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Lynsey E. Brandt, MD, PharmD
Christiana Care
Geriatrics Consult Program
April 15, 2016
Geriatrics Consult Program Lynsey Brandt, MD, PharmD
Located at Wilmington Hospital
Gateway Building, 5th floor
Scheduling: 302-320-6475
Falls Polypharmacy Medical Complexity Weight loss/ failure to
thrive Delirium Depression/ Anxiety Insomnia, Urinary
Incontinence, or Fatigue Need for Increased
Social Support Driving Concerns Goals of Care
Learning Objectives
Review risk of adverse drug events in older adults
Summarize pharmacokinetic & pharmacodynamic changes with age
Review drug interactions
Learning Objectives
List classes of medications with increased risk in older adults Beers List
Others
Discuss medication safety at transitions of care
Review the “Prescribing Cascade”
Take-Home Points Older adults are at risk for adverse drug events
Consider risk/ benefit for all medications (i.e. Beers list)
Beware of the prescribing cascade
“Start Low & Go Slow!”
I. Challenges of Prescribing for Older Adults
• Multiple chronic medical problems
• Multiple medications and prescribers
• Different metabolism and responses
• Adherence and cost
• Supplements, herbals, and OTC drugs
Lancet. 1995;346(8966):32–36.
ADR/ADE--defined
Adverse Drug Reaction (ADR)
any undesirable or noxious drug effect at standard drug treatment doses
WHO;1996 Technical Report Series No. 425
Adverse Drug Event (ADE)
ADRs + errors in drug administration
CHAMP. University of Chicago.
Adverse Drug Reactions Older adults 7 times more likely to have unwanted
side effect and 2-3 times more likely to have
ADRs
Multiple meds is the factor most strongly correlated with increased risk of ADRs
Exponential increase in ADRs with addition of more drugs to a regimen (2 drugs-15%, 5 drugs-50-60% )
ADE’s are Preventable
27.6% of adverse events were preventable
58.4% of these were associated with errors in prescribing
Gurwitz et al, JAMA 2003;289:1107-1116
II. Pharmacokinetics in Older Adults
Pharmacokinetics = “what the body does to the drug”
Absorption
Distribution
Metabolism
Excretion
Absorption
Overall absorption is unchanged by aging
Can be altered by drug interactions (i.e. calcium , iron)
Altered absorption of drugs in patients receiving enteral feeds
Distribution Less water
Less muscle
More fat
Lower plasma protein binding with age
Distribution Less water
Lower volume of distribution for water-soluble drugs (i.e. digoxin, lithium)
Less muscle
More fat
Accumulation of fat-soluble drugs, prolonging elimination and effect (i.e. diazepam)
Lower plasma protein binding with age
Increased free fraction of drug (i.e. warfarin)
Metabolism Reduced hepatic mass and blood flow leads to slower
metabolism
Excretion Renal function declines with age
Renal mass declines by 20-25% from age 30 to 80
Glomerular Filtration Rate decreases by 10% per decade of life after age 30
Excretion (cont.) Do not be misled by “normal” serum creatinine.
Adjust dose when creat clearance < 60
Calculate creatinine clearance using the Cockroft-Gault equation:
(140-age in years) x (Ideal body wt) x 0.85 (females)
72 (serum creatinine in mg/ dL)
Drugs with renal elimination (selected examples)
Allopurinol Antibiotics - Aminoglycosides
- Fluoroquinolones - Penicillins - Tetracyclines - Sulfa - Nitrofurantoin!!!
Digoxin
Furosemide Gabapentin H2 antagonists - Cimetidine - Famotidine - Ranitidine
Lithium Metformin
Pharmacodynamics “What the drug does to the body.”
Receptor responses vary with age
Beta adrenergic receptors: decreased sensitivity with age
CNS (increased blood brain barrier permeability, decreased cerebral blood flow)
Blunted baroreceptor reflex
Less predictable & often altered drug response at usual or lower concentrations
Central Nervous System Effects
Increased sensitivity to medications that affect the CNS
Symptoms: delirium, sedation, depression, confusion
Always start at low dose, and titrate slowly.
