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2015: Polypharmacy and Aging-Kejriwal


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Polypharmacy and Aging

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2015: Polypharmacy and Aging-Kejriwal

  1. 1. Kamal Kejriwal M.D., CMD, AGSF, FAAFP Program Director Geriatric Medicine Fellowship SCPMG Fontana Polypharmacy and Aging
  2. 2. Larry Zelman, Pharm.D, CGP Clinical Pharmacist VAMC San Diego
  3. 3. 3 Disclosure No relevant financial relationships with commercial interests
  4. 4. 4 The central question in all of modern American medicine… Well, what pills should I give her for that?
  5. 5. 0w1FE 5
  6. 6. 6 Topics Covered • Challenges of geriatric pharmacology • Aging and pharmacokinetics • Aging and pharmacodynamics • Psychotropic use in Nursing Facilities
  7. 7. 7 “It’s just because I’m OLD” FALSE You must understand the underlying pathophysiology of diseases, normal pharmacodynamics and pharmacokinetic changes with aging, and drug-drug and drug-disease interactions!!
  8. 8. 8 Why Geriatric Pharmacotherapy is Important Persons aged 65 and older are prescribed the highest proportion of medications in relation to their percentage of the U.S. population • Now, 13% of total population buy 33% of all prescription drugs. • In Elderly populations there are more deaths due to ADE than MVA, Breast cancer or AIDS. • By 2040, 25% of total population will buy 50% of all prescription drugs.
  9. 9. 9 WHY GERIATRIC PHARMACOTHERAPY IS IMPORTANT 0 10 20 30 40 50 60 70 80 90 100 Present 2040 People 65+ 65+ share of prescriptions People <65 <65 share of presciptions Now, people age 65+ are 13% of US population, buy 33% of prescription drugs By 2040, will be 25% of population, will buy 50% of prescription drugs
  10. 10. 10 Why Geriatric Pharmacotherapy is Challenging? • FDA- approved and off-label indications expansion • Managed-care formularies change frequently • Knowledge of drug-drug interactions advances • Drugs change from prescription to OTC • “Nutriceuticals” (herbal preparations, nutritional supplements) are booming
  11. 11. 11
  12. 12. 12 Pharmacokinetics • Absorption • Distribution • Metabolism • Elimination
  13. 13. Case Study An 80yo woman is taking calcium carbonate 500mg qday for osteoporosis. She is also on alendronate 70mg qweek, atenolol 50mg qday, and omeprazole 20mg qday x 2years. Which of the following pharmacokinetic properties associated with aging can change the expected outcome of treatment? A. Absorption B. Distribution C. Metabolism D. Excretion
  14. 14. 14 Aging and Absorption • Amount absorbed (bioavailability) is not changed • Peak serum concentration may be lower and delayed • Exceptions: drugs with extensive first-pass effect (bioavailability may increase because less drug is extracted by the liver, which is smaller with reduced blood flow)
  15. 15. 15 Drug Interactions: Absorption • Cations may chelate antibiotics (quinolones, tetracyline) • Binding resins, psyllium, sucralfate • Antacids may prevent absorption (ketoconazole)
  16. 16. 16 Factors that Affect Absorption (1 of 2) • Route of administration • What is taken with the drug? • Co-morbid illnesses
  17. 17. 17 Factors that Affect Absorption (2 of 2) • Divalent cations (calcium, magnesium, iron) can affect absorption of many fluoroquinolones (e.g., ciprofloxacin) • Enteral feedings interfere with absorption of some drugs (e.g., phenytoin) • Increased gastric pH may increase or decrease absorption of some drugs • Drugs that affect GI motility can affect absorption
