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Geriatric Polypharmacy, The Good The Bad And The Ugly

Geriatric Polypharmacy, The Good The Bad And The Ugly. John Kashani DO Staff Toxicologist, New Jersey Poison Center Attending, St. Joseph’s Regional Medical Center. Objectives. Discuss the epidemiology of the aging population Discuss polypharmacy and adverse drug reactions

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Geriatric Polypharmacy, The Good The Bad And The Ugly

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  1. Geriatric Polypharmacy, The Good The Bad And The Ugly John Kashani DO Staff Toxicologist, New Jersey Poison Center Attending, St. Joseph’s Regional Medical Center

  2. Objectives • Discuss the epidemiology of the aging population • Discuss polypharmacy and adverse drug reactions • Outline pharmacokinetics as it relates to the aging population

  3. Objectives • Outline potentially inappropriate medications for the elderly population • Discuss clinically significant drug interactions • Provide a rational approach to elderly medication prescribing • Illustrate polypharmacy cases

  4. Introduction • Over 30 new medications are introduced each year • Recognizing drug interactions is a daily challenge and is becoming increasingly more difficult • Multiple drug regimes carry the risk of adverse interactions

  5. Introduction • Precipitant drugs modify the object drugs absorption, distribution, metabolism, excretion or clinical effect • Additionally, newly introduced medications, and medications with new indications may have multiple pharmacologic effects

  6. Introduction • The population is steadily aging: • Greater than 65 years old • 12% of the United States Population • 43% of Emergency Department • 48% of critical care admissions

  7. Introduction • 2003 Poison Center exposures • Increases fatality ratio • Greatest among those 80 years or older • May be grossly underestimated

  8. Introduction • The elderly are prescribed more drugs • 32% of prescriptions • Cardiovascular disease • Arthritis • Gastrointestinal disorders • Bladder dysfunction

  9. Introduction • Average use for persons 65 years or older: • 2 to 6 prescription drugs and 1 to 3.4 over-the-counter medicines • Average American senior spends $670/year for pharmaceuticals

  10. Polypharmacy • Polypharmacy means "many drugs“ • The use of more medication than is clinically indicated or warranted • 5 or more drugs

  11. Adverse Drug Reaction • The most consistent risk factor for adverse drug reactions (ADRs) is the number of drugs being taken • Risk rises exponentially as the number of drugs increases

  12. Adverse Drug Reaction ADRs occur as a result of • Drug-drug interactions • Drug-disease interactions • Drug-food interactions • Drug side effects • Drug toxicity

  13. Polypharmacy • Polypharmacy leads to: • More adverse drug reactions • Patient outcomes • Poor quality of life • High rate of symptomatology • (Unnecessary) drug exposure/expense

  14. Consequences: Quality of Life • In ambulatory elderly: 35% experience ADRs and 29% require medical intervention • In nursing facilities: 2/3 of residents experience ADRs • Up to 30% of elderly hospital admissions involve ADRs *Beers MH. Arch Internal Med. 2003

  15. “If medication related problems were ranked as a disease, it would be the fifth leading cause of death in the US!” *Beers MH. Arch Internal Med. 2003

  16. Pharmacokinetics and Aging • Absorption • Distribution • Metabolism • Excretion

  17. Pharmacokinetics and Aging • Absorption: • Age-related gastrointestinal tract and skin changes seem to be of minor clinical significance for medication usage

  18. Pharmacokinetics and Aging • Distribution: • Important Age-Related Changes: • Decrease in Lean Body Mass and total body water • Increased percentage Body Fat

  19. Pharmacokinetics and Aging • Increase in volume of distribution for lipophilic drugs • Protein Binding changes are of modest significance for most drugs, especially at steady-state

  20. Volume of distribution (Vd) • Apparent volume the drug is dissolved in • Measured in Liters or Liters/Kg • not a real volume

  21. Pharmacokinetics and Aging • Metabolism: • Though liver function tests are unchanged with age, there is some overall decline in metabolic capacity • Decreased liver mass and hepatic blood flow

  22. Pharmacokinetics and Aging • Hepatic conjugation • Inactive metabolites • Hepatic oxidation • Active metabolites

  23. Pharmacokinetics and Aging • Renal Excretion: • Age-related decreased renal blood flow and GFR is well-established • Decreased lean body mass leads to decreased creatinine production

  24. Pharmacokinetics and Aging Cr clearance=(140-age)(IBW)/creatinine(72) (multiply by 0.85 for women) Example: “70kg” 75 year old man Cr Clearance= (140-75)(70)/1.0(72)=63

  25. Pharmacodynamics and Aging • Generally, lower drug doses are required to achieve the same effect with advancing age • Receptor numbers, affinity, or post-receptor cellular effects may change • Changes in homeostatic mechanisms can increase or decrease drug sensitivity

  26. Avoiding Polypharmamcy • Avoid automatic refills • Look for other sources of medications ie. OTC • Caution with multiple providers • Don’t use medications to treat side effects of other meds • What can you discontinue or substitute for safer medication?