Anticholinergics
Antidepressants
Antihistamines
Analgesics
Benzodiazepines
Neuroleptics
Digoxin
Anticonvulsants
Anticholinergic properties frequently overlooked:
Elavil (amitriptyline) Flexeril (cyclobenzaprine)
Cogentin (benztropine) Atarax/Vistaril(hydroxyzine)
Bentyl (dicyclomine) Welbutrin/Zyban (bupropion)
Ditropan (oxybutynin) Antivert (meclizine)
Detrol (tolterodine) Ipratropium (atrovent)
Benadryl (diphenhydramine) Phenergan (promethazine)
Levsin (hyoscyamine) Atropine
Quinidine
3 factors to consider for ALL prescriptions: Allergies
Renal function
Drug interactions!
Safe-Prescribing Survey
Garbutt JM, et al. Acad Med. 2005 Jun;80(6):594-9.
Drug/ Drug Drug/ Disease Interactions
85 yo woman with history of CHF, admitted for a fall & CHF exacerbation.
PMH: CKD (GFR 40ml/min), Atrial Fibrillation, CHF, Diabetes
Develops right knee pain & swelling on 2nd hospital day
Aspiration of synovial fluid shows uric acid crystals.
Medication list: Lasix 40 mg qd
Coumadin 5 mg qd
Toprol xl 50 qd
Glipizide 5 mg qd
Case (cont.) Which of the following would you give for this patient:
a.) Indomethacin 50 mg TID
b.) Colchicine 0.6 mg BID
c.) Prednisone 60 mg QD
d.) Allopurinol 300 mg QD
e.) None of the above
Drug- disease interactions a.) Indomethacin 50 mg TID (CKD/ CHF)
b.) Colchicine 0.6 mg BID (CKD – renal dosing!)
c.) Prednisone 60 mg QD (DM)
d.) Allopurinol 300 mg QD (CKD- renal dosing!)
e.) None of the above
Drug-Disease Interactions Confusion benzodiazepines or anticholinergics
Bladder outlet obstruction anticholinergics, TCAs, antispasmodics, antihistamines
CKD, CHF, PUD NSAIDS
Constipation anticholinergics, TCAs, calcium channel blockers
Falls TCAs, benzodiazepines, SSRIs, antihypertensives
Fick DM Arch Intern Med 2003;163:2716-2724
Beers MH Arch Intern Med 1997;157:1531-1536
Drug-disease interactions
Key is to be aware of these potential interactions
Select the therapeutic plan with best benefit/ risk ratio.
Case (cont) On hospital day 4, patient develops low-grade temps
and dysuria.
UA shows 5-10 wbc, +leuk esterase, +nitrites
Urine culture with >100,000 E Coli, pan-sensitive
Patient has no known drug allergies
Case 2 (cont). Which antibiotic is the best choice for this patient:
a.) Bactrim DS -1 tab po BID x 3 days
b.) Bactrim DS- 1 tab po BID x 7 days
c.) Cipro 500 mg po BID x 7 days
d.) Amoxicillin 250 TID x 7 days
e.) Macrobid – 1 tab BID x 3 days
Case 2 (cont.) Which antibiotic is the best choice for this patient:
a.) Bactrim DS -1 tab po BID x 3 days
b.) Bactrim DS- 1 tab po BID x 7 days
c.) Cipro 500 mg po BID x 7 days
d.) Amoxicillin 250 TID x 7 days
e.) Macrobid – 1 tab BID x 3 days
Cytochrome P450 Systems
CYP3A Metabolizes >60% of prescribed drugs including:
Calcium channel blockers, certain beta-blockers, most “statins”, warfarin, amiodarone
CYP2D6 Metabolizes:
metoprolol, propranolol, tramadol, codeine,oxycodone,TCAs, SSRIs
Cytochrome P450 Inhibitors
CYP3A Inhibitors
Amiodarone, cimetadine, cyclosporin, erythromycin, itra-/ketoconazole, grapefruit juice
CYP2D6 Inhibitors
Cimetidine, SSRIs, quinidine
Strategies to check for drug interactions
Micromedex
Epocrates
The pharmacist!!