  18. 18. 18 Effects of Aging on Volume of Distribution (Vd) •  body water  lower VD for hydrophilic drugs •  lean body mass  lower VD for drugs that bind to muscle •  fat stores  higher VD for lipophilic drugs •  plasma protein (albumin)  higher percentage of drug that is unbound (active)
  19. 19. Case Study A 75yo male has a 20 year history of a seizure disorder. He has been seizure free for the past 4 years. He is on phenytoin 200mg qday. Labs are drawn in your clinic today and the phenytoin level is 6.5mg/L (therapeutic range 10-20mg/L) and his albumin is 2.3gm/dl. The phenytoin dose needs to be: A. Increased to 300mg qday B. Increased to 400mg qday C. Decreased to 100mg qday D. Maintained at 200mg qday
  20. 20. 20 Changes in Distribution: Protein Binding • Reduced protein binding with age • Reduced protein concentrations with disease • Affects serum levels of drugs that bind to proteins • Examples: fentanyl, theophylline, sulfonylureas, warfarin and digoxin
  21. 21. 21 Aging and Metabolism Metabolic clearance of a drug by the liver may be reduced because: • Aging decreases liver blood flow, size, and mass, and • The liver is the most common site of drug metabolism
  22. 22. Case Study A 79yo male has history of gout, maintained on colchicine 0.6mg qday and allopurinol 300mg qday. Pt has developed a gastric ulcer and clinician starts H.Pylori regimen of amoxicillin, clarithromycin and omeprazole. Which pharmacokinetic property can change the expected outcome to treatment? A. Absorption B. Distribution C. Metabolism D. Excretion
  23. 23. 23 Cytochrome P-450 • Major pathway for drug metabolism • Several isoenzymes, genetic susceptibility • Drug-drug interactions: • Enzyme inhibition: competition with another drug for the enzyme binding site: INCREASE DRUG LEVELS • Enzyme induction: a drug stimulates the synthesis of more enzyme protein, enhancing the enzyme’s metabolizing capacity: DECREASE DRUG LEVELS
  24. 24. 24 Why the Metabolic Pathways Matters • Phase I pathways (e.g., hydroxylation, oxidation, dealkylation and reduction) convert drugs to metabolites with <, =, or > effect than parent compound • Phase II pathways convert drugs to inactive metabolites that do not accumulate With few exceptions, drugs metabolized by Phase II pathways are preferred for older patients.
  25. 25. 25 Changes in Metabolism • Reduced hepatic mass • Reduced hepatic circulation • Decreased phase I metabolism-oxidative or reduction reactions via cytochrome P450 • Examples: diazepam, barbiturates, lidocaine • No change in phase II metabolism-conjugative reaction with glucuronyl transferase • Examples: lorazepam, oxazepam
  26. 26. 26 CYTOCHROME P-450 CYP3A4 Metabolizes: Fentanyl, methadone, Acetaminophen Erythro, Clarithromycin Itra- and ketoconazole, Amiodarone, lidocaine, quinidine, Calcium channel blockers Sertraline, nefazadone Alprazolam, zolpidem, triazolam Astemizole, loratadine, terfenadine Cyclosporine Sex hormones, cortisol Carbamazepine Induced by: Barbiturates Carbamazepine Glucocorticoids Phenytoin Inhibited by: Cimetidine Erythro, clarithromycin Diltiazem, nicardipine, verapamil Itra-, ketoconozole Fluoxetine, methylphenidate
  27. 27. 27 Drug Interactions: Metabolism • Codeine is prodrug—requires 2D6 for activation • Fluoxetine inhibits 2D6 • Genetic variability
  28. 28. 28 Other Factors that Affect Metabolism • Gender (e.g.,oxazepam is metabolized faster in older men than older women) • Hepatic congestion from heart failure (e.g., reduces metabolism of warfarin) • Smoking (e.g., increases clearance of theophylline)
  29. 29. oZl8 29
  30. 30. How to Avoid Getting Into Trouble with Drugs in the Elderly
  31. 31. 31