  27. Vitamin and Herbal Use in Older Adults • Highly prevalent among older adults • Generally not reported to the physician • Some serious drug interactions are possible: • Warfarin: gingko biloba, vitamin E • SSRI’s: St. Johns Wort

  28. (Potentially)Inappropriate Medications for Older Adults * • Propoxephene • Diphenhydramine • Amitryptiline • Alprazolam • Diazepam * Beers, MH et al. Arch Intern Med 151:1825,1991.

  29. Polypharmacy in the Making… • Drug reactions in the elderly often produce effects that simulate the conventional image of growing old: unsteadiness drowsiness dizziness falls confusion depression nervousness incontinence fatigue malaise insomnia

  30. Polypharmacy in the Making… • Avoid treating adverse reactions/side effects of drug with more drugs! • Dizziness from anti-hypertensive treated with meclizine • Edema from a calcium-channel blocker treated with furosemide and KCL

  31. Polypharmacy in the Making… • Drugs most frequently associated with adverse reactions in the elderly: • psychotropic drugs • anti-hypertensive agents • diuretics • digoxin

  32. Polypharmacy in the Making… • NSAIDS • corticosteroids • warfarin • theophylline

  33. Warfarin • Drugs that inhibit warfarin's metabolism include ciprofloxacin (Cipro), clarithromycin (Biaxin), erythromycin, metronidazole (Flagyl) and trimethoprim-sulfamethoxazole (Bactrim, Septra) • Acetaminophen

  34. Warfarin • Aspirin • Nonsteroidal Anti-inflammatory Drugs

  35. Fluoroquinolones • Divalent cations (calcium and magnesium) and trivalent cations (aluminum and ferrous sulfate)

  36. Antiepileptic Drugs • Carbamazepine (Tegretol), phenobarbital and phenytoin (Dilantin) • CYP450 interactions

  37. Fluoxetine (Prozac)Paroxetine (Paxil)Sertraline (Zoloft) Cimetidine (Tagamet)Clarithromycin (Biaxin)ErythromycinFluvoxamine (Luvox)Grapefruit juiceItraconazole (Sporanox)Ketoconazole (Nizoral)Lovastatin (Mevacor)Nefazodone (Serzone)Cisapride (Propulsid) 2D6/3A4

  38. Lithium • Diuretics • Ace Inhibitors • NSAIDS

  39. Sildenafil • Nitrates

  40. 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors • Concomitant use of statins and erythromycin, itraconazole, niacin or gemfibrozil (Lopid) can cause toxicity that manifests as elevated serum transaminase levels, myopathy, rhabdomyolysis and acute renal failure

  41. Serotonergic Agents • Inhibit 5-HT uptake • Enhances 5-HT release • Inhibits 5-HT breakdown • Metabolized to 5-HT • 5-HT1A agonist • Enhances 5-HTreceptor response to stimulation

  42. Case 1 80 year old widow who now lives with her daughter comes to Emergency Department complaining of being a nervous wreck and not being able to “turn off her mind for the past 2 yrs”. She brings with her a bag of all her meds

  43. Case 1 PMHx: CHF, irritable bowel syndrome, depression, HTN, recurrent UTIs, stress incontinence, anemia, occipital headaches, osteoarthritis, generalized weakness

  44. Case 1 Meds: sucralfate, Cimetidine, enteric ASA, Atenolol, Digoxin, Alprazolam, Naproxen, Oxybutynin, Dicyclomine TID, Lasix, Tylenol #2, Verapramil

  45. Medication Red Flags: • High risk drugs: alprazolam, oxybutynin, tylenol #2, dicyclomine, NSAIDS • Digoxin

  46. P-Glycoproteins, Digoxin and polypharmacy Small Intestine Biliary Excretion * * Bile Hepatocyte Plasma Lumen Enterocyte Plasma Renal Tubular Secretion * Urine Tubular Cell Plasma

  47. Inhibitors Amiodarone Clarithromycin Cyclosporine Diltiazem Erythromycin Ketocanazole Quinidine Verapramil tacrolimus Inducers Rifampin St. John’s Wort Dexamethasone Indinavir Ritonavir Retonoic acid Morphine Phenothiazine clotrimazole P-Glycoproteins

  48. Medication Red Flags: • naproxen and aspirin carry the potential drug related adverse events of gastritis/GIB and sucralfate and cimetidine are being used to treat these side effects

  49. Case 2 Mrs. Jones is a 72 yr living in an assisted living facility where she has been recently complaining of increasing confusion, lightheadedness in the am and difficulty sleeping at night

  50. Case 2 PMHx: CHF, NIDDM, OA, glaucoma, depression, and stress incontinence Meds: Digoxin, Furosemide, Timolol gtts, Metformin, Ibuprofen, Paroxetine, Oxybutynin,Propoxyphene/apapprn, and Diphenhydramine

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