7/2/2012

Polypharmacy & Pitfalls in Prescribing for your Older Adults

Internal Medicine July 18, 2012
Jeff Wallace, MD, MPH Professor of Medicine, Division of Geriatrics University of Colorado School of Medicine

Polypharmacy & Pitfalls: Talk Objectives

Describe relevant pharmacokinetic & pharmacodynamic s that occur w/aging Identify medications that frequently cause problems in the elderly Learn and apply approaches to reduce polypharmacy in older adults

Pharmacodynamics
Response that occurs when a drug interacts at its receptor

Pharmacodynamic Changes with Aging

Increased response
Opiates Warfarin

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Pharmacodynamic Changes with Aging

Pharmacokinetics
Drug concentration at the site of action

Increased response
Opiates Warfarin

Decreased response
Beta-agonists

Pharmacokinetics
Drug concentration at the site of action 4 Determinants:
Absorption

Pharmacokinetic Changes with Aging

Absorption
gastric pH gastric emptying splanchnic blood flow intestinal motility

Distribution
Metabolism

Minimal clinical importance

Elimination

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Pharmacokinetic Changes with Aging

Distribution
fat mass muscle mass total body water albumin (binds acidic drugs) alpha-1 glycoprotein (binds basic drugs)

Effects of Aging on Volume of Distribution: Muscle and Fat mass s

64 yr old woman

Cross-section CT Thighs

Clinically important

20 yr old woman
J Nutr 1997 127:990S

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)
American Geriatrics Society GRS6 Teaching Slides

Pharmacokinetic Changes with Aging

Metabolism
hepatic mass hepatic blood flow first-pass metabolism

Clinical importance - marginal

concentration & half-life of drugs undergoing Phase I metabolism

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Pharmacokinetic Changes with Aging

Elimination
renal mass, renal blood flow glomerular filtration rate (10 cc/decade)

CG vs MDRD (Modification of Diet in Renal Dz)

Verhave et al
Mean age (yrs) Mean measured GFR (ml/min/1.73m2) Subject characteristics CG MDRD 71 79.4

Lamb et al
80 53.3

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

Healthy no DM, CAD, CHF, CRI

Comorbidities and CRI

Underestimated GFR Underestimated GFR Underestimated GFR Overestimated GFR

Talk Objectives
Describe relevant pharmacokinetic & pharmacodynamic s that occur w/aging Identify medications that frequently cause problems in the elderly Learn and apply approaches to reduce polypharmacy in older adults

Prescribing in the Elderly: Drugs to avoid?

Hx: 83 yo F with DM (A1C 7.2% on glipizide) & HTN (well controlled w/HCTZ) presents with dysuria & frequency. Low grade fever, no chills, no n/v. NKDA. Exam: T 1000F 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

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Drug Prescribing in the Elderly

The Beers List of Potentially Inappropriate rxes in older adults

Which of the following is the least appropriate choice for empiric tx of her UTI? A. Cephalexin B. Nitrofurantoin C. TMP/SMX D. Levafloxacin

First generation antihistamines (eg, diphenhydramine) GI antispasmodics (eg, hyoscyamine) Muscle relaxants Benzodiazepines Nonbenzodiapine sleepers: avoid use > 90 days Tertiary TCAs (eg, amitriptyline, doxepin > 6mg) Chronic use non-COX selective NSAIDS (unless other
rxs 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 pts

Muscle 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 in Older Adults. J Am Geriatr Soc 2012:60:616-31

One of the first duties of the physician is to 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 witnessed syncopal event while seated shortly after eating dinner. 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 - sinus bradycardia, HR often in 40s on ED monitor.

Its the Drugs!: Include in every Diff Dx

Medication Issues
Assuming his syncope is med related, the most 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, 1.11.6) Dose effect: donepezil > 10mg 2.1 risk
J Am Geriatr Soc 2009;57:1997

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)
Arch Intern Med 2009;169:867

Was it in your bradycardia differential diagnosis?

