1. GERIATRIC PHARMACOLