Drug Interactions in Older Adults[老年人药物相互作用](PPT-33).ppt

Drug Interactions in Older Adults,Joseph T.Hanlon,PharmD,MS,Learning Objectives,At the conclusion of this talk the participant should be able to:List the 4 major types of drug interactions that can occur in the elderlyDiscuss the epidemiology of the different types of drug interactions in the elderlyImplement strategies to prevent/manage drug interactions in the elderly,Types of Drug Interactions,Drug-Drug PharmacokineticDrug-Drug PharmacodynamicDrug-Food/NutrientDrug-Disease,Drug-Drug Interactions Affecting Absorption and Distribution,Precipitant Drug(s)Object Drug(s)OutcomeAntacids,IronTetracycline,Ciprofloxacin abs.Chloral hydrateWarfarin PPBGenerally absorption and distribution drug-drug-interactions are not clinically important.Drugs 12:485-94,Hepatic Metabolism,Phase I(CYP 450)Oxidation hydroxylation dealkylation sulfoxidationReductionHydrolysis,Phase II Conjugation glucuronidation sulfation glycine acetylation,Cytochrome P450 Phase I Isoenzymes,%Total and Substrate Examples,Isoenzymes%SubstrateCYP1A217Olanzapine,TheophyllineCYP2C9/1926Phenytoin,WarfarinCYP2D62-4Codeine,Desipramine,TramadolCYP2E19-10Chlorzoxazone,EthanolCYP3A435-45Diazepam,Triazolam,Quinidine,Methadone,Carbamazepinewww.drug-,Inhibitors of Hepatic Cytochrome P450,1A2 2C9/19 2D6 3A4FluvoxamineAmiodaroneFluoxetineErythromycinCimetidineFluconazoleParoxetineAzole antifungalCiprofloxacinFluvastatinQuinidineNefazodoneFluoxetineRitonavirClarithromycinIsoniazidBupropionRitonavirSertralineCimetidineCimetidineOmeprazoleCimetidinewww.drug-,J Pharmacol Exp Ther 1997;280:627-37.,Effect of Age on Theophylline Hepatic Metabolism Inhibition,Drugs That Interact with Theophylline,InhibitorsCimetidinePropafenoneMexiletinePropranololErythromycinCiprofloxacinFluvoxamineDrugs Aging.2003;20:71-84,InducersBarbituratesPhenytoinSmokingRifampinCarbamazepineJAPHA 2004;44:142-51,Drug-Drug Interactions With Warfarin,Interacting DrugMechanismAnticoagulant EffectAspirinPD BarbituratePKCimetidinePK DipyridamolePD FibratesPD FluvoxaminePK Macrolides PKPhenytoinPKQuinolonesPK RifampinPKSulfinpyrazonePK/PD Thyroid hormonesPD Ticlopidine PD N Engl J Med.2003;14;349:675-83;JAPHA 2004;44:142-51,Clinically SignificantDrug-Drug Interactions with AEDs,Object DrugInteracting DrugOutcomeCarbamazepineDanazol CBZ levelCarbamazepineDiltiazem CBZ levelCarbamazepineMacrolides CBZ levelCarbamazepinePropoxyphene CBZ levelCarbamazepineVerapamil CBZ levelPhenytoinAmiodarone DPH levelPhenytoinCimetidine DPH levelPhenytoinFluoxetine DPH levelPhenytoinINH DPH levelPhenytoinOmeprazole DPH levelNeuropharmacology 2002;5:280-9,Inducers of Hepatic Cytochrome P450,1A2 2C9/19 2D6 3A4SmokingRifampinNoneCarbamazepineOmeprazolePhenobarbitalPhenytoinPhenytoinPhenytoinPhenobarbitalRifampinSt.Johns wortwww.drug-,Effect of Age on Theophylline Hepatic Metabolism Induction by DPH,Crowley J.J Phamacol Exp Ther 1988;245:513-23.,Selected Phenytoin Induction Interactions,Object DrugInteracting DrugCYP Isoenzyme InducedMethadone Phenytoin3A4QuinidinePhenytoin3A4TheophyllinePhenytoin1A2WarfarinPhenytoin2C9Neuropharmacology 2002;5:280-9.,Selected Drugs Secreted by Renal Tubules,Basic(cationic)AgentsAmiodaroneCimetidineDigoxinProcainamideQuinidineRanitidineTrimethoprimVerapamil,Acidic(Anionic)AgentsCephalosporinsIndomethacinMethotrexatePenicillinsProbenecidSalicylatesThiazides,Drug-Drug Interactions With Digoxin,Interacting DrugEffect on LevelsAmiodarone Clarithromycin Propafenone Quinidine Verapamil Drug Saf.2000;23:509-32;JAPHA 2004;44:142-51,Drugs that Interact with Lithium,DiureticsACE-INSAIDs,Pharmacokinetics,Pharmacodynamics,DosageRegimen,Effects,PlasmaConcentration,Site ofAction,Drug-Drug PD Interactions,Object DrugInteracting Drug(s)ACE-I K+&K+sparing diureticsBeta blockersVerapamilDigoxinDiureticsMAOI SSRI,Dextromethorphan,Pseudoephedrine,AnorexiantsMeperidineMAOIHydroxyineThioridazine,Drug-TCA PD Interactions,Concurrent use with any other drugs with antimuscarinic propertiesConcurrent MAOIType I antiarrhythmicsClonidineGuanadrelGuanethidine,Drug-NSAID PD Interactions,Object Drug Interacting DrugOutcomeAntihypertensivesNSAIDs BPCorticosteroidsNSAIDs risk of PUD DiureticsNSAIDs diuretic effectTriamtereneIndomethacin K+WarfarinNSAIDs anticoagulant effect,CNS Polypharmacy and Falls in Elderly Persons,Weiner