2/11/2016
Managing Polypharmacy: Evidence-based Dissection of Pharmaceuticals
Heather Veeder MD Medical Director – VITAS Healthcare San Antonio, TX Adjunct Professor of Medicine University of Texas Health Science Center San Antonio [email protected]
Disclosure
I have no relevant financial relationships to disclose.
Objectives
To understand polypharmacy: its prevalence, causes, and outcomes
To be able to better assess the pharmaceutical profile of patients
To develop a process by which pharmaceutical profiles can be modified to contain the most appropriate medications for each patient
1 2/11/2016
Agenda
Definition and Prevalence
Causes
Effects and Outcomes
Pharmacokinetics and Pharmacodynamics
Tools
Polypharmacy – Definition(s)
Medications used concurrently or excessively
More medications than are indicated for a specific problem – consider ALL medications, preparations, lotions, potions, nutraceuticals regardless of source
More than a specific number
Threshold ≥ 5
Excessive ≥ 10
Polypharmacy – Definition
Consider the appropriateness of the medication regimen
Was the medication once appropriate → Is the medication still appropriate?
Is the medication still clinically indicated?
Does anyone (patient, family, clinician) know why the medication is being taken?
Is the medication effective – either by patient report or in literature?
Is the medication duplicative?
2 2/11/2016
Prevalence
Polypharmacy is more common than expected
Multiple statistics from multiple sources
1998-99: 25% of US population took >5 medications; 5% > 10
2005-6: 29% took >5 meds
20-35% of community-dwelling elders took > 10 meds
>40% of elderly hospital inpatients were taking at least 1 inappropriate medication; of these, 33% lacked indication
Agenda
Definition and Prevalence
Causes
Effects and Outcomes
Pharmacokinetics and Pharmacodynamics
Tools
Causes – Patient Factors
Age
Population is aging and acquiring more medical conditions
More medical conditions = More medical interventions
Add treatments for primary and secondary prevention
40-48 yo: 18% polypharmacy prevalence
80-89 yo: 78% polypharmacy prevalence
3 2/11/2016
Causes – Patient Factors
Self-medication
33% of people >75 yo take ≥ 3 OTC daily
Analgesics
Nutritional supplements, vitamins, complementary medications
Interventions touted online, Dr. Oz, infomercials
Causes – Patient Factors
Sharing medications – “this helps me, so maybe it will help you”
Expectation that everything can be made better by a pharmaceutical
“better living through chemistry”
Antibiotics for viral infections
Causes – Physician Factors
Tyranny of Evidence Evidence-based quality measures must be followed
Physicians tracked and rated on these measures Reimbursement will be tied to measures and outcomes
HTN – ACE and ARBs
DM – HbA1c < 7 Guidelines
Each focuses on one disease process Multiple conditions → Multiple guidelines → Multiple medications However… not tested on elderly Following multiple guidelines can harm rather than benefit the patient
4 2/11/2016
Causes – Physician Factors
Medicalization
Every symptom MUST be treated with a medication
Ex: terminal secretions with anticholinergics
Expectation that every patient/physician encounter MUST end with a prescription
“the doctor didn’t do anything for me”
Using antibiotics to treat viral syndromes
Unnecessary analgesics/opioids
Causes – Physician Factors
Medication Cascade Prescription of Drug A → Side Effect 1 Side Effect 1 seen as new symptom or disease Drug B Prescribed → Side Effect 2 Side Effect 2 seen as another new symptom or disease Drug C Prescribed → Side Effect 3…
Consider any new symptom in a patient to be a medication side effect until proven otherwise Consider stopping an existing medication rather than prescribing a new one
Causes – Physician Factors
Physician Behavior
Physicians tend not to take a full medication history – limits information
Physicians lack knowledge of side effects
Professional courtesy
Physicians often reluctant to change orders of another physician
“There had a be some reason the medication was prescribed.”
5 2/11/2016
Causes – Physician Factors
Fragmentation of Healthcare Infrastructure
Multiple transitions with different clinicians at each stage
Often no one physician knows the patient’s narrative
Multiple providers → Lack of continuity
Multiple providers may use different pharmacies → duplicate medications
Agenda
Definition and Prevalence
Causes
Effects and Outcomes
Pharmacokinetics and Pharmacodynamics
Tools
Effects of Polypharmacy
Decrease in physical and cognitive function
The greater the number of medications taken (≥ 5), the greater the decrease in function.
