690 likes | 1.13k Views
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
E N D
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 • Outline pharmacokinetics as it relates to the aging population
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
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
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
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
Introduction • 2003 Poison Center exposures • Increases fatality ratio • Greatest among those 80 years or older • May be grossly underestimated
Introduction • The elderly are prescribed more drugs • 32% of prescriptions • Cardiovascular disease • Arthritis • Gastrointestinal disorders • Bladder dysfunction
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
Polypharmacy • Polypharmacy means "many drugs“ • The use of more medication than is clinically indicated or warranted • 5 or more drugs
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
Adverse Drug Reaction ADRs occur as a result of • Drug-drug interactions • Drug-disease interactions • Drug-food interactions • Drug side effects • Drug toxicity
Polypharmacy • Polypharmacy leads to: • More adverse drug reactions • Patient outcomes • Poor quality of life • High rate of symptomatology • (Unnecessary) drug exposure/expense
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
“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
Pharmacokinetics and Aging • Absorption • Distribution • Metabolism • Excretion
Pharmacokinetics and Aging • Absorption: • Age-related gastrointestinal tract and skin changes seem to be of minor clinical significance for medication usage
Pharmacokinetics and Aging • Distribution: • Important Age-Related Changes: • Decrease in Lean Body Mass and total body water • Increased percentage Body Fat
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
Volume of distribution (Vd) • Apparent volume the drug is dissolved in • Measured in Liters or Liters/Kg • not a real volume
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
Pharmacokinetics and Aging • Hepatic conjugation • Inactive metabolites • Hepatic oxidation • Active metabolites
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
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
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
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?
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
(Potentially)Inappropriate Medications for Older Adults * • Propoxephene • Diphenhydramine • Amitryptiline • Alprazolam • Diazepam * Beers, MH et al. Arch Intern Med 151:1825,1991.
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
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
Polypharmacy in the Making… • Drugs most frequently associated with adverse reactions in the elderly: • psychotropic drugs • anti-hypertensive agents • diuretics • digoxin
Polypharmacy in the Making… • NSAIDS • corticosteroids • warfarin • theophylline
Warfarin • Drugs that inhibit warfarin's metabolism include ciprofloxacin (Cipro), clarithromycin (Biaxin), erythromycin, metronidazole (Flagyl) and trimethoprim-sulfamethoxazole (Bactrim, Septra) • Acetaminophen
Warfarin • Aspirin • Nonsteroidal Anti-inflammatory Drugs
Fluoroquinolones • Divalent cations (calcium and magnesium) and trivalent cations (aluminum and ferrous sulfate)
Antiepileptic Drugs • Carbamazepine (Tegretol), phenobarbital and phenytoin (Dilantin) • CYP450 interactions
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
Lithium • Diuretics • Ace Inhibitors • NSAIDS
Sildenafil • Nitrates
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
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
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
Case 1 PMHx: CHF, irritable bowel syndrome, depression, HTN, recurrent UTIs, stress incontinence, anemia, occipital headaches, osteoarthritis, generalized weakness
Case 1 Meds: sucralfate, Cimetidine, enteric ASA, Atenolol, Digoxin, Alprazolam, Naproxen, Oxybutynin, Dicyclomine TID, Lasix, Tylenol #2, Verapramil
Medication Red Flags: • High risk drugs: alprazolam, oxybutynin, tylenol #2, dicyclomine, NSAIDS • Digoxin
P-Glycoproteins, Digoxin and polypharmacy Small Intestine Biliary Excretion * * Bile Hepatocyte Plasma Lumen Enterocyte Plasma Renal Tubular Secretion * Urine Tubular Cell Plasma
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
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
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
Case 2 PMHx: CHF, NIDDM, OA, glaucoma, depression, and stress incontinence Meds: Digoxin, Furosemide, Timolol gtts, Metformin, Ibuprofen, Paroxetine, Oxybutynin,Propoxyphene/apapprn, and Diphenhydramine