Geriatric Pharmacotherapy

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Geriatric Pharmacotherapy. Objectives. Understand key issues in geriatric pharmacotherapy Understand the effect age on pharmacokinetics and pharmacodynamics Discuss risk factors for adverse drug events and ways to diminish them Understand the principles of drug prescribing for older patients. - PowerPoint PPT Presentation

Text of Geriatric Pharmacotherapy

  • Geriatric Pharmacotherapy

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

  • The Aging ImperativePersons aged 65y and older constitute 13% of the population and purchase 33% of all prescription medications

    By 2040, 25% of the population will purchase 50% of all prescription drugs

  • Challenges of Geriatric PharmacotherapyNew drugs available each yearFDA approved and off-label indications are expandingAdvanced understanding of drug-drug interactionsIncreasing popularity of nutriceuticalsPolypharmacyMedication complianceEffects of aging physiology on drug therapyMedication cost

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

  • Age-related changes which affect pharmacokinetics

    decreased lean body massaffects drug distributiondecreased levels of serum albuminaffects drug distributiondecreased liver functionaffects drug metabolism/biotransformationdecreased renal functionaffects drug elimination

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

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

  • Factors Affecting AbsorptionRoute of administrationWhat it taken with the drugDivalent cations (Ca, Mg, Fe)Food, enteral feedingsDrugs that influence gastric pHDrugs that promote or delay GI motilityIncreased GI pHDecreased gastric emptyingDysphagia

  • Effects of Aging on Volume of Distribution (Vd)

    Aging EffectVd EffectExamples body water Vd for hydrophilic drugsethanol, lithium lean body mass Vd for for drugs that bind to muscledigoxin fat stores Vd for lipophilic drugsdiazepam, trazodone plasma protein (albumin) % of unbound or free drug (active)diazepam, valproic acid, phenytoin, warfarin plasma protein (1-acid glycoprotein) % of unbound or free drug (active)quinidine, propranolol, erythromycin, amitriptyline

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

  • Metabolic Pathways** NOTE: Medications undergoing Phase II hepatic metabolism are generally preferred in the elderly due to inactive metabolites (no accumulation)

    PathwayEffectExamplesPhase I: oxidation, hydroxylation, dealkylation, reductionConversion to metabolites of lesser, equal, or greaterdiazepam, quinidine, piroxicam, theophyllinePhase II: glucuronidation, conjugation, or acetylationConversion to inactive metaboliteslorazepam, oxazepam, temazepam

  • enzymatic reactions preparing drugs for elimination Phase I reactions:oxidation: catalyzed by cytochrome P450 enzymesPhase II reactions:conjugation: addition of small chemical groups which increase solubility to facilitate elimination

    decrease in hepatic blood flow often associated with decreased First Pass EffectPhase I metabolism decreasedPhase II metabolism generally preserved

  • Other Factors Affecting Drug MetabolismGenderSmokingDietDrug interactionsRaceWeakness

  • Concepts in Drug EliminationHalf-lifetime for serum concentration of drug to decline by 50% (expressed in hours)Clearancevolume of serum from which the drug is removed per unit of time (mL/min or L/hr)

  • Drug elimination changes in the elderlydecrease in renal functionsdecreased blood flow to the kidneysdecreased glomerular filtrationdecreased tubular secretiondecline in creatinine clearance

    Reduced elimination drug accumulation and toxicity

  • Effects of Aging on the KidneyDecreased 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 ElderlyCreatinine clearance (CrCl) is used to estimate glomerular rateSerum 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

  • Example: Creatinine Clearance vs. Age in a 55, 55 kg Woman

  • 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 SummaryPK 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 PharmacotherapyBalance between overprescribing and underprescribingCorrect drugCorrect doseTargets appropriate conditionIs appropriate for the patient

    Avoid a pill for every illAlways consider non-pharmacologic therapy

  • Consequences of OverprescribingAdverse drug events (ADEs)Drug interactionsDuplication of drug therapyDecreased quality of lifeUnnecessary cost

  • Adverse Drug Events (ADEs)Responsible for 5-28% of acute geriatric hospital admissionsGreater than 95% of ADEs in the elderly are considered predictable and approximately 50% are considered preventableMost errors occur at the ordering and monitoring stages

  • Most Common Medications Associated with ADEs in the Elderly

    Opioid analgesicsNSAIDsAnticholinergicsBenzodiazepinesAlso: cardiovascular agents, CNS agents, and musculoskeletal agents

    Adverse Drug Reaction Risk Factors in Older Outpatients. Am J Ger Pharmacotherapy 2003;1(2):82-89.

  • The Criteria

    High Potential for Severe ADEHigh Potential for Less Severe ADEamitriptylinechlorpropamidedigoxin >0.125mg/ddisopyramideGI antispasmodicsmeperidinemethyldopapentazocineticlopidineantihistamines diphenhydraminedipyridamoleergot mesyloidsindomethacinmuscle relaxants

  • Patient Risk Factors for ADEsPolypharmacyMultiple co-morbid conditionsPrior adverse drug eventLow body weight or body mass indexAge > 85 yearsEstimated CrCl
  • Drug-Drug Interactions (DDIs)May lead to adverse drug eventsLikelihood as number of medications Most common DDIs:cardiovascular drugspsychotropic drugsMost common drug interaction effects:confusion cognitive impairmenthypotensionacute renal failure

  • 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

  • Common Drug-Drug InteractionsDoucet J, Chassagne P, Trivalle C, et al. Drug-drug interactions related to hospital admissions in older adults: a prospective study of 1000 patients. J Am Geriatr Soc 1996;44(9):944-948.

    CombinationRiskACE inhibitor + potassiumHyperkalemiaACE inhibitor + K sparing diureticHyperkalemia, hypotensionDigoxin + antiarrhythmicBradycardia, arrhythmiaDigoxin + diureticAntiarrhythmic + diureticElectrolyte imbalance; arrhythmiaDiuretic + diureticElectrolyte imbalance; dehydrationBenzodiazepine + antidepressantBenzodiazepine + antipsychoticSedation; confusion; fallsNitrate/vasodilator/diureticHypotension

  • Drug-Disease InteractionsObesity 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 worsen a medical condition

  • Common Drug-Disease Interactions

    CombinationRiskNSAIDs + CHFThiazolidinediones + CHFFluid retention; CHF exacerbationBPH + anticholinergicsUrinary retentionNarcotics + constipationAnticholinergics + constipationExacerbation of constipationMetformin + CHFHypoxia; increased risk of lactic acidosisNSAIDs + gastropathyIncreased ulcer and bleeding riskNSAIDs + HTNFluid retention; decreased effectiveness of diuretics

  • Principles of Prescribing in the ElderlyAvoid 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 AppropriatelyDetermine 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

  • Preventing PolypharmacyReview medications regularly and each time a new medi