Age-matched populations:
Fewer medications: 30% had decreased function in IADLs
Five or more medications: 75% had decreased function in IADLs
Decrease in function/IADLs → Decrease in independence
Progression to loss of ADLs → greater assistance required → losses for the person; increased caregiver responsibility; caregiver burnout; increased financial burden on person, caregiver, system
6 2/11/2016
Effects of Polypharmacy
Delirium – when a patient becomes delirious, look at the medication list first
Falls – increased risk with psychotropic or cardiovascular medications
Decreased Nutrition
Medications cause anorexia, nausea, dry mouth
Medications cause increased appetite with increase in non-nutritious intake
Effects of Polypharmacy
Adverse Drug Events
When inappropriate medications are prescribed, the risk of ADE outweighs potential clinical benefits
When multiple medications are prescribed, the risk for drug-drug interactions also increases
More medications = More chances for adverse events or errors
Effects of Polypharmacy
7 2/11/2016
Effects of Polypharmacy
Errors lead to: Emergency Department visits Acute care hospital admissions Premature stoppage of drug Need for more medications Deterioration of underlying disease Non-adherence Falls – injury is 5th leading cause of death, many due to falls Cognitive decline Death
Agenda
Definition and Prevalence
Causes
Effects and Outcomes
Pharmacokinetics and Pharmacodynamics
Tools
Pharmacokinetics & Pharmacodynamics
Aging associated with changes in body and organ function:
DNA damage due to lifetime of oxidative stress
Telomere shortening
Changes in gene expression
Up-regulation of cell apoptosis
Studies of drug effects do not account for these changes
Elderly and debilitated usually excluded from trials
Test subjects for efficacy trials for life expectancy of decades
8 2/11/2016
Pharmacokinetics
Absorption
Decreased due to decreased GI blood flow, GI motility, gastric emptying, gastric acid production
First pass effect also decreased due to decreased liver mass
Distribution
Altered protein binding
Increase in α-1-acid glycoprotein (CA, inflammation)
More binding = less free drug (β-blockers)
Decrease in albumin
Less binding = more free drug (warfarin)
Pharmacokinetics
Liver size decreases by 1/3, hepatic blood flow decreases by 40% = decreased metabolism of β–blockers, Ca-channel blockers, TCAs
Cytochrome P450 decreased = prolonged metabolic clearance (alprazolam)
Excretion
Kidney size decrease by 20-30%
Effects of disease (CKD)
Prolonged clearance
Pharmacodynamics
Cardiovascular Medications
Ca-channel blockers – increased hypotensive effect without rebound tachycardia
Think: FALLS
Decreased baroreceptor sensitivity
Think: FALLS
Loop diuretics less effective
9 2/11/2016
Pharmacodynamics
CNS Medications
Increased sensitivity to benzodiazepines, atypical antipsychotics
Underlying alterations of receptors in brain:
Dopamine, GABA, NMDA
Lead to increased risk of sedation, extrapyramidal signs, confusion, insomnia, falls
Pharmacodynamics
Medications that prolong QT interval
increased risk of torsades de pointes and V. fib
Antipsychotics, antiarrhythmics, antidepressants, antihistamines, antibiotics…
Hypoglcemia
Keeping HbA1c < 7 increases risk of falls
Multiple hypoglycemic episodes lead to worsening of cognitive impairment
Sulfonylureas are secretagogues
Can accumulate in renal insufficiency with increased risk of hypoglycemia
Agenda
Definition and Prevalence
Causes
Effects and Outcomes
Pharmacokinetics and Pharmacodynamics
Tools
10 2/11/2016
Medication Review
Should be done at regular intervals, especially with any transition of care
Goal: the right medications – not too many, not too few
Patient comorbidities
Patient goals of care
Patient preferences
Patient ability to adhere to regimen
Medication Review
“Brown Bag Review”
“Bring me everything you put into or onto your body to treat something, make you feel better, or prevent something.”
What are patients really taking and how?
Not just asking about medications
Medication Review
Beware the trap of Ageism
>75% of elders have capacity
>80% of elders understand their medications
Falls, confusion, and lethargy are not part of normal aging
Match everything in the brown bag to a diagnosis or symptom
Look for overtreatment – what is there – expected/unexpected?
Look for undertreatment – what is missing?
Look for orphan drugs – what are they doing there?
11 2/11/2016
Medication Review
Review for adherence – how often do you miss taking a dose of your medications?
Review for Adverse Drug Effects
Any new symptom in an elder should/could be considered a drug side-effect until proven otherwise
Patients often do not relate ADRs to the medication, as symptoms may not start for weeks after starting
May need to describe symptoms to patients, families
Medications to Think About
Warfarin/Other Anticoagulants
One-year risk of CVA in a fib decreased from 4% to 2%
Risk of intracranial or GI bleed 8% in debilitated patients
Risk further increased with frequent falls
Statins
How much more benefit does patient with limited life span derive from lipid control?
How much increased debility from muscle pain or weakness?
Medications to Think About
Clopidogrel
Evidence exists for up to 6 months of treatment after stent placement
NNT for 2 years to prevent 1 CVA = 200
Furosemide
Best indication in stable heart failure
Risk: decreased renal blood flow, increased dehydration, falls
12 2/11/2016
Medications to Think About
No added benefit for use beyond 3-5 years
Adherence: can patient remain upright for 30 minutes?
