Polypharmacy: More drugs, more problems! Edward L. Schneider, M.D. Dean Emeritus and Professor of Gerontology, Medicine and Biological Sciences University of Southern California Davis School of Gerontology
NY Times April 16, 2013 Elderly Pa8ents Rou8nely Prescribed Risky Drugs
• Doctors in the United States rou8nely prescribe poten8ally harmful drugs to older pa8ents, and the problem is par8cularly acute in the South, a new study shows. • So don’t get sick during this mee8ng!
Drug Side Effects are not new! • An 1814 ar8cle on arsenic in the New England Journal of Medicine on the treatment of “herpe8c affec8ons” • “the beneficial effects of the remedy are not apparent un8l aSer its use has been some8me discon8nued”
Jerry Avorn. Two Centuries of Assessing Drug Risks N Engl J Med 2012; 367:193-‐197 July 19, 2012
Case History • Mary Moore, a 82 year old woman, had been just released from the hospital for hypertension, heart failure and kidney failure. • Her prescrip8on for hydralazine to control her blood pressure was filled at a Jeffersontown, Kentucky pharmacy. • Instead of hydralazine, they gave her hydroxyzine, a centrally ac8ng an8-‐histamine. • She took the wrong medica8on for two weeks. Her blood pressure went off the charts and she was hospitalized and died. • The family is suing the pharmacy for wrongful death. • If one of your caregivers was managing the medica5ons of one of your residents, would they be able to detect this mistake? From Modern Maturity June 2012, pg 20.
America’s Love Affair with the Pill
Starts Early in Life
Wall Street Journal, 12/28/10, D1-‐2
• • • • • • • • • •
4 Billion Prescrip8ons in 2010 (78% were for generic drugs) Hydrocodone with acetominophen (Vicodin) 131 million Simvasta8n (Zocor) 94 million Lisinopril (Zestril) 87 million Levothyroxine (Synthyroid) 70 million Amlodipine (Norvasc) 57 million Omeprazole (Prilosec) 53 million Azithromycin (Zithromax) 52 million Amoxicillin 52 million Memormin (Glucophage) 48 million Hydrochlorothiazide 48 million
Americans Spent $307 billion on prescrip8on drugs in 2010 • • • • • • • • • •
Lipitor $7.2 billion Nexium $6.3 billion Plavix $6.1 billion Advair $4.7 billion Abilify $4.6 billion Seroquel $4.4 billion Singulair $3.6 billion Crestor $3.8 billion Actos $3.5 billion Epogen $3.3 billion
Some Facts about Prescrip8on Drug Use by Older Americans • Those 65 and older, 13% of the popula8on, use 1/3 of all prescrip8on medica8ons • Those 65 and older, consume 40% of all non-‐prescrip8on medica8ons • The more medica8ons a person takes, the greater the risk of non-‐compliance
Polypharmacy is not just about Prescrip8on Drugs • Your residents will be taking: – over-‐the-‐counter medica8ons – supplemental vitamins and minerals – herbal remedies
Examples of Adverse Drug Reac8ons Anaphylaxis from allergic response to almost any drug Delirium from many drugs including benzodiazepines Hypoglycemic shock from lnsulin Excessive bleeding from warfarin C. Difficile induced pseudomembranous coli8s from an8bio8c therapy • Gastrointes8nal bleeding from NSAIDs • • • • •
Adverse Drug Reac8ons (ADRs) • Each year, 175,000 older adults, ages 65 and above are seen in Emergency Dept’s due to ADRs • About 15% of hospitaliza8ons in those 65 and older are due to ADRs • 106,000/year die from an ADR. • Fatal ADRs rank fourth to sixth in leading causes of death
Why are there so many ADRs? • 2/3 of pa8ent visits to a physician result in the wri8ng of a new prescrip8on • ADRs increase exponen8ally with 4 or more prescrip8ons. • Pa8ents who take 8 or more medica8ons have a 90% chance of experiencing a medica8on-‐related problem
Why are there so many ADRs? • • • • • • • •
When you visit your internist/family physician, she orders medica8ons for you When you visit your cardiologist, she orders medica8ons for you When you visit your urologist, she orders medica8ons for you When you visit your endocrinologist, she orders medica8ons for you When you visit your gastroenterologist, she orders medica8ons for you When you visit your rheumatologist, she orders medica8ons for you When you visit your nephrologist, she orders medica8ons for you When you visit your pulmonologist, she orders medica8ons for you
But they do not usually take the /me to: • • • •
Review your medica8ons Communicate with each other Eliminate those medica8ons that are not necessary Eliminate those medica8ons that interact with each other
Medical Silos Medical Team
•
Why are there so many ADRs? Pharmokine/c changes with aging Gastrointes8nal absorp8on
decreases with aging • Liver metabolism of drugs changes with aging • Kidney secre8on of drugs changes with aging • Body fat increases and body water decreases The dosage of drugs need to be readjusted as we age!
