1. POLYPHARMACY in elderly D TRAN M.D.

2. OBJECTIVES Introduce statistical data & Physiological changes Population at risk, cause of Polypharmacy, inducers/inhibitors CYP450, BEERS CRITERIA & side effects of polypharmacy Discuss on preventions

3. STATISTICAL DATA

6. Most frequently used by Medicare patients: Cardiovascular agents Abx Diuretics Opioids Antihyperlipidemics

7. Most common non-prescription medications: – Pain – cold & cough – Vitamins or nutrient

8. PHYSIOLOGICAL CHANGES of aging

12. Population at risk

13. Multiple co- morbidities – Poor health – Depression – HTN – Anemia – Asthma – Angina – Diverticulosis – OA – Gout – DM

14. Population at risk Access to care – # of visits – Supplemental insurance – Multiple providers Demographic – Increased age – White – education

15. Who causes poly- pharmacy ?

17. POLYPHARMACY Most likely causes: unnecessary prescribing uncertain diagnosis insufficient education redundant/misleading promotion Various pharmacies

18. THE EFFECT OF MEDICATIONS IN OUR BODIES

19. POLYPHARMACY Drug combinations: Synergistic significant toxicity Drug-Disease interaction: dementia, CKD Drug-Nutrient: Grapefruit juice (inhibitor) Drug-Drug interaction: inducers/inhibitors CYP450

20. INDUCERS CYP P450 AMOBARBITAL ARMODAFINIL Bosentan Carbamazepine Dexamethasone EFAVIRENZ Fosphenytoin Nafcillin nevirapine Oxcarbazepine PENTOBARBITAL PHENOBARBITAL Phenytoin Primidone Rifabutin Rifampin Rifapentine SECOBARBITAL

21. INHIBITORS CYP P450 AMIODARONE Amlodipine Aprepitant ARMODAFINIL Atazanavir Bortezomib Caffeine Celecoxib Chloroquine CHLORPROMAZINE Cimetidine Cinacalcet Ciprofloxacin Clarithromycin CLOMIPRAMINE Clotrimazole CLOZAPINE Cocaine conivaptan

22. INHIBITORS CYP P450 Cyclosporine Darifenacin Delavirdine Desipramine Dexlansoprazole Dexmedetomidine DICLOFENAC Diltiazem DIPHENHYDRAMINE Disulfiram Doxorubicin Doxycycline Duloxetine EFAVIRENZ Esomeprazole Felodipine Fluconazole fluoxetine

23. INHIBITORS CYP P450 Flurbiprofen Fluvastatin Fluvoxamine Fosamprenavir Fosaprepitant Fospropofol Gemfibrozil HALOPERIDOL IBUPROFEN Imatinib IMIPRAMINE Indinavir INDOMETHACIN Irbesartan Isoniazid Ketoconazole Lansoprazole Letrozole

24. INHIBITORS CYP P450 Lidocaine Loratadine Losartan MEFENAMIC ACID Methadone Methoxsalen Metronidazole Mexiletine Miconazole modafinil Nefazodone Nelfinavir Nicardipine NIFEDIPINE Norfloxacin Ofloxacin Omeprazole Paroxetine Pioglitazone PIROXICAM

25. INHIBITORS CYP P450 Posaconazole Primaquine Propofol Pyrimethamine QUINIDINE Quinine Rabeprazole Ranolazine Ritonavir rosiglitazone Saquinavir Sertraline Sitaxsentan Sorafenib Sulfadiazine Sulfamethoxazole Tamoxifen Telithromycin Terbinafine tetracycline

26. INHIBITORS CYP P450 Thiabendazole THIORIDAZINE Thiotepa TICLOPIDINE Tolbutamide Tranylcypromine Trimethoprim Verapamil voriconazole Warfarin Zafirlukast zileuton

27. BEERS CRITERIA ANTICHOLINERGICS (excludes TCAs) First generation antihistamines (single or combination) – Brompheniramine – Carbinoxamine – Chlorpheniramine – Clemastine – Cyproheptadine – Dexbrompheniramine – Dexchlorpheniramine – DIPHENHYDRAMINE (oral) – Doxylamine – Hydroxyzine – Promethazine – triprolidine

28. BEERS CRITERIA ANTIPARKINSON – Benztropine (oral) – trihexyphenidyl ANTISPASMODICS – Belladonna alkaloids – Clidinium- chlordiazepoxide – Dicyclomine – Hyoscyamine – Propantheline – Scopolamine ANTITHROMBOTICS – Dipyridamole, oral short acting – ticlopidine ANTI-INFECTIVE – nitrofurantoin CARDIOVASCULAR – Alpha1 blockers: Doxazosin Prazosin Terazosin

29. BEERS CRITERIA CARDIOVASCULAR – Alpha agonists, central Clonidine Guanabenz Guanfacine Methyldopa Reserpine (>0.1mg/d) – Antiarrhythmic drugs (class Ia, Ic, III) Amiodarone Dofetilide Dronedarone Flecainide Ibutilide Procainamide Propafenone Quinidine sotalol

30. BEERS CRITERIA CARDIOVASCULAR – Disopyramide – dronedarone – Digoxin (>0.125mg/d) – Nifedipine IR – Spironolactone (>25mg/d) CNS – 3* TCA (alone or combination) Amitriptyline Chlordiazepoxide- amitriptyline Clomipramine Doxepin >6mg/d Imipramine Perphenazine- amitriptyline trimipramine