III. Potentially inappropriate meds
Sensitivity to CNS -active agents
Sedative- hypnotic meds associated with increased risk of:
Falls
Hip fractures
Delirium
Beers list
The Beers List List of drugs which are potentially inappropriate in the
elderly
Developed by consensus panel of geriatricians in 1991
Used by regulators to evaluate nursing home medication lists
The Beers List (selected examples)
Drug Reason Alternative
Antihistamines- 1st
generation
(diphenhydramine)
Anticholinergic
effects
Nonsedating
antihistamines
(loratadine)
Long-acting
benzodiazepines
(diazepam)
Sedation Short-acting
benzodiazepines
(lorazepam)
Narcotics (meperidine) Active metabolite Morphine
Hypoglycemic agents
(chlorpropamide)
Long half-life,
renally excreted,
risk of
hypoglycemia
Shorter-acting
agents (glipizide)
Other high-risk medications Study of 177.504 ER visits for adverse drug events
33% of the visits were due to:
Digoxin
Warfarin
Insulin
(“DWI”)
Drugs on the Beers list accounted for only 3.6% of visits
Budnitz et al. Annals of Internal Medicine. December 4, 2007 vol. 147
no. 11 755-765
IV. Medication Safety/ Transitions of Care
Home
ER
MICU
General Medical Ward
Rehab
Home!
“Too Many Cooks….”
Transitions of Care
Patients are vulnerable to experience medication problems at each “handoff”
Active vs. Passive role of patient
Problems with transitions: What the literature shows 20% incidence of adverse drug events (hospital to
home)
Patients’ limited recall of discharge instructions
Problems with adherence
Frequency of errors of discharge medication lists
Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.
Posthospital Medication Discrepancies
Looked at discrepancy between pre-hospital med lists, post-hospital med lists, and what the patients actually were taking.
Pts admitted with 1 of 9 selected conditions
Home visit 24 to 72 hours post-discharge
Prevalence & type of med discrepancies categorized
Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.
Posthospital Medication Discrepancies
14.1% of pts had at least 1 med discrepancy
51% patient-associated; 49% system-associated
5 med classes accounted for half of all discrepancies
Med discrepancies associated with total # of meds & presence of CHF
Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.
Posthospital Medication Discrepancies
Risk of Rehospitalization within 30 days!!! 14.3% of those with med discrepancies
rehospitalized
vs.
6.1% of those without a discrepancy (p=.04)
Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.
Strategies for improving medication safety at transitions What strategies do you utilize??
Recommendations
Obtain & review med bottles from home
Separate those that no longer using.
Compare pre-hospitalization meds with current list
Contact PCP and/or pharmacy
Verbally reconcile meds with pt/ caregiver (USE “TEACH BACK TECHNIQUE”)
Kackman, et al. Medication Reconciliation for Older Adults Transitioning from Long-Term Care to Home. Annals of Long-Term Care. August 2011.
Part V. Case example 85 yo man referred to PM&R for evaluation and
management of lumbar stenosis.
Exam: significant spasm of paraspinal muscles & EMG suggestive of radiculopathy.
He was prescribed gabapentin and diazepam.
Case example (cont) Two weeks later, the patient was seen by his Primary
MD because of visual hallucinations. Laboratory evaluation & head CT were unremarkable. Risperidone was prescribed.
While out of town one month later, patient developed tremors and a shuffling gait, and was taken to an urgent-care center. He was diagnosed with Parkinson’s and sinemet therapy was initiated….
Prescribing Cascade
Geriatrics Review Syllabus
Take-Home Points Older adults are at risk for adverse drug events
Consider risk/ benefit for all medications (i.e. Beers list)
Medication-related problems at transitions of care are associated with increased rate of readmissions
Beware of the prescribing cascade
“Start Low & Go Slow!
Geriatrics Consult Program Lynsey Brandt, MD, PharmD
Located at Wilmington Hospital
Gateway Building, 5th floor
Scheduling: 302-320-6475
Falls Polypharmacy Medical Complexity Weight loss/ failure to
thrive Delirium Depression/ Anxiety Insomnia, Urinary
Incontinence, or Fatigue Need for Increased
Social Support Driving Concerns Goals of Care