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Principles of Geriatric Drug Therapy Beata Ineck, Pharm.D, BCPS, CDE University of Nebraska Medical Center College of Pharmacy Omaha VA Objectives 1. Review predictors for adverse drug events in the elderly. 2. Discuss pharmacokinetic changes in the elderly and how they alter medications. 3. Discuss pharmacodynamics and the effects of aging. 4. Review criteria for appropriate prescribing in the elderly. • 30% of admissions due to drug related problems • 2/3 of nursing facility residents have ADE over 4 years • 106,000 deaths and $85 billion for medication related problems in 2000 • 5th cause of death Arch Intern Med 2003;163:2716-2724 Predictors of Adverse Drug Events • • • • • • • > 4 prescription medications Length of stay in hospital > 14 days > 4 active medical problems Admission to general medical unit History of alcohol use Lower mean MMSE score 2-4 new medications added during hospitalization Clin Geriatr Med 1998;14:681. J Gerontol 1998;53A9A):M59 JAMA 2003;289:1107 AGE RELATED CHANGES Geriatric Brain Function • Brain mass and cerebral blood flow • BBB may become more permeable • Secondary memory may be diminished • Short term memory difficulties 2° to decline in – Learning – Information retrieval – Processing speed Pharmacokinetics and Aging • Behavior of drugs in the body • Absorption, distribution, metabolism, elimination • Removal of drugs from the body is slowed Absorption • Increased GI pH – Calcium carbonate, “azoles”, iron • Slower gastric motility/emptying • Increased fat/decreased muscle – Transdermal, IM, SQ • Dysphagia may potentially alter absorption Overall, extent or rate of absorption not significantly altered Distribution • Increased Vd for water soluble drugs • in body fat • in serum proteins Pharmacokinetics and Aging • Identify the drug below that is metabolized more slowly in elderly adults than in young adults. Amlodopine Atorvastatin Metoclopramide Morphine Pharmacokinetics and Aging • Identify the drug below that is metabolized more slowly in elderly adults than in young adults. Amlodopine Atorvastatin Metoclopramide Morphine Metabolism • Drugs with a high extraction ratio (ER) • Decreased clearance: • reduced hepatic blood flow • reduced liver mass High Extraction • Examples of high ER drugs with decreased clearance: – Meperidine, morphine – Metoprolol, propranolol – Amitriptyline, nortriptyline – Verapamil Metabolism • Decreased oxidative (phase I, P-450) metabolism due to reduced liver volume and perfusion. – Diazepam, piroxicam, theophylline, quinidine – Confounded by smoking, diet, drug interactions, race, sex, and frailty Patient Case An 82 year old white woman has been having anxiety due to the anniversary of her husband’s death. Which one of the following would be the safest pharmacologic treatment for her anxiety? • • • • Alprazolam Chlordiazepoxide Diazepam Lorazepam An 82 year old white woman has been having anxiety due to the anniversary of her husband’s death. Which one of the following would be the safest pharmacologic treatment for her anxiety? • • • • Alprazolam Chlordiazepoxide Diazepam Lorazepam Metabolism • No change in phase 2 metabolism – Lorazepam, oxazepam, temazepam Renal Elimination • Identify the drug below that is renally excreted more slowly in elderly adults than in young adults. Celecoxib Gabapentin Morphine Sertraline Renal Elimination • Identify the drug below that is renally excreted more slowly in elderly adults than in young adults. Celecoxib Gabapentin Morphine Sertraline Renal Elimination Decrease in: • • • • • Kidney mass Nephron size and number Renal blood flow Tubular secretion Glomerular filtration rate Examples of Renally Eliminated Drugs – Metoclopramide, H2-blockers, digoxin, gabapentin, atenolol, nadolol, allopurinol, magnesium laxatives, chlorpropamide – Aminoglycosides, cephalosporins, penicillins, quinolones, vancomycin Renally-Eliminated Active Metabolites • Meperidine (normeperidine) • Morphine (M3G and M6G) • Propoxyphene (norpropoxyphene) • Venlafaxine (O-desmethylvenlafaxine) • Carbamazepine (Carbamazepine-10,11epoxide) Drug Dosing and Measures of Renal Function • Use creatinine clearance – Calculated or measured Estimated CrCl (ml/min) = (140-age) x (IBW) * 0.85 for females 72 x SCr – If SCr < 1, use SCr = 1 to adjust for muscle mass • Serum creatinine (used alone) – An unreliable marker in elderly Example: Creatinine Clearance vs. Age in a 5’5”, 55 kg Woman Age Scr CrCl 30 1.1 65 50 1.1 53 70 1.1 41 90 1.1 30 Pharmacodynamics and Aging • Some effects are increased – alcohol increases drowsiness and lateral sway – e.g. diazepam, morphine, theophylline • Some effects are decreased – diminished HR response to -blockers Pharmacodynamics: Acetylcholine Blockers • Decreased tolerance to adverse effects • Constipation, urinary retention • Dry mouth, dry eyes, dry skin • Memory impairment • Delirium Pharmacodynamics: Digoxin • Pattern of toxicity – young vs. elderly • Increased cardiac sensitivity to digoxin due to: – Hypokalemia, hypothyroidism, hypomagnesemia, hypercalcemia, acute hypoxia Pharmacodynamics: Dopamine Blockers • CNS dopamine decline • Adverse drug effects from antipsychotic agents, metoclopramide – Extrapyramidal effects – Parkinsonism – Tardive dyskinesia Risk Factors for Drug Related Problems in the Elderly • Suboptimal prescribing • Medication Errors • Medication nonadherence Medication Appropriateness Index 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Is there an indication? Is the medication effective