Donepezil
Clinically marginal increase in congnition
Side effects: nausea, anorexia, syncope
Medications to Think About
Sulfonylureas – glimepiride, glipizide
Secretagogues; can cause occult hypoglycemia
Increase in cognitive impairment, delirium, dizziness, falls
Vitamins E, A, β-carotene
Can cause fatigue, weakness, bleeding (vit E)
Associated with increase in all-cause mortality
Large pills
Medications to Think About
Antihypertensives
Is patient frail? No evidence of association between blood pressure control and mortality
Psychotropic medications (benzodiazepines, TCAs, SSRIs)
Increased confusion, increased falls
13 2/11/2016
“Sharp Dissection of Pharmaceuticals” ABCD Method – Glenn Ross
A Medications = must have medications
Medications necessary for symptom control
Patient should remain on these
Plan = continue
B Medications = nice to have medications
Medications currently necessary for symptom control but need to be reviewed on regular basis
Oral medications that do not have parenteral form
Medications with limited efficacy as patient declines
Plan = continue for now
“Sharp Dissection of Pharmaceuticals” ABCD Method – Glenn Ross
C Medications – why is this here?
Medications with no known indication or resolved condition
Medications used inappropriately or for wrong indication
Medications which are no longer effective
Medications which are duplicative
Medications used for primary or secondary prevention following guidelines that no longer apply to the patient
Medications that increase anticholinergic or serotonergic burden
Plan = develop a process to discontinue medications safely and in an orderly fashion
“Sharp Dissection of Pharmaceuticals” ABCD Method – Glenn Ross
D Medications – oh no!
Medications which are harmful to the patient or place the patient at high risk of severe complications
Medications which need to be stopped quickly
Plan = discontinue medications as quickly and safely as possible
14 2/11/2016
Discontinuing Medications: Deprescribing
Less is more
Discontinuing Medications: Deprescribing
Start low, go slow Use judgment Plan to discontinue on mediation at a time Stop abruptly or taper as the medication dictates Monitor for side effects:
Withdrawal symptoms Reappearance of previous symptoms
Worsening of underlying condition If adverse reaction appears, restart medication and move on If no adverse reaction appears, move on
Discontinuing Medications: Deprescribing
Study of Nursing Home Residents
Discontinuation of medications provoked no adverse reactions
Only 10% of medications had to be restarted
Study of Community-Dwelling Elders
Mean number of medications stopped per patient: 5
66% of patients had all planned medications stopped
Only 2% of those medications had to be restarted
With appropriate information, consultation, critical thinking, and planning, deprescribing can be successful.
15 2/11/2016
Discontinuing Medications
Check out Bohemian Polypharmacy (by James McCormack, PharmD; [email protected])
https://www.youtube.com/watch?v=Lp3pFjKoZl8
References
Allen R. 10 drugs to reconsider when a patient enrolls in hospice. Newsline, National Hospice and Palliative Care Organization online. May 2014. American Geriatrics Society 2012 Beers Criteria Update Expert Panel. AGS updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2012; 60:616-631. Bain KT, Holmes HM, Beers MA, et al. Discontinuing medications: a novel approach for revising the prescribing stage of medication use process. J Am Geriatr Soc 2008; 56:1946-1952. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. Arch Intern Med 1997; 157:1531-1536. Garfinkel D, Mangin D. Feasibility study of a systemic approach for discontinuation of multiple medications in older adults. Arch Intern Med 2010; 170:1648-1654.
References
Hanlon JT, Semla TS, Schmader KE. Medication misadventures in older adults: literature from 2013. J Am Geriatr Soc 2014; 62:1950-1953. Holmes HM. Rational prescribing for patients with a reduced life-expectancy. Clin Pharmacol Ther 2009; 85:103-107. Holmes HM, Sachs GA, Shega JW, et al. Integrating palliative medicine into the care of persons with advanced dementia: identifying appropriate medication use. J Am Geriatr Soc 2008; 56:1306-1311. Hovstadius B, Petersson G. Factors leading to excessive polypharmacy. Clin Geriatr Med 2012; 28;159-172. Scott IA, Gray LC, Martin JH, et al. Deciding when to stop: towards evidence-based deprescribing of drugs in older patients. Evid Based Med 2013; 18:121-14. Sera LC, McPherson ML. Pharmacokinetics and pharmacodynamic changes associated with aging and implications for drug therapy. Clin Geriatr Med Clin 2012; 28:273-286.
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References
Shah BM, Hajjar ER. Polypharmacy, adverse drug reactions and geriatric syndromes. Clin Geriatr Med Clin 2012; 28:173-186. Shi S, Morike K, Klotz U. Clinical implications of ageing for rational drug therapy. Eur J Clin Pharmacol 2008; 64:183-199. Steinman MA, Hanlon JT. Managing medications in clinically complex elders. JAMA 2010; 304:1592-1601. Tamura BK, Bell CL, Inaba M, et al. Outcomes of polypharmacy in nursing home residents. Clin Geriatr Med Clin 2012; 28:217-236. Thompson AM, Linneber SA, Vande Griend JP, et al. Glycemic targets and medication limits for type 2 diabetes mellitus in the older adult. Consult Pharm 2014;293:110- 123. Woodward MC. Deprescribing: achieving better health outcomes for older people through reducing medications. J Pharm Prac Res 2003; 33:323-328.
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