  32. 32. 32 ADEs Prescribing Cascade Source Note: Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315(7115):1097. Reprinted with permission. DRUG 1 DRUG 2 Adverse drug effect- misinterpreted as a new medical condition- Adverse drug effect- misinterpreted as a new medical condition
  33. 33. 33 How to Avoid Getting Into Trouble with Drugs in the Elderly • Use proper prescribing etiquette • Watch for drug-drug, drug-disease, and drug-food interactions • Don’t prescribe bad medications
  34. 34. 34 Appropriate Drug Prescribing (proper etiquette) • Review current prescription and non- prescription medications, medical history, labs • Ask about drug allergies, adverse reactions, use of alcohol • Start low and go slow but treat adequately • Maximize dose before switching to another drug • Avoid starting two drugs at the same time
  35. 35. 35 Watch for Drug-Drug, Drug-Disease, and Drug-Food Interactions
  36. 36. 36 Key Concepts in Elimination • Half-life: time for serum concentration of drug to decline by 50% • Clearance: volume of serum from which the drug is removed per unit of time (usually expressed in hours)
  37. 37. Case Study 83yo female with CAD, HTN, type 2 diabetes, depression, GERD and chronic low back pain. She weighs 72kg , height 5’3” and her SCr is 2.0mg/dl. Her med list includes metoprolol 50mg bid, gabapentin 900mg tid, glipizide ER 5mg qday, citalopram 20mg qday, acetaminophen 500mg tid and ranitidine 300mg qhs. Which of the following medication dosages should be reduced? A. Metoprolol B. Gabapentin C. Citalopram D. Ranitidine E. B and D
  38. 38. 38 Kidney Function is Critical for Elimination • Most drugs exit body via kidney • Reduced elimination  drug accumulation and toxicity • Aging and common geriatric disorders can impair kidney function
  39. 39. 39 Effects of Aging on the Kidney •  kidney size •  renal blood flow •  number of functioning nephrons •  renal tubular secretion Result: Lower glomerular filtration rate
  40. 40. 40 Serum Creatinine Does NOT Reflect Creatinine Clearance •  lean body mass  lower creatinine production and •  glomerular filtration rate (GFR) Result: In older persons, serum creatinine stays in normal range, masking change in creatinine clearance (CrCl)
  41. 41. 41 Changes in Elimination • Decline in glomerular filtration and tubular excretion • Estimation of Creatinine Clearance: • COCKROFT AND GAULT EQUATION Cr Cl = [140- Age (y)] X Weight (kg) 72 X Cr (Multiply total by .85 if pt is female) • Examples: aminoglycosides, allopurinol, digoxin, lithium, atenolol
  42. 42. 42 Pharmacodynamics Definition • Time course and intensity of pharmacologic effect of a drug The Impact of Aging • May change with aging, e.g.: • Benzodiazepines may cause more sedation and poorer psychomotor performance in older adults. Likely cause: reduced clearance of the drug and resultant higher plasma levels • Older patients may experience higher levels of morphine with longer pain relief
  43. 43. 43 Age-Related Pharmacodynamics • Autonomic nervous system • Central nervous system • Gastrointestinal system
  44. 44. 44 Age-Related Pharmacodynamics: Autonomic nervous system • Decreased baroreceptor response • Increased blood pressure sensitivity to vasodilatory agents
  45. 45. 45 Age-Related Pharmacodynamics: Central nervous system Increased effect at equal concentration • Benzodiazepines • Narcotics
  46. 46. 46 Drug Interactions: Elimination • Increased half life • Increased serum concentration • Problem for drugs with narrow therapeutic index
  47. 47. 47 Drug-Disease Interactions • Urinary retention: anticholinergics, tricyclics, alpha-agonists • Constipation: anticholinergics, narcotics, calcium channel blockers, tricyclics • Falls: benzodiazepine • Postural hypotension: tricyclics, diuretics, antihypertensives.