Why are there so many ADRs? Pharmacodynamic Changes with Aging • Paradoxical response to Barbiturates • Increased sensi8vity to Coumadin • Increased sensi8vity to Digitalis • Increased sensi8vity to Verapamil • Increased sensi8vity to Benzodiazepines Start low and go slow!
Why are there so many ADRs? Drug-‐Drug Interac/ons • Impossible for a physician to know all the possible drug-‐drug interac8ons • Some common examples – Prescrip8on drugs with other prescrip8on drugs: Sta8ns and erythromycin and other an8bio8cs – Prescrip8on drugs with alterna8ve medica8ons: St. John’s Wort and mul8ple drugs – OTC drugs with prescrip8on drugs: An8cholinergic cold remedies and Phenothiazines, An8-‐Parkinson drugs and Oxybutrin (Ditropan) – Prescrip8on drugs interac8ng with OTC drugs, vitamins and alterna8ve medica8ons: Warfarin, NSAIDs, vitamin E and Ginkgo Biloba.
Prescrip8on Drug Interac8ons • • • • • •
Amiodarone and Quinolones, Simvasta8n Carbamazepine and Macrolides Digoxin and Macrolides Sta8ns and Azole An8fungals Tamoxifen and An8depressants Warfarin and NSAIDs, Sta8ns, Fibrates, Azole An8fungals and Carbamazepine
Interac7ons Between Prescrip7on Meds and Dietary Supplements
An8convulsants: Borage oil, evening primrose oil, shankapulshpi, bio8n, folate, vitamins B6 and D Barbiturates: Valerian Benzodiazepines: Valerian, kava root, grapefruit juice Bisphosphonates: Bonemeal, calcium, ipriflavone, iron, magnesium Cor8costeroids: Aloe latex, buckthorn bark and berry, cascara, fenugreek, licorice root, Ephedra, Echinacea, zinc Cyclosporine: St. John’s wort Digoxin Digitalis: Ephedra, guar gum, hawthorn, licorice root, pec/n, psyllium, kyushin, plantain, uzara root, ginseng, St. John’s wort Estrogens: Androstenedione, grapefruit juice, chasteberry, fenugreek, licorice root, Panax, ginseng, saw palmeCo, Siberian ginseng, Glitazones: Inositol, niacin Heparin: Goldenseal Insulin: Chromium, ginseng Iron: St. John’s wort, saw palmeto Lithium: Caffeine, coffee, guarana, psyllium Metoclopramide: Chasteberry Oral contracep8ves St. John’s wort Oral hypoglycemics: a-‐Lipoic acid, devil’s claw, Ephedra, fenugreek, feverfew, garlic, ginger, Gotu Kola, guar gum, horse chestnut seed, licorice root, Panax ginseng, psyllium, Siberian ginseng, s8nging netle, karela, inositol, niacin Proton pump inhibitors: Bonemeal, calcium, indole-‐3-‐carbinol, iron, vitamin B12 Spironolactone: Licorice SSRIs: St. John’s wort Sta8ns: Red yeast (Monascus), grapefruit juice, pec/n, coenzyme Q10, vitamin C Tetracycline: Calcium, iron, manganese, magnesium, pec8n Theophylline: Ipriflavone, vitamin B6
Thiazides: Ginkgo biloba Thyroid hormone: Bugleweed, red yeast, kelp, calcium, iron, bonemeal Warfarin: Garlic, Ginkgo biloba, devil’s claw, dong quai, Panax ginseng, vitamin E, feverfew, vitamin K, borage oil, Chlorella, coenzyme Q10, curcuminoids, evening, primrose oil, flaxseed oil, tocopherols, hemp seed oil, inositol, iodine, niacin, psyllium, 8ratricol, wheat and barley grass, chondroi8n
Drug-‐disease Interac8ons • Pa8ent with PD have increased risk of drug induced confusion • Urinary reten8on in BPH pa8ents on decongestant or an8cholinergic cold remedies • Cons8pa8on worsened by calcium supplements, an8cholinergics, calcium channel blockers • Neurolep8cs, tramadol, quinolones lower seizure thresholds
Example of the complexity of taking certain medica8ons: Fosamax for Osteoporosis • Take Fosamax in the morning when you get up • 30 minutes before you eat or drink anything • Then for the next 30 minutes do not eat or drink anything besides plain water • Don’t lie down.
