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Polypharmacy & Pitfalls inPrescribing for your Older Adults
Internal MedicineJuly 18, 2012
Jeff Wallace, MD, MPHProfessor of Medicine, Division of GeriatricsUniversity of Colorado School of Medicine
Polypharmacy & Pitfalls: Talk Objectives
Describe relevant pharmacokinetic &pharmacodynamic s that occur w/aging
Identify medications that frequently causeproblems in the elderly
Learn and apply approaches to reducepolypharmacy in older adults
Pharmacodynamics
Response that occurs when a druginteracts at its receptor
Pharmacodynamic Changes with Aging
Increased response Opiates Warfarin
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Pharmacodynamic Changes with Aging
Increased response Opiates Warfarin
Decreased response Beta-agonists
Pharmacokinetics
Drug concentration at the site of action
Pharmacokinetics
Drug concentration at the site of action
4 Determinants: Absorption Distribution Metabolism Elimination
Pharmacokinetic Changes with Aging
Absorption gastric pH gastric emptying splanchnic blood flow intestinal motility
Minimal clinical importance
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Pharmacokinetic Changes with Aging Elimination
renal mass, renal blood flow glomerular filtration rate (10 cc/decade)
Most clinically important concentration of drugs dependent on renal
clearance Serum creatinine alone does not provide
adequate information to guide dosing Use Cockcroft-Gault (CG) to estimate GFR in
older adults
CG vs MDRD ( Modification of Diet in Renal Dz)Verhave et al Lamb et al
Mean age (yrs) 71 80
Mean measuredGFR(ml/min/1.73m 2)
79.4 53.3
Subjectcharacteristics
Healthy no DM,CAD, CHF, CRI
Comorbidities andCRI
CG Underestimated GFR Underestimated GFR
MDRD Underestimated GFR Overestimated GFR
Talk Objectives
Describe relevant pharmacokinetic &pharmacodynamic s that occur w/aging
Identify medications that frequently causeproblems in the elderly
Learn and apply approaches to reducepolypharmacy in older adults
Hx : 83 yo F with DM (A1C 7.2% on glipizide) &HTN (well controlled w/HCTZ) presents withdysuria & frequency. Low grade fever, nochills, no n/v. NKDA.
Exam : T 100 0F BP 136/78 HR 88 Wt 55kg
Mild low abdominal discomfort to palpation, (-)CVAT, o/w unremarkable
Labs : U/A 10-30 WBC, nitrate (+), electrolytes nl,Bun/Cr 24/1.3
Prescribing in the Elderly: Drugs to avoid?
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Drug Prescribing in the Elderly
Which of the following is the least appropriatechoice for empiric tx of her UTI?
A. Cephalexin
B. Nitrofurantoin
C. TMP/SMX
D. Levafloxacin
The Beers List of PotentiallyInappropriate rx es in older adults First generation antihistamines (eg, diphenhydramine)GI antispasmodics (eg, hyoscyamine)Muscle relaxantsBenzodiazepinesNonbenzodiapine sleepers: avoid use > 90 daysTertiary TCAs (eg, amitriptyline, doxepin > 6mg)Chronic use non-COX selective NSAIDS (unless otherrxs not effective & pt can take gastroprotection rx)
Digoxin > 0.125mg
Central alpha agonists (eg, clonidine)J Am Geriatr Soc 2012:60:616-31
Three Meds I hate to see in older ptsMuscle relaxants
Sedating, anticholinergic, falls/fx , ?able efficacy
Iron more than once daily (or w/PPIs) Marginal gain BID/TID iron, adverse GI effects H+ absorption
Megestrol acetate (Megace) minimal effect on wt, takes months, thrombotic
events, possibly death
Beers Criteria for Potentially Inappropriate Medication Use inOlder Adults. J Am Geriatr Soc 2012:60:616-31
One of the first duties of the physician isto educate the masses not to take medicine - Sir William Osler
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When to Just Say No
NSAIDS - other than short-term use PPIs avoid chronic use Benzodiazepines Sedating antihistamines 1st generation tricyclics Iron > 325mg/d Muscle relaxants
A Case of Syncope A 79 yo M w/HTN, dementia, stage IV CKD,
restless legs & OA presents to ED s/p witnessedsyncopal event while seated shortly after eatingdinner. He denies CP or SOB.