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Elderly Bear Burden of Injuries from Rxs

Emergency Hospitalizations for Adverse Drug 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% insulins 14% - oral antiplatelet drugs 13% - oral hypoglycemics 11%

ADEs are responsible for 5% - 28% of acute geriatric hospital admissions Can we identify common offending meds?

high risk meds implicated in only 1% of admits

NEJM 2011;365:2002-12

American Geriatrics Society GRS6 Teaching Slides

Polypharmacy and the Elderly

12% of the population aged 65+ 30% of all prescription drug use among those aged 65+ 50% of all OTC drug use is among pts 65+

Adverse Drug Reactions

106,000 deaths in 1994 (5th 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 Between Polypharmacy and ADRs

Percent of Patients with an ADR

Talk Objectives
Describe relevant pharmacokinetic & pharmacodynamic s that occur w/aging Identify medications that frequently cause problems in the elderly Learn and apply approaches to reduce polypharmacy in older adults

# of Drugs Taken
L Nolan, JAGS, 1988; 36: 142-9.

Plus prescribing tips in the elderly

Reducing Polypharmacy

Optimizing Therapies and Care Plans

Recognize opportunities to stop meds

As long-term management of multiple comorbid chronic diseases among an increasingly older population becomes the face of modern medicine, disentangling adverse drug events will become more blurred by the growing epidemic of polypharmacy. This remains a challenge to be appropriately addressed.
Editorial re: Dabigatran and bleeding concerns in elderly Arch Intern Med 2012;172:403

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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Use of EBM to Optimize Care of the Elderly

Apply clinical practice guidelines with caution
Almost all existing guidelines have single dz focus

EBM to Optimize Care of the Elderly

Apply clinical practice guidelines with caution
CHF Guidelines: based on excellent RCT data Issue: Older Adults w/CHF often w/comorbid dz

Application of CPGs to hypothetical 79yo pt w/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

Characteristics 2.5 million Medicare Beneficiaries Hospitalized 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

EBM for the Frail Older Adult

Does the Emperor have any clothes?

Reducing Polypharmacy
Tools to identify potentially inappropriate meds

Evidence for the best care of frail older pts w/multimorbidity is often lacking "Absence of evidence is not evidence of absence" -Carl Sagan, Astronomer (and Donald Rumsfeld)

Beers Criteria
J Am Geriatr Soc 2012:60:616-31

STOPP/START
Int J Clin Pharmacol Ther 2008;46:72

Good Palliative-Geriatric Practice Algorithm

Arch Intern Med Oct 2010;170:1648

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Reducing Polypharmacy in the Elderly

Good Palliative-Geriatric Practice Algorithm

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 rxs 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

Arch Intern Med Oct 2010;170:1648

Prescribing Tips in the Elderly

The Prescribing cascade

Avoid the Prescribing Cascade

Drug 1
Adverse effect misinterpreted as new medical condition

Avoiding drug-drug interactions

Be aware of non-adherence Patient education MD Education: Know what your pt is taking

Drug 2
PA Rochon, BMJ, 1997; 315:1096-9.

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Avoid the Prescribing Cascade

HCTZ Allopurinol NSAIDs Antihypertensives

Prudent Prescribing: Beware of Drug-Drug Interactions

100% chance of DDI with 8 drugs Nearly 50% of community-dwelling geriatric patients had at least one DDI DDI can result in ADRs or suboptimal dosing A key: Avoid Polypharmacy

Metoclopramide Carbidopa/Levodopa
Cholinesterase inhibitors Tolterodine

Relation Between Polypharmacy and Compliance

% Compliance

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

# of Drugs Prescribed

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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

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

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 Arch Intern Med 2006;166:1829

Do you know whats in your patients medicine cabinet?

The Knowledge Factor

~20% of drugs found on home inventory were not revealed by physician interview
Most frequently unreported class of drugs?

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The Knowledge Factor

20% of drugs found on home inventory were not revealed by physician interview
Most frequently unreported class of drugs?

BENZODIAZEPINES!!!

How can we improve our knowledge of patient drug use?

Before Prescribing New Med Consider:

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?
AGS GRS6 Teaching Slides

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