DrugInteractionsinOlderAdults老年人藥物相互作用PPT33

1、drug interactions in older adultsjoseph t. hanlon, pharmd, mslearning objectivesat the conclusion of this talk the participant should be able to: list the 4 major types of drug interactions that can occur in the elderly discuss the epidemiology of the different types of drug interactions in the elde

2、rly implement strategies to prevent/manage drug interactions in the elderlytypes of drug interactions1.drug-drug pharmacokinetic2.drug-drug pharmacodynamic3.drug-food/nutrient4.drug-diseasedrug-drug interactions affecting absorption and distributionprecipitant drug(s)object drug(s) outcomeantacids,

3、irontetracycline, ciprofloxacin abs.chloral hydratewarfarin ppbgenerally absorption and distribution drug-drug-interactions are not clinically important.drugs & aging 1998;12:485-94hepatic metabolism phase i (cyp 450) oxidation hydroxylation dealkylation sulfoxidation reduction hydrolysis phase

4、ii conjugation glucuronidation sulfation glycine acetylationcytochrome p450 phase i isoenzymes, % total and substrate examples isoenzymes % substratecyp1a217olanzapine, theophyllinecyp2c9/1926phenytoin, warfarincyp2d62-4codeine, desipramine, tramadolcyp2e19-10chlorzoxazone, ethanolcyp3a435-45 diazep

5、am, triazolam, quinidine,methadone, carbamazepinewww.drug-inhibitors of hepatic cytochrome p450 1a2 2c9/19 2d6 3a4fluvoxamine amiodaronefluoxetineerythromycincimetidinefluconazoleparoxetineazole antifungalciprofloxacin fluvastatinquinidinenefazodonefluoxetineritonavirclarithromycinisoniazidbupropion

6、ritonavirsertralinecimetidinecimetidineomeprazolecimetidinewww.drug-j pharmacol exp ther 1997;280:627-37.effect of age on theophylline hepatic metabolism inhibitiondrugs that interact with theophyllineinhibitors cimetidine propafenone mexiletine propranolol erythromycin ciprofloxacin fluvoxaminedrug

7、s aging. 2003;20:71-84inducers barbiturates phenytoin smoking rifampin carbamazepinejapha 2004;44:142-51drug-drug interactions with warfarininteracting drugmechanismanticoagulant effectaspirinpd barbituratepkcimetidinepk dipyridamolepd fibratespd fluvoxaminepk macrolides pkphenytoinpkquinolonespk ri

8、fampinpksulfinpyrazonepk/pd thyroid hormonespd ticlopidine pd n engl j med. 2003; 14;349:675-83; japha 2004;44:142-51clinically significantdrug-drug interactions with aedsobject druginteracting drugoutcomecarbamazepinedanazol cbz levelcarbamazepinediltiazem cbz levelcarbamazepinemacrolides cbz level

9、carbamazepinepropoxyphene cbz levelcarbamazepineverapamil cbz levelphenytoinamiodarone dph levelphenytoincimetidine dph levelphenytoinfluoxetine dph levelphenytoininh dph levelphenytoinomeprazole dph levelneuropharmacology 2002;5:280-9inducers of hepatic cytochrome p450 1a2 2c9/19 2d6 3a4smokingrifa

10、mpinnonecarbamazepineomeprazolephenobarbitalphenytoinphenytoinphenytoinphenobarbitalrifampinst. 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 interactionsobject druginteracting drugcyp

11、isoenzyme inducedmethadone phenytoin3a4quinidinephenytoin3a4theophyllinephenytoin1a2warfarinphenytoin2c9neuropharmacology 2002;5:280-9. selected drugs secreted by renal tubulesbasic (cationic) agents amiodarone cimetidine digoxin procainamide quinidine ranitidine trimethoprim verapamilacidic (anioni