Meds: amlodipine 5mg, hctz 25mg, donepezil 10mg,sinemet 25/100 qhs, tylenol & tramadol prn.
VS are 134/76, HR 52 supine, 128/72 & 54 standing.Exam is o/w unremarkable. EKG - sinusbradycardia, HR often in 40s on ED monitor.
Medication Issues
Assuming his syncope is med related, themost likely medication implicated is :
A. Donepezil
B. Amlodipine
C. Sinemet
D. Tramadol
E. HCTZ
Cholinesterase inhibitors and bradycardia ChE-I RR bradycardia 1.4 (95% CI, 1.1 1.6) Dose effect: donepezil > 10mg 2.1 risk
Clinical significance: ChE-I use associated with Syncope: HR 1.76 (95% CI, 1.57-1.98)
ED visits for bradycardia: HR 1.69 Pacemaker placement: HR 1.49 Hip Fx: HR 1.18 (95% CI, 1.03-1.34)
Was it in your bradycardia differential diagnosis?
Its the Drugs!: Include in every Diff Dx
J Am Geriatr Soc 2009;57:1997
Arch Intern Med 2009;169:867
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Elderly Bear Burden of Injuries from Rxs
American Geriatrics Society GRS6 Teaching Slides
ADEs are responsible for 5% - 28% of acutegeriatric hospital admissions
Can we identify common offending meds?
Emergency Hospitalizations for AdverseDrug Events (ADEs) in Older Americans
National electronic ADE surveillance 2007-09
Hospitalization rates after ED visits for ADEs
Pts age 65+ had 100,000 admits/yr
Four meds/classes causes 2/3 of the mayhem Warfarin 33% - oral antiplatelet drugs 13% insulins 14% - oral hypoglycemics 11%
high risk meds implicated in only 1% of admits
NEJM 2011;365:2002-12
Polypharmacy and the Elderly12% of the population aged 65+
30% of all prescription druguse among those aged 65+
50% of all OTC druguse is among pts 65+
Adverse Drug Reactions
106,000 deaths in 1994 (5 th leading cause death)
$177 billion in 2000
For every $1 spent on drugs, $1 spent on ADRs
7-fold increased risk in the elderly Changes in pharmacodynamics/kinetics Drug-disease and drug-drug interactions Related to Polypharmacy
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Exponential Relation BetweenPolypharmacy and ADRs
L Nolan, JAGS, 1988; 36: 142-9.
# of Drugs Taken
P e r c e n t o f
P a t
i e n t s
w i t h a n
A D R
Talk Objectives
Describe relevant pharmacokinetic &pharmacodynamic s that occur w/aging
Identify medications that frequently causeproblems in the elderly
Learn and apply approaches to reducepolypharmacy in older adults
Plus prescribing tips in the elderly
Reducing PolypharmacyAs long -term management of multiplecomorbid chronic diseases among anincreasingly older population becomes theface of modern medicine, disentanglingadverse drug events will become moreblurred by the growing epidemic ofpolypharmacy. This remains a challenge tobe appropriately addressed.
Editorial re: Dabigatran and bleeding concerns in elderlyArch Intern Med 2012;172:403
Optimizing Therapies and Care Plans
Recognize opportunities to stop meds
Review existing meds before starting new rx
Annual/semiannual medication review
Care transitions are key opportunities
Is pt managing current care plan
Is complexity impacting adherence & safety
Have pt preferences changed?
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Apply clinical practice guidelines with caution
Almost all existing guidelines have single dz focus
Application of CPGs to hypothetical 79yo ptw/COPD, DM, HTN, OP, OA
12 medications, complicated regimen $406 monthly cost
Studies rarely include frail elderly, mult comorbid dz
Risks (drug-drug, drug-dz interactions) likely are
Do CPGs address short & long term goals?
