Geriatric Pharmacotherapy - Copy

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  • Objectives Understand key issues in geriatric pharmacotherapyUnderstand the effect age on pharmacokinetics and pharmacodynamicsDiscuss risk factors for adverse drug events and ways to mitigate themUnderstand the principles of drug prescribing for older patients

  • Challenges of Geriatric Pharmacotherapy New drugs available each yearFDA approved and off-label indications are expandingChanging managed-care formulariesAdvanced understanding of drug-drug interactionsIncreasing popularity of nutriceuticalsMultiple co-morbid statesPolypharmacyMedication complianceEffects of aging physiology on drug therapyMedication cost

  • Pharmacokinetics (PK) Absorption bioavailability: the fraction of a drug dose reaching the systemic circulationDistribution locations in the body a drug penetrates expressed as volume per weight (e.g. L/kg)Metabolism drug conversion to alternate compounds which may be pharmacologically active or inactiveElimination a drugs final route(s) of exit from the body expressed in terms of half-life or clearance

  • Effects of Aging on Absorption Rate of absorption may be delayedLower peak concentrationDelayed time to peak concentrationOverall amount absorbed (bioavailability) is unchanged

  • Hepatic First-Pass Metabolism For drugs with extensive first-pass metabolism, bioavailability may increase because less drug is extracted by the liverDecreased liver massDecreased liver blood flow

  • Factors Affecting Absorption Route of administrationWhat it taken with the drug -Divalent cations (Ca, Mg, Fe) - Food, enteral feedings - Drugs that influence gastric pH - Drugs that promote or delay GI motilityComorbid conditionsIncreased GI pHDecreased gastric emptyingDysphagia

  • Aging Effects on Hepatic Metabolism Metabolic clearance of drugs by the liver may be reduced due to: - decreased hepatic blood flow - decreased liver size and massExamples: morphine, meperidine, metoprolol, propranolol, verapamil, amitryptyline, nortriptyline

  • Other Factors Affecting Drug Metabolism GenderComorbid conditionsSmokingDietDrug interactionsRaceFrailty

  • Concepts in Drug Elimination Half-life - time for serum concentration of drug to decline by 50% (expressed in hours)Clearance - volume of serum from which the drug is removed per unit of time (mL/min or L/hr)Reduced elimination drug accumulation and toxicity

  • Effects of Aging on the Kidney Decreased kidney sizeDecreased renal blood flowDecreased number of functional nephronsDecreased tubular secretionResult: glomerular filtration rate (GFR)Decreased drug clearance: atenolol, gabapentin, H2 blockers, digoxin, allopurinol, quinolones

  • Estimating GFR in the Elderly Creatinine clearance (CrCl) is used to estimate glomerular rate Serum creatinine alone not accurate in the elderly - lean body mass lower creatinine production - glomerular filtration rateSerum creatinine stays in normal range, masking change in creatinine clearance

  • Pharmacodynamics (PD) Definition: the time course and intensity of pharmacologic effect of a drugAge-related changes: sensitivity to sedation and psychomotor impairment with benzodiazepines level and duration of pain relief with narcotic agents drowsiness and lateral sway with alcohol HR response to beta-blockers sensitivity to anti-cholinergic agents cardiac sensitivity to digoxin

  • PK and PD Summary PK and PD changes generally result in decreased clearance and increased sensitivity to medications in older adultsUse of lower doses, longer intervals, slower titration are helpful in decreasing the risk of drug intolerance and toxicityCareful monitoring is necessary to ensure successful outcomes

  • Optimal Pharmacotherapy Balance between overprescribing and underprescribingCorrect drugCorrect doseTargets appropriate conditionIs appropriate for the patientAvoid a pill for every illAlways consider non-pharmacologic therapy

  • Consequences of Overprescribing Adverse drug events (ADEs)Drug interactionsDuplication of drug therapyDecreased quality of lifeUnnecessary costMedication non-adherence

  • Most Common Medications Associated with ADEs in the Elderly Opioid analgesicsNSAIDsAnticholinergicsBenzodiazepinesAlso: cardiovascular agents, CNS agents, and musculoskeletal agents

  • Patient Risk Factors for ADEs PolypharmacyMultiple co-morbid conditionsPrior adverse drug eventLow body weight or body mass indexAge > 85 yearsEstimated CrCl
  • Concepts in Drug-Drug InteractionsAbsorption may be or Drugs with similar effects can result additive effectsDrugs with opposite effects can antagonize each otherDrug metabolism may be inhibited or induced

  • Drug-Disease Interactions Obesity alters Vd of lipophilic drugsAscites alters Vd of hydrophilic drugsDementia may sensitivity, induce paradoxical reactions to drugs with CNS or anticholinergic activityRenal or hepatic impairment may impair metabolism and excretions of drugsDrugs may exacerbate a medical condition

  • Principles of Prescribing in the Elderly Avoid prescribing prior to diagnosisStart with a low dose and titrate slowlyAvoid starting 2 agents at the same timeReach therapeutic dose before switching or adding agentsConsider non-pharmacologic agents

  • Prescribing Appropriately Determine therapeutic endpoints and plan for assessmentConsider risk vs. benefitAvoid prescribing to treat side effect of another drugUse 1 medication to treat 2 conditionsConsider drug-drug and drug-disease interactionsUse simplest regimen possibleAdjust doses for renal and hepatic impairmentAvoid therapeutic duplicationUse least expensive alternative

  • Summary Successful pharmacotherapy means using the correct drug at the correct dose for the correct indication in an individual patientAge alters PK and PDADEs are common among the elderlyRisk of ADEs can be minimized by appropriate prescribing