12、c) agents cephalosporins indomethacin methotrexate penicillins probenecid salicylates thiazidesdrug-drug interactions with digoxininteracting drugeffect on levelsamiodarone clarithromycin propafenone quinidine verapamil drug saf. 2000;23:509-32; japha 2004;44:142-51drugs that interact with lithium d

13、iuretics ace-i nsaidspharmacokineticspharmacodynamicsdosageregimeneffectsplasmaconcentrationsite ofactiondrug-drug pd interactionsobject druginteracting drug (s)ace-i k+ & k+ sparing diureticsbeta blockersverapamildigoxindiureticsmaoi ssri, dextromethorphan, pseudoephedrine, anorexiantsmeperidin

14、emaoihydroxyinethioridazinedrug- tca pd interactions concurrent use with any other drugs with antimuscarinic properties concurrent maoi type i antiarrhythmics clonidine guanadrel guanethidinedrug-nsaid pd interactionsobject drug interacting drugoutcomeantihypertensivesnsaids bpcorticosteroidsnsaids

15、risk of pud diureticsnsaids diuretic effecttriamtereneindomethacin k+warfarinnsaids anticoagulant effectcns polypharmacy and falls in elderly personsweiner d, et al. gerontol 1998;44:217-21drug-food/nutrient interactionsdrugeffectphenytoin folateisoniazid vit b6phenytoin absorption with ng feedingsl

16、evodopahigh protein meals effect blood-brain transportcaptoprilaltered taste sensationclinically significant drug st. john wort interactionsobject drug outcomeantidepressantsserotonergic syndromecyclosporine levels, transplant rejectiondigoxin digoxin levelsestrogen breakthrough bleedingindinavir in

17、dinavir levelsmethadonewithdrawal sxstacrolimus levelstheophylline theophylline levelswarfarin inrcpt 2004;75:1-12other clinically significant herb- drug interactions object druginteracting drugoutcomeanticonvulsantswormwood seizure thresholdanticonvulsantsgingko biloba seizure thresholddigoxinhawth

18、orne 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

19、 panel consensusdrugdisease anticholinergicsbph, constipation, dementia antiarrhythmics (type 1a) chf (systolic dysfunction) amphetamineshtn, insomnia aspirinpud atypical antipsychoticsdm barbituratesdepression benzodiazepines copd,dementia, falls beta-blockerscopd, dm, syncope ccb 1st generation ch

20、f (systolic dysfunction) chlorpromazinepostural hypotension, seizures clozapineseizures corticosteroidsdm, pud decongestantsinsomnia digoxinheart blocklindblad c, hanlon j et al. (abstract) j am geriatr soc 2004;52:s135clinically important drug-disease interactions determined by expert panel consens

21、usdrugdisease metoclopramideparkinsons disease nitrofurantoinchronic renal failure non-aspirin nsaidscrf, chf, htn non-aspirin, non-cox ii nsaidspud opioid analgesicsbph, constipation, dementia sedative/hypnoticsfalls skeletal muscle relaxants bph ssrisfalls theophyllineinsomnia thioridazinepostural

22、 hypotension, seizures thorazineseizures tricyclic antidepressants arrhythmias, bph, constipationdementia, falls, heart blockpostural hypotension typical antipsychotics falls learning objectivesat the conclusion of this talk the participant should be able to: list the 4 major types of drug interacti

23、ons that can occur in the elderly discuss the epidemiology of the different types of drug interactions in the elderly implement strategies to prevent/manage drug interactions in the elderlyepidemiology of drug-drug or drug-disease interactionsincidence of potential drug-drug interactions ranges from

24、 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 heal

25、th 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 homeost

26、atic mechanisms and diminished functional reserve.drug interactions are avoidablegosney et al. lancet 1984;2:564previous adverse reactionscontraindicated drugsdrug interactionstotalsavoidable75767131probably avoidable-3737uncertain-32932total760133200strategies to prevent/manage drug interactions1.

27、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 source