Compliance with Prescrip8on Medica8ons
Wall Street Journal, R8, 3/28/11
Organizing your medica8ons
Organizing the Delivery of Medica8ons
Kathy Sitek with her son and husband developed a pill organizing system for herself
MicrosoS Applica8on
MyNetDiary App
Risk of ADR is 35 8mes higher if you are taking one of these: • Insulin for blood glucose control for diabetes • Digoxin for atrial fibrilla8on and/or conges8ve heart failure • Coumadin to prevent blood clots Why? of their narrow therapeu8c Because window: the small difference between the therapeu8c level and the toxic level.
Risk Factors for Adverse Events among Nursing Home residents • ADE were iden8fied in 410 nursing home residents • Case controlled • Prospec8ve study • 12 months Risk Factors for Adverse Drug Events Among Nursing Home Residents. Terry S. Field, Gurwitz JH, Avorn, J et. al. (2001) Arch Intern Med 161:1629-‐1634.
Independent Risk Factors for Having an Adverse Drug Event in a nursing home Risk Factor
Odds Ra7o (95% Confidence Int)
New Resident
2.8 (1.5-‐5.2)
No. of regularly scheduled meds <5
1.0 (Referent)
5-‐6
2.0 (1.2-‐3.2)
7-‐8
2.8 (1.7-‐4.7)
9 or more
3.3 (1.9-‐5.6)
An8bio8cs/an8-‐infec8ves
4.0 (2.5-‐6.2)
An8psycho8cs
3.2 (2.1-‐4.9)
An8depressants
1.5 (1.1-‐2.3)
Risk Factors for Adverse Drug Events Among Nursing Home Residents. Terry S. Field, Gurwitz JH, Avorn, J et. al. (2001) Arch Intern Med 161:1629-‐1634.
Most Common Adverse Drug Events in Nursing home Residents • • • • • •
Neuropsychiatric 28% Falls 13% Dermatologic 12% GI 11% Hemorrhage 11% Extrapyramidal 11%
Risk Factors for Adverse Drug Events Among Nursing Home Residents. Terry S. Field, Gurwitz JH, Avorn, J et. al. (2001) Arch Intern Med 161:1629-‐1634.
Beers’ List • • • •
Mark Beers , a geriatrician at UCLA criterua for poten8ally inappropriate medica8on use in older adults Updated in 2012 Lists classes of drugs and indicates which ones to avoid Printable pocket card: htp://www.americangeriatrics.org/files/documents/beers/ PrintableBeersPocketCard.pdf
This one
Atypical An8psycho8c Medica8ons Ariprazole (Ambilify) * Clozapine (Clozaril) Olanzapine (Zyprexa) Que8apine (Seroquel)* Risperidone (Risperdal) Ziprasdieone (Geodon)
*Top 10 sales of prescrip8on medica8ons in 2010
Atypical An8psycho8cs • Developed for treatment of psychosis • Approved by FDA for treatment of psychosis • Used frequently to treat behavioral problems in demented pa8ents • Not approved by the FDA to treat demen8a • Black Box warning issued by FDA for these medica8ons for increased risk of cardiovascular events and death • Very serious side effects: metabolic syndrome, extrapyramidal symptoms, somnolence, falls, cogni8ve impairment
Newcomer J. Second-‐genera8on (atypical) an8psycho8cs and metabolic effects: a comprehensive literature review. CNS Drugs. 2005, 19 Suppl 1:1-‐93.
Concluding Thoughts • The more medically complex residents you welcome, the more medica8ons they will be taking • The more medica8ons your residents take, the greater their risk of adverse drug responses and non-‐compliance • The more cogni8ve impairment they have, the greater the risk of non-‐compliance • Your challenge will be in organizing the delivery of these medica8ons and monitoring residents for side effects. • Your chances of successfully limi8ng adverse drug responses will be increased by having staff trained in gerontology and geriatrics • My course, GERO 510, an introduc8on to Geriatrics focuses on the common condi8ons of aging and the medica8ons that are used to treat these condi8ons.