  48. 48. 48 Drug-Disease Interactions (cont) • Delirium: benzos, narcotics, anticholinergics • Exacerbation of CHF: NSAIDs • Worsening of urinary incontinence: diuretics, alpha blockers
  49. 49. Beers list of PIMS 2015 Update Guideline for nitrofurantoin is relaxed for Creatinine Cl from 60 to 30 Opioids been added to list of CNS drugs to avoid in pt with h/o falls and fractures. Anticoagulants dose should be adjusted based on Cr Cl. Avoid PPI for greater than 8 weeks Nasal Saline to use as alternative to antihistamines 49
  50. 50. CHOOSING WISELY 50
  51. 51. Don’t prescribe a medication without conducting a drug regimen review. #1 Older patients disproportionately use more prescription and non-prescription drugs than other populations, increasing the risk for side effects and inappropriate prescribing. #2Polypharmacy may lead to diminished adherence, adverse drug reactions and increased risk of cognitive impairment, falls and functional decline #3 Annual review of medications is an indicator for quality prescribing in vulnerable elderly. 51
  52. 52. Don’t use benzodiazepines or other sedative- hypnotics in older adults as first choice for insomnia, agitation or delirium. #1Large scale studies consistently show that the risk of motor vehicle accidents, falls and hip fractures leading to hospitalization and death can more than double in older adults taking benzodiazepines and other sedative- hypnotics. #2 Older patients, their caregivers and their providers should recognize these potential harms when considering treatment strategies for insomnia, agitation or delirium. #3 Use of benzodiazepines should be reserved for alcohol withdrawal symptoms/delirium tremens or severe generalized anxiety disorder unresponsive to other therapies 52
  53. 53. Psychotropic Use in Long Term Care Facilities Please do not use the above medications as your First Line Non Pharmacological Approaches first Title 22 requires the consent to be taken by the provider prior to administration of these meds. 53
  54. 54. c 2007 ASCP 54 F329 - Unnecessary Meds Regulations • Antipsychotics - Based on a comprehensive assessment of a resident, the facility must ensure that: – Residents who have not used antipsychotic drugs are not given these drugs unless antipsychotic drug therapy is necessary to treat a specific condition as diagnosed and documented in the clinical record; and – Residents who use antipsychotic drugs receive gradual dose reductions, and behavioral interventions, unless clinically contraindicated, in an effort to discontinue these drugs
  55. 55. CASE STUDY 85yo woman admitted to a nursing facility for short term rehab after a fall and wrist fracture. PMH includes Type 2 Diabetes, HTN, recent DVT, neuropathic pain, hyperlipidemia. Current meds include: Metformin 1000mg bid, Hydrochlorothiazide 25mg qday, Simvastatin 40mg qpm, Gabapentin 800mg tid, Pantoprazole 40mg qday. Recently started meds include Warfarin 5mg qpm, Diltiazem SA 240mg qday, Zolpidem 10mg qhs, Oxycodone 10mg q4h prn pain, Risperidone 2mg bid. 3 days later, patient was c/o lethargy, excessive sedation, constipation, muscle weakness/pain, N/V and pt seemed confused according to nursing staff.
  56. 56. CASE STUDY (cont) Labs were drawn and some were as following: BUN 55, SCr 1.9 (baseline 0.9-1.1), Na 128, K 3.1, Albumin 2.2 INR 3.8 ALT 65 AST 74 BP 98/65, HR 65 Wt 65kg Ht 64in
  57. 57. CASE STUDY (cont) Thoughts/recommendations??
  58. 58. 58 Does this sound Familiar? Decreased use of Inappropriate meds in Elderly ( 65 yrs. and older) improves hospital safety, reduces length of stay and rate of readmissions. Examples of potentially inappropriate meds to avoid in Elderly: -Diphenhyramine, Promethazine, Hydroxyzine, amitriptyline, imipramine, methocarbamol, trimethobenzamide, meperidine and diazepam.
  59. 59. Innovative pill box reminders Medminder® : $40-65 per month. Looks like traditional pill boxes, 7 day (qid) boxes that lock. Flashing light/audible/text message/phone calls for reminders. Also, caregivers can get reports via text/emails/internet Locked medication systems (eg e-pill): $200- 500. Dispensers that lock/alarm, like a small omnicell/pyxis machine. iPhone apps: Free-$3.99. Virtual pillbox. Can set medications, dosages and times a dose is needed. Alarms, reminders, etc.
  60. 60. Thank you!