31. BEERS CRITERIA CNS – Antipsychotics: 1 st : – Chlorpromazine – Fluphenazine – HALOPERIDOL – Loxapine – Molindone – Perphenazine – Pimozide – Promazine – THIORIDAZINE – Thiothixene – Trifluoperazine – triflupromazine – Antipsychotics: 1 st, 2 nd generation 2 nd : – Aripiprazole – Asenapine – CLOZAPINE – Iloperidone – Lurasidone – Olanzapine – Paliperidone – Quetiapine – Risperidone – ziprasidone

32. BEERS CRITERIA CNS – Thioridazine – Mesoridazine – Barbiturates: Amobarbital Butabarbital Butalbital Mephobarbital Pentobarbital Phenobarbital Secobarbital

33. BEERS CRITERIA – Benzodiazepine Short & intermediate: – Alprazolam – Estazolam – Lorazepam – Oxazepam – Temazepam Long acting: – Clorazepate – Chlordiazepoxide – Chlordiazepoxide- amitriptyline – Clidinium-chlordiazepoxide – Clonazepam – Diazepam – Flurazepam – quazepam – Chloral hydrate – Meprobamate – Nonbenzodiazepine hypnotics Eszopiclone Zolpidem zaleplon – Ergot mesylates – isoxsuprine

34. BEERS CRITERIA ENDOCRINE – Androgens Methyltestosterone testosterone – Desiccated thyroid – Estrogens w/ or w/o progestins – Growth hormone – Insulin, sliding scale – Megestrol – Sulfonylureas, long duration Chlorpropamide glyburide GASTROINTESTINAL – Metoclopramide – mineral oil, oral – Trimethobenzamide

35. BEERS CRITERIA PAIN – Meperidine – Non-COX-selective NSAIDS, oral Aspirin >325mg/d Diclofenac Diflunisal Etodolac Fenoprofen IBUPROFEN ketoprofen Meclofenamate Mefenamic acid Meloxicam Nabumetone Naproxen Oxaprozin Piroxicam Sulindac tolmetin

36. BEERS CRITERIA PAIN – INDOMETHACIN – Ketorolac, includes parenteral – Pentazocine PAIN – Skeletal muscle relaxants Carisoprodol Chlorzoxazone Cyclobenzaprine Metaxalone Methocarbamol orphenadrine

37. SIDE EFFECTS of poly-pharmacy

39. COMMON SIDE EFFECTS FALLS/near falls CONFUSION/dizziness SEDATION COST CONSTIPATION URINARY RETENTION DECREASED PO INTAKE NON-ADHERENCE

41. Preventions

42. PREVENTION TIPS Medication reconciliation at EVERY visit Brown bag method Simple education & verification of understanding

43. PREVENTION TIPS Lower starting dose Generic choices Compliance aids: pillboxes, medication calendars Avoid abbreviated drug names

44. PREVENTION TIPS Review each prescription with patient: name, indication, directions Extra precautions high alert drugs (i.e. anticoagulants, chemotherapy, insulins, opiates, sedatives)

45. SUMMARY Statistical data: live longer, more co-morbidities Physiological changes: decreased lean body mass, increased body fat, decreased volume/working capacity of liver & kidney, age inverse relationship with function Population at risk: multiple co-morbidities, depression, aging Cause: prescribers Inducers/inhibitors/BEERS CRITERIA, side effects: falls or near falls, non-adherence, confusion or dizziness, constipation, urinary retention Preventions: med reconciliation, brown bag method, lower starting dose, generic, compliance aids

46. THANK YOU

47. BIBLIOGRAPHY Semla T.D., Beizer J.L., Higbee M.D. (2013). Geriatric Dosage Handbook: including Cinical Recommendations and Monitoring Guidelines. Hudson: Lexicomp Cruz-Jentoft, A.J., et al., Age and Ageing, 2010. 39(4): p. 412-23.

48. BIBLIOGRAPHY Bilyeu KM, Gumm CJ, Fitzgerald JM, Fox SW, Selig PM. Reducing the use of potentially inappropriate medications in older adults. AJN. Volume 111, No. 1, January 2011; 47-52. Hajjar et al. Poly-pharmacy in elderly patients. The American Journal of Geriatric Pharmacology. Volume 5, No. 4, December 2007; 345-351. Boparai MK, Korc-Grodzicki B. Prescribing for older adults. Mount Sinai Journal of Medicine. 2011; 78:613-626 Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. The New England Journal of Medicine. 2011; 365:2002-2012.

49. BIBLIOGRAPHY Tulner L, Frankfort S, Wesselius F, Van Campen J, Kos C, Beijnen J. Do geriatric outpatients adhere to medication changes advised after assessment? An exploratory pilot study. Current Clinical Pharmacology. 2009, 4, 154-158. Johnson G, Rohan E, Derek S. A systematic review of interventions to improve medication taking in elderly patients prescribed multiple medications. Drugs Aging 2008; 25 (4): 307-324. Milton J, Hill-Smith I, Jackson S. Prescribing for older people. BMJ 2008; 336:606-609. Laufs U, Rettig-Ewen V, Bӧhm M. Strategies to improve drug adherence. European Heart Journal (2011) 32, 264-268.