D,et al.Gerontol 1998;44:217-21,Drug-Food/Nutrient Interactions,Clinically Significant Drug St.John Wort Interactions,Object Drug OutcomeAntidepressantsserotonergic syndromeCyclosporine levels,transplant rejectionDigoxin digoxin levelsEstrogen breakthrough bleedingIndinavir indinavir levelsMethadonewithdrawal sxsTacrolimus levelsTheophylline theophylline levelsWarfarin INRCPT 2004;75:1-12,Other Clinically Significant Herb-Drug Interactions,Object DrugInteracting DrugOutcomeAnticonvulsantsWormwood seizure thresholdAnticonvulsantsGingko biloba seizure thresholdDigoxinHawthorne digoxin activitySaquinavirGarlic saquinavir levelsWarfarinFeverfew risk of bleedingWarfarinGarlic risk of bleedingWarfarinGinger risk of bleedingWarfarinGinkgo risk of bleedingWarfarinGinseng anticoagulantLancet 2000;355:134-8.,Clinically Important Drug-Disease Interactions Determined by Expert Panel Consensus,DrugDiseaseAnticholinergicsBPH,constipation,dementiaAntiarrhythmics(Type 1A)CHF(systolic dysfunction)AmphetaminesHTN,insomniaAspirinPUDAtypical antipsychoticsDMBarbituratesDepressionBenzodiazepines COPD,dementia,fallsBeta-blockersCOPD,DM,syncopeCCB 1st generation CHF(systolic dysfunction)ChlorpromazinePostural hypotension,seizuresClozapineSeizuresCorticosteroidsDM,PUDDecongestantsInsomniaDigoxinHeart blockLindblad C,Hanlon J et al.(abstract)J Am Geriatr Soc 2004;52:S135,Clinically Important Drug-Disease Interactions Determined by Expert Panel Consensus,DrugDiseaseMetoclopramideParkinsons diseaseNitrofurantoinChronic renal failureNon-aspirin NSAIDsCRF,CHF,HTNNon-aspirin,non-COX II NSAIDsPUDOpioid analgesicsBPH,constipation,dementiaSedative/hypnoticsFallsSkeletal muscle relaxants BPHSSRIsFallsTheophyllineInsomniaThioridazinePostural hypotension,seizuresThorazineSeizuresTricyclic antidepressants Arrhythmias,BPH,constipationdementia,falls,heart blockpostural hypotensionTypical antipsychotics Falls,Learning Objectives,At the conclusion of this talk the participant should be able to:List the 4 major types of drug interactions that can occur in the elderlyDiscuss the epidemiology of the different types of drug interactions in the elderlyImplement strategies to prevent/manage drug interactions in the elderly,Epidemiology of Drug-Drug or Drug-Disease Interactions,Incidence of potential drug-drug interactions ranges from 2-17%of all Rxs and up to 6-42%of elderly patients.Incidence of potentially clinically significant drug interactions is low in the elderly(usually must involve narrow therapeutic range drug and inhibitor/inducer of drug metabolism or renal excretion)There is evidence suggesting that adverse health outcomes associated with drug-drug interactions is infrequent.Drug-disease interactions occur in 6.2-40%of elderly patientsDrug disease interactions may result in higher risk of adverse outcomes(e.g.,decline in functional status and increased health services use)due to alterations in homeostatic mechanisms and diminished functional reserve.,Drug Interactions Are Avoidable,Gosney et al.Lancet 1984;2:564,Strategies to Prevent/Manage Drug Interactions,1.Encourage patients to report all prescription,over-the-counter and complementary and alternative drugs at every health care encounter.2.Support the implementation of electronic prescribingand/or the use by patients of one pharmacy with updated drug interaction software.3.Work with pharmacists and be familiar with drug interaction information sources 4.Consider whether drug therapy is necessary5.When adding a new drug to regimen,screen for potential drug-drug interactions.,Strategies to Prevent/Manage Drug Interactions,6.When adding a new drug to regimen in a patient,screen for potential drug-disease interaction.7.If drug interaction can not be avoided,adjust doses and or/dosage intervals for affected medication and monitor the patient closely.8.Carefully monitor other drug therapy when withdrawing a drug that can inhibit or induce hepatic metabolism.9.Regularly review the need for chronic medications-reduce polypharmacy,Learning Objectives,At the conclusion of this talk the participant should be able to:List the 4 major types of drug interactions that can occur in the elderlyDiscuss the epidemiology of the different types of drug interactions in the elderlyImplement strategies to prevent/manage drug interactions in the elderly,