcare Effectiveness Data and Information Set (HEDIS) AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

13 Benzodiazepines Highly protein-bound, lipid soluble Widely distributed throughout the body Crosses the Blood Brain Barrier Increase risk of Cognitive impairment Delirium Falls Fractures MVAs AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

14 Short and Intermediate Acting Benzodiazepines Alprazolam (Xanax) Half life 11 hours Lorazepam (Ativan) Half life 9-16 hours Temazepam (Restoril) Half life 8-20 hours Triazolam (Halcion) Half life hours AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

15 Long Acting Benzodiazepines Clonazepam (Klonopin) Half life hours Diazepam (Valium) Half life hours; hours for active metabolite Flurazepam (Dalmane) Half-life hours

16 Zolpidem (Ambien, Intermezzo) Benzodiazepine receptor agonist Adverse effects similar to benzodiazepines Delirium Falls Fractures MVA AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

17 NSAIDs Upper GI ulcers, GI bleed 1% of patients treated for 3-6 months 2-4% of patients treated for 1 year Indomethacin has the most adverse effects AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

18 Dabigatran (Pradaxa) Beers criteria for medications to be used with caution Lack of evidence that benefit outweighs risk in individuals > 80 Greater risk of bleeding than with warfarin in adults > 75 Lack of evidence for efficacy and safety in adults with CrCl < 30 ml/min AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

19 Dry mouth Constipation Orthostatic hypotension Sedation Confusion Urinary retention Anticholinergic Side Effects

20 Drugs with Strong Anticholinergic Properties Antihistamines Diphenhydramine (Benadryl)-Tylenol PM, Advil PM Hydroxyzine (Atarax) Antidepressants Amitriptyline (Elavil) Nortriptyline (Pamelor) Anti-muscarinics Oxybutynin (Ditropan) Tolterodine (Detrol) AGS 2012 Beers Criteria Update Expert Panel, J Am Geriatr Soc 2012

21 Hospitalizations for Adverse Drug Events National Electronic Injury Surveillance System Frequency of hospitalization after ED visits for adverse drug events in older adults 100,000 admissions per year 2/3 of admissions involved 4 medications/class Warfarin (33%) Insulin (14%) Anti-platelet agents (13%) Oral hypoglycemic agents (11%) Budnitz DS et al, N Engl J Med 365;21

22 CHADS Score-Stroke Risk per 100 Person Years Points On Warfarin No Warfarin Gage BF et al, JAMA 2001 Jun 13;285(22)

23 Hospitalizations for Adverse Drug Events II 1.2% -HEDIS high-risk medications 6.6% -Beers-criteria medications More than half involved Digoxin

24 Narrow therapeutic index Toxicity seen at <2 ng/ml Renal clearance Drug-drug interactions Measuring levels < mg daily Digoxin

25 40% take 5-9 medications 18% take 10 or more Less Is More Survey/AnnualRpt/SloneSurveyWebReport2006.pdf

26 Mrs. Poly (3 MDs) Acyclovir 800 mg 2x daily Amitriptyline 10 mg nightly Bupropion XL 150 mg daily Phenytoin 100 mg 3x daily Levetiracetam (Keppra) 500 mg 2x daily Gabapentin 300 mg 3x daily Topiramate 50 mg 2x daily Folic acid 400 mcg 2x daily Fentanyl patch 25 mcg q48 h Lutein 40 mg daily Amlodipine 5 mg daily Pantaprazole 40 mg daily Vitamin C 1000 mg daily Hydromorphone 2 mg q4hrs PRN Docusate 100 mg daily as needed Diphenoxylate-atropine (Lomotil) 2 tablets q6h PRN Acetaminophen 650 mg q6h PRN Aspirin 81 mg daily

27 Avoid Polypharmacy What are you treating? What are your therapeutic end points? Is pharmacological treatment the best option? Is there proven efficacy? Review for interactions with current medications Review for duplication: same class or actions Avoid starting a medication to treat the side effects caused by another one Are there medications that you can stop? Communicate with other prescribers Re-evaluate!

28 N=1 Each patient is unique Increase in variability Assess carefully Apply data judiciously Re-evaluate constantly

29 What are they taking? Current prescriptions Old prescriptions Prescriptions from specialists Spouse s prescriptions Over the counter medications Compound pharmacy Vitamins, supplements Naturopathic medications Medications purchased locally Mail order medications

30 Alcohol = Drug Drug-alcohol interactions 3-9%: 12-2 drinks/week 2-4%: alcoholism

31 Prescribing for the Older Patient Include the medication s purpose Include generic and brand names Educate the patient/caregiver Start low; go slow Keep it simple Encourage the use of a pillbox Discuss cost/affordability

32 Medicare Part D Coverage Gap -pay 100% of drug costs after $2250 -pay 5% of drug costs after $5100 -decreased prescriptions for -blood pressure -lipid -pain -depression -acid suppression Li P et al, Ann Intern Med 2012;156

33 Thank you!