for the condition? Is the dosage correct? Are the directions correct? Are the directions practical? Are there clinically significant drug-drug interactions? Are there clinically significant drug-disease interactions? Is there unnecessary duplication? Is the duration of therapy acceptable? Is this drug the least expensive alternative? Additional Criteria for Drug Use • Compatible safety and side effect profile • Low risk of drug/nutrient interactions • T1/2 < 24h with no active metabolites • No adjustments for renal/hepatic function • Strength/dosage form match recommendations for older adults Newer Drugs • What is unique about the new drug? • Is clinical data available? • How does it compare with traditional therapy? • Cost? • Coverage by third party payers? • Does potential advantage justify risk of new drug? How to Prescribe Appropriately 1. Obtain complete drug history 2. Avoid prescribing prior to diagnosis 3. Review medications regularly 4. Know actions, adverse effects, toxicity 5. Start at low dose and titrate 6. Try not to start two drugs at the same time 7. Reach therapeutic dose before switching/adding 8. Consider non-pharmacological alternatives How to Prescribe Appropriately 7. Educate patient/caregiver 8. Use one drug to treat two conditions 9. Keep regimen as simple as possible 10. Caution with combination products 11. Communicate with other prescribers 12. Avoid drugs from same class/similar actions 13. Avoid one drug to treat side effect of another Drug 1 Adverse drug effect misinterpreted as new medical condition Drug 2 Adverse Drug Effect Prescribing Cascade BMJ. 1997;315:1097 Underprescribing Overprescribing Optimize Drug Therapy Patient Case A 78 year old African American man has a hx of falls. He also has a hx of DM, HTN, depression and insomnia. He is currently taking glipizide 5mg qd, HCTZ 25mg qd, sertraline 25mg qd, and diazepam 2mg prn insomnia. His BP is 126/62, HR 68, RR 18, CBC WNL, BUN/SCr 28/1.2, HbA1c 7.2%, Chol 109, TG 58, HDL 41, LDL 56. Which one of the following medications is underutilized? a. b. c. d. Aspirin Beta blocker HMG CoA reductase inhibitor Warfarin a. b. c. d. Aspirin Beta blocker HMG CoA reductase inhibitor Warfarin Undertreatment • CAD – -blockers – Aspirin • Anticoagulation for A Fib • HTN • Pain Drug-Food Interactions • • • • Warfarin and vitamin K Methotrexate and folate Phenytoin and vitamin D metabolism Impact on appetite – taste alteration – decreased saliva production Drug-Disease Interactions • Decongestants and anticholinergics BPH • CCB’s and anticholinergics constipation • NSAIDs Heart Failure NSAIDs • Side effects – GI hemorrhage – Decline in GFR • Decreased effectiveness of diuretics and antihypertensives • For mild OA, use acetaminophen Anticipate Side Effects • Narcotics – begin stimulant laxative – docusate not sufficient • Steroids – osteoporosis prevention – hyperglycemia Drug-Induced Osteoporosis • Identify the drug listed below that has been associated with osteoporosis in elderly adults. a.Alprazolam b.Divalproex c.Fluoxetine d.Risperidone Drug-Induced Osteoporosis • Identify the drug listed below that has been associated with osteoporosis in elderly adults. a.Alprazolam b.Divalproex c.Fluoxetine d.Risperidone Drug-Induced Osteoporosis • Glucocorticoids • Anticonvulsants • Excessive thyroid replacement • Gonadotropin-releasing hormone analogues • • • • • • Potential Barriers to Improving Adherence Poor attitude Memory deficits Language Literacy Cultural beliefs Alternative health beliefs • Poor support • Pride • Denial • Fear or embarrassment • Side effects • Religious beliefs • Unable to “see” results of drug therapy • Lack of choices • Cost Vermiere E, et al. J Clin Pharm Ther. 2001;26:331-342. Factors Influencing Ability to Comply • 3 chronic conditions • > 5 prescription medications • 12 medication dosages per day • Regimen changed 4 times in past 12 months • 3 prescribers • Significant cognitive or physical impairment • Living alone in community • Recently discharged from hospital • Reliance on caregiver • Low literacy Medication cost • Demonstrated poor compliance history Med Care 1991;29:989 Brown Bag • • • • Rx, OTC, Herbal, Vitamins, Supplements Ask what each medication for Ask how it is taken Discontinue unnecessary medications Patterns of Herbal Therapy Use Among Men and Women 65+ Year Old • Men – – – – – – – Garlic Glucosamine Saw palmetto Ginkgo biloba Lecithin Chondroitin Ginseng • Women – – – – – – – Ginkgo biloba Glucosamine Garlic Ginseng Chondroitin St. John’s wort Echinacea Kaufman DW et al, JAMA 2002. OTC’s • Elderly take average of 2-4 OTC’s qd • Laxatives used in 1/3 to 1/2 • NSAIDs, antihistamines, H2 blockers ALL CAN CAUSE SIDE EFFECTS! Strategies to Ensure Adherence • Find out about patient/family expectations; explain why some may not be met • Provide information on illness / consequences of nonadherence • Use a behavioral contract • Increase motivation by enlisting patient/family in decision-making process Haynes RB, et al. Patient Education and Counseling. 1987;10:155-166 Use Adherence Enhancing Aids • • • • • Medication record Drug calendar Medication boxes Magnification for insulin syringes Spacers for MDI’s Strategies to Ensure Adherence • Ask patient/family to repeat instructions • Keep directions / labels simple,use lay terms • Give clear instructions on drug regimen, preferably in writing • Emphasize importance of adherence at each visit • Involve patient’s spouse or partner Haynes RB, et al. Patient Education and Counseling. 1987;10:155-166 • Questions?