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1、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 elderl
2、yImplement 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,IronTetra
3、cycline,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
4、 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,Carbam
5、azepinewww.drug-,Inhibitors of Hepatic Cytochrome P450,1A2 2C9/19 2D6 3A4FluvoxamineAmiodaroneFluoxetineErythromycinCimetidineFluconazoleParoxetineAzole antifungalCiprofloxacinFluvastatinQuinidineNefazodoneFluoxetineRitonavirClarithromycinIsoniazidBupropionRitonavirSertralineCimetidineCimetidineOmep
6、razoleCimetidinewww.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,InducersBarbituratesPhen
7、ytoinSmokingRifampinCarbamazepineJAPHA 2004;44:142-51,Drug-Drug Interactions With Warfarin,Interacting DrugMechanismAnticoagulant EffectAspirinPD BarbituratePKCimetidinePK DipyridamolePD FibratesPD FluvoxaminePK Macrolides PKPhenytoinPKQuinolonesPK RifampinPKSulfinpyrazonePK/PD Thyroid hormonesPD Ti
8、clopidine 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 levelCarbamazepineVe
9、rapamil 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 3A4SmokingRifampinNoneCarbamazepineOmeprazolePhenobarbitalPheny
10、toinPhenytoinPhenytoinPhenobarbitalRifampinSt.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 Phenytoin3A4Quinidine
11、Phenytoin3A4TheophyllinePhenytoin1A2WarfarinPhenytoin2C9Neuropharmacology 2002;5:280-9.,Selected Drugs Secreted by Renal Tubules,Basic(cationic)AgentsAmiodaroneCimetidineDigoxinProcainamideQuinidineRanitidineTrimethoprimVerapamil,Acidic(Anionic)AgentsCephalosporinsIndomethacinMethotrexatePenicillins
12、ProbenecidSalicylatesThiazides,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,DosageRegi
13、men,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 w
14、ith 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+War
15、farinNSAIDs 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 rejectionD
16、igoxin 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 thre
17、sholdAnticonvulsantsGingko biloba seizure thresholdDigoxinHawthorne digoxin activitySaquinavirGarlic saquinavir levelsWarfarinFeverfew risk of bleedingWarfarinGarlic risk of bleedingWarfarinGinger risk of bleedingWarfarinGinkgo risk of bleedingWarfarinGinseng anticoagulantLancet 2000;355:134-8.,Clin
18、ically Important Drug-Disease Interactions Determined by Expert Panel Consensus,DrugDiseaseAnticholinergicsBPH,constipation,dementiaAntiarrhythmics(Type 1A)CHF(systolic dysfunction)AmphetaminesHTN,insomniaAspirinPUDAtypical antipsychoticsDMBarbituratesDepressionBenzodiazepines COPD,dementia,fallsBet
19、a-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 Interaction
20、s Determined by Expert Panel Consensus,DrugDiseaseMetoclopramideParkinsons diseaseNitrofurantoinChronic renal failureNon-aspirin NSAIDsCRF,CHF,HTNNon-aspirin,non-COX II NSAIDsPUDOpioid analgesicsBPH,constipation,dementiaSedative/hypnoticsFallsSkeletal muscle relaxants BPHSSRIsFallsTheophyllineInsomn
21、iaThioridazinePostural 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
22、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 interactio
23、ns 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 a
24、dverse 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 h
25、omeostatic 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 encount
26、er.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
27、,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 monito
28、r 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,
