Janet Cho PharmD CGP Clinical Pharmacist Keck Medical Center of USC Bradley R Williams PharmD FASCP CGP Professor Clinical Pharmacy amp Clinical Gerontology Prescription Medication Use ID: 1011668
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1. Pharmacotherapy in Older Adults Janet Cho, PharmD, CGPClinical Pharmacist, Keck Medical Center of USCBradley R. Williams, PharmD, FASCP, CGPProfessor, Clinical Pharmacy & Clinical Gerontology
2. Prescription Medication UseGu Q, et al., NCHS Data Brief No. 42, 2010
3. Why Are We Concerned?Older adults account for 49.8% of hospital admissions due to adverse drug events1Rate is greatest for age 85+ years87% due to hypoglycemics, anticonvulsants, warfarin, digoxin, theophylline, lithiumAdults age 50+ account for 51.1% of ED admissions for adverse drug events2CNS drugs (28.8%), blood modifiers (22.6%), cardiovascular meds (18.1%) are most common1Budnitz, et al, JAMA, 2006; 2The DAWN Report, 2011
4. Why Are We Concerned?Medicare hospital readmissions130 days (19.6%); 60 days (28.2%)Heart failure, pneumonia, COPD, psychosis are most common discharge diagnosesPreventable medication errors2Renal and hepatic functionDrug interactionsLack of individualized therapy1 Jencks, et al., NEJM, 2009; 2 Kohn, et al. Institute of Medicine, 2000
5. Physiologic changes affect both pharmacokinetics and pharmacodynamicsReduced physiologic reserve narrows the margin for errorPolymedicine increases the risk for adverse reactions and drug interactionsMultiple providers and self-care both increase the risk for inappropriate medication useAge-associated Issues
6. Physiologic ChangesBody compositionIncrease in body fat (% of total body weight)Women: 33% to 48%Men: 18% to 36%Decrease in body waterReduced serum albuminIncreased α1-acid glycoproteinDecreased lean body mass
7. Physiologic ChangesGastrointestinal tractIncreased gastric pHReduced intestinal blood flowImpaired active & passive transport mechanismsDelayed gastric emptyingSlowed GI motility
8. Physiologic ChangesLiverDecreased hepatic massReduced hepatic blood flowKidneyLoss of functioning nephronsReduced renal blood flowDecreased tubular secretionDecreased glomerular filtration
9. Drug AbsorptionPrimarily a passive process that occurs in the small intestineRate of absorption may be slowedDelayed, lower peak serum levelsIncreased bioavailability for some hepatically metabolized drugs due to reduced first-pass effect (e.g., verapamil, labetalol, lidocaine)Transdermal absorption is variable
10. Drug DistributionDecreasedLean body massTotal body waterSerum albuminCardiac outputIncreasedTotal body fatα1-acid glycoproteinFactors leading to altered distribution…
11. Drugs with Decreased BindingBenzodiazepinesDiazepamLorazepamTemazepamTriazolamDesipramineMeperidineNSAIDsDiflunisal*Naproxen*Salicylates*PhenytoinTheophyllineValproate*Warfarin* >50% decrease
12. Drug MetabolismReduced liver mass and volumeDecreased hepatic blood flowAltered enzyme activitySex and genetic differencesAge-associated declinesDrug interactionsNutrition and health statusFactors leading to altered metabolism…
13. Aging & CYP ActivityDecreasedDecreased or UnchangedUnchangedCYP 1A2CYP 2C19CYP 2ACYP 2C9CYP 3A4CYP 2D6-Cusack. Am J Geriatr Pharmacother 2004;2:274-302
14. Other InfluencesFactorResultSmokingInductionAlcoholInductionDrugsInduction/InhibitionDietVariableMalnutritionInhibition, if severeFrailtyInhibition-O’Mahoney & Woodhouse. Pharmacol Ther 1994;61:279-287
15. Drug Renal ExcretionReduced kidney mass, number and size of nephronsDecreased renal blood flowDecreased glomerular filtrationReduced tubular secretory mechanismsEffect of diseaseFactors leading to altered excretion…
16. CNS ChangesReduced blood flow and oxygenationIncreased MAO levelsDecreased norepinephrine, dopamineMore sensitive to sedating agentsGreater sensitivity to anticholinergic agentsIncreased permeability of the blood-brain barrier
17. Cardiovascular ChangesDecreased response to catecholaminesPrimarily affects ß-receptorsIncreased circulating norepinephrineReduced cardiac outputIncreased peripheral resistanceLess responsive baroreceptors
18. Pharmacogenomic IssuesNo apparent changes across the adult lifespanPossibly some decrease in CYP 3A4 and 2A6Fast and slow metabolizersN-acetyltransferase activitySlow acetylators (autosomal recessive)
19. Medication-related ProblemsDose too highDose too lowImproper medicationContraindicationAllergyInappropriate for patient’s age or functionDrug interactionAdverse drug reactionUnnecessary medicationDuplicateNo indicationProblem resolvedUntreated indicationPatient not receiving medication
20. Medication Risk Assessment> 5 medications> 12 daily dosesNarrow therapeutic index drugsMultiple prescribersTaking medicines for at least 3 problemsUses multiple pharmaciesSomeone brings medicines to the homeComplex regimenAt least 4 direction changes in 1 yearAny medicine taken for an unknown reason-Levy HB, Ann Pharmacother, 2003
21. High-risk PatientsMultiple diseasesComplex regimensDrug-disease interactionsMultiple drugsAdverse effectsDrug-drug interactionsFrailRisk for overdosageDepressedMultiple somatic complaintsNon-adherenceDementedUnreliable regarding adherence, adverse effects, etc.
22. SummaryAge-associated changes in pharmacokinetics and pharmacodynamics present therapeutic challengesInterpatient variability makes it difficult to predict clinical effects with certaintyDisease, nutrition, adherence, other drugs complicate the picturePatients benefit from a “risk management” approach