Pt preferences?JAMA 2005;294:716
Use of EBM to Optimize Care of the Elderly EBM to Optimize Care of the Elderly Apply clinical practice guidelines with cautionCHF Guidelines: based on excellent RCT data
Issue: Older Adults w/CHF often w/comorbid dz
Characteristics 2.5 million Medicare BeneficiariesHospitalized for Heart Failure, 2001-2005
mean age 80 years old, nearly 60% women 2/3 of pts w/chronic atherosclerosis 67% HTN 42% COPD 42% diabetes mellitus each of these w/CPGs 30% renal failure 14% dementia
Arch Intern Med 2008;168(22):2481-8
Evidence for the best care of frail older ptsw/multimorbidity is often lacking
" Absence of evidence i s not evidence of absence " --Carl Sagan, Astronomer (and Donald Rumsfeld)
EBM for the Frail Older AdultDoes the Emperor have any clothes? Reducing Polypharmacy
Tools to identify potentially inappropriate meds
Beers Criteria
STOPP/START
Good Palliative- Geriatric Practice Algorithm
J Am Geriatr Soc 2012:60:616-31
Arch Intern Med Oct 2010;170:1648
Int J Clin Pharmacol Ther 2008;46:72
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Arch Intern Med Oct 2010;170:1648
Reducing Polypharmacy in the Elderly
Polypharmacy & inappropriate meds common
Results in compliance, D.I.s, ADEs
RCTs: Rx reviews by PharmDs 1 rx
Good Palliative -Geriatric Practice algorithm
NH: 3 rx s hosp (30 v 12%), mort (45 v 21%)
Outpt: n 70, x age 83, x 8 meds by 4, 19 mo f/u- 2% failed rx d/c, resumed d/t sxms, no M&M
Arch Intern Med Oct 2010;170:1648
Good Palliative -Geriatric Practice Algorithm
Prescribing Tips in the Elderly
The Prescribing cascade
Avoiding drug-drug interactions
Be aware of non-adherence
Patient education MD Education: Know what your pt is taking
Avoid the Prescribing Cascade
Drug 1
Adverse effectmisinterpreted as new
medical condition
Drug 2
PA Rochon, BMJ, 1997; 315:1096-9 .
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Avoid the Prescribing Cascade
HCTZ Allopurinol
NSAIDs Antihypertensives
Metoclopramide Carbidopa/Levodopa
Cholinesterase inhibitors Tolterodine
Prudent Prescribing:Beware of Drug-Drug Interactions
100% chance of DDI with 8 drugs
Nearly 50% of community-dwelling geriatricpatients had at least one DDI
DDI can result in ADRs or suboptimal dosing
A key: Avoid Polypharmacy
Relation Between Polypharmacyand Compliance
# of Drugs Prescribed
% C o m p l
i a n c e
Improving Medication Compliance
Why arent pts more compliant? Compliance 50%, dramatically after 6 mo
Number of meds the key factor
Other potential factors lack of information/understanding
side-effects forgetfulness emotional factors costs
NEJM 2005;353:487
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Prudent Prescribing:Improving Medication Compliance
Explain why, what and when of any new rx MDs often fail in this regard
FP and IM docs observed for 243 new rxs never stated name of new med explicit directions, duration 50% of time
Write indication ON RX it will be on bottle! Lisinopril to improve heart function Metoprolol to help prevent heart attack
Arch Intern Med 2006;166:1855
Methods to Improve Compliance # of drugs, prescribers and pharmacies Once or twice daily dosing Pill boxes, medication reminder charts Pay attention to costs - 13% elderly w/cost
related non-adherence (gen not inform MD) frequency of clinic visits
Arch Intern Med 2006;166:1829
Do you know whats in yourpatients medicine cabinet? The Knowledge Factor
~20% of drugs found on home inventorywere not revealed by physician interview
Most frequently unreported class of drugs?
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The Knowledge Factor
20% of drugs found on home inventorywere not revealed by physician interview
Most frequently unreported class of drugs?
BENZODIAZEPINES!!!
How can we improve ourknowledge of patient drug use?
Is this medication necessary/non-pharm options?
What are the therapeutic end points?
Do the benefits outweigh the risks?
Is it used to treat effects of another drug?
Could it interact with diseases, other drugs? Consider compliance and cost challenges
Does patient know what its for, how to take it,and what ADEs to look for?
Before Prescribing New Med Consider:
AGS GRS6 Teaching Slides