Drug Interactions in Older Adults[老年人药物相互作用](PPT33)

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 elderly discuss the epidemiology of the different types of drug interactions in the e

2、lderly implement strategies to prevent/manage drug interactions in the elderly types of drug interactions 1.drug-drug pharmacokinetic 2.drug-drug pharmacodynamic 3.drug-food/nutrient 4.drug-disease drug-drug interactions affecting absorption and distribution precipitant drug(s)object drug(s) outcome

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

4、i conjugation glucuronidation sulfation glycine acetylation cytochrome p450 phase i isoenzymes, % total and substrate examples isoenzymes % substrate cyp1a217olanzapine, theophylline cyp2c9/1926phenytoin, warfarin cyp2d62-4codeine, desipramine, tramadol cyp2e19-10chlorzoxazone, ethanol cyp3a435-45 d

5、iazepam, triazolam, quinidine, methadone, carbamazepine www.drug- inhibitors of hepatic cytochrome p450 1a2 2c9/19 2d6 3a4 fluvoxamine amiodaronefluoxetineerythromycin cimetidinefluconazoleparoxetineazole antifungal ciprofloxacin fluvastatinquinidinenefazodone fluoxetineritonavirclarithromycin isoni

6、azidbupropionritonavir sertralinecimetidinecimetidine omeprazole cimetidine www.drug- j pharmacol exp ther 1997;280:627-37. effect of age on theophylline hepatic metabolism inhibition drugs that interact with theophylline inhibitors cimetidine propafenone mexiletine propranolol erythromycin ciproflo

7、xacin fluvoxamine drugs aging. 2003;20:71-84 inducers barbiturates phenytoin smoking rifampin carbamazepine japha 2004;44:142-51 drug-drug interactions with warfarin interacting drugmechanismanticoagulant effect aspirinpd barbituratepk cimetidinepk dipyridamolepd fibratespd fluvoxaminepk macrolides

8、pk phenytoinpk quinolonespk rifampinpk sulfinpyrazonepk/pd thyroid hormonespd ticlopidine pd n engl j med. 2003; 14;349:675-83; japha 2004;44:142-51 clinically significant drug-drug interactions with aeds object druginteracting drugoutcome carbamazepinedanazol cbz level carbamazepinediltiazem cbz le

9、vel carbamazepinemacrolides cbz level carbamazepinepropoxyphene cbz level carbamazepineverapamil cbz level phenytoinamiodarone dph level phenytoincimetidine dph level phenytoinfluoxetine dph level phenytoininh dph level phenytoinomeprazole dph level neuropharmacology 2002;5:280-9 inducers of hepatic

10、 cytochrome p450 1a2 2c9/19 2d6 3a4 smokingrifampinnonecarbamazepine omeprazolephenobarbitalphenytoin phenytoinphenytoinphenobarbital rifampin st. johns wort www.drug- effect of age on theophylline hepatic metabolism induction by dph crowley j. j phamacol exp ther 1988;245:513-23. selected phenytoin

11、 induction interactions object druginteracting drugcyp isoenzyme induced methadone phenytoin3a4 quinidinephenytoin3a4 theophyllinephenytoin1a2 warfarinphenytoin2c9 neuropharmacology 2002;5:280-9. selected drugs secreted by renal tubules basic (cationic) agents amiodarone cimetidine digoxin procainam

12、ide quinidine ranitidine trimethoprim verapamil acidic (anionic) agents cephalosporins indomethacin methotrexate penicillins probenecid salicylates thiazides drug-drug interactions with digoxin interacting drugeffect on levels amiodarone clarithromycin propafenone quinidine verapamil drug saf. 2000;

13、23:509-32; japha 2004;44:142-51 drugs that interact with lithium diuretics ace-i nsaids pharmacokineticspharmacodynamics dosage regimen effects plasma concen tration site of action drug-drug pd interactions object druginteracting drug (s) ace-i k+ 44:217-21 drug-food/nutrient interactions drugeffect

14、 phenytoin folate isoniazid vit b6 phenytoin absorption with ng feedings levodopahigh protein meals effect blood- brain transport captoprilaltered taste sensation clinically significant drug st. john wort interactions object drug outcome antidepressantsserotonergic syndrome cyclosporine levels, tran

15、splant rejection digoxin digoxin levels estrogen breakthrough bleeding indinavir indinavir levels methadonewithdrawal sxs tacrolimus levels theophylline theophylline levels warfarin inr cpt 2004;75:1-12 other clinically significant herb- drug interactions object druginteracting drugoutcome anticonvu

16、lsantswormwood seizure threshold anticonvulsantsgingko biloba seizure threshold digoxinhawthorne digoxin activity saquinavirgarlic saquinavir levels warfarinfeverfew risk of bleeding warfaringarlic risk of bleeding warfaringinger risk of bleeding warfaringinkgo risk of bleeding warfaringinseng antic

17、oagulant lancet 2000;355:134-8. clinically important drug-disease interactions determined by expert panel consensus drugdisease anticholinergicsbph, constipation, dementia antiarrhythmics (type 1a) chf (systolic dysfunction) amphetamineshtn, insomnia aspirinpud atypical antipsychoticsdm barbiturates

18、depression benzodiazepines copd,dementia, falls beta-blockerscopd, dm, syncope ccb 1st generation chf (systolic dysfunction) chlorpromazinepostural hypotension, seizures clozapineseizures corticosteroidsdm, pud decongestantsinsomnia digoxinheart block lindblad c, hanlon j et al. (abstract) j am geri

19、atr soc 2004;52:s135 clinically important drug-disease interactions determined by expert panel consensus drugdisease metoclopramideparkinsons disease nitrofurantoinchronic renal failure non-aspirin nsaidscrf, chf, htn non-aspirin, non-cox ii nsaidspud opioid analgesicsbph, constipation, dementia sed

20、ative/hypnoticsfalls skeletal muscle relaxants bph ssrisfalls theophyllineinsomnia thioridazinepostural hypotension, seizures thorazineseizures tricyclic antidepressants arrhythmias, bph, constipation dementia, falls, heart block postural hypotension typical antipsychotics falls learning objectives

21、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 elderly discuss the epidemiology of the different types of drug interactions in the elderly implement strategies to prevent/manage drug interactions in the elderly epid

22、emiology 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 d

23、rug 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 patients drug disease interactions may result in higher risk of adver

24、se 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 previous adverse reactions contraindicated drugs drug interactions totals

25、 avoidable75767131 probably avoidable -3737 uncertain-32932 total760133200 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 prescribing and/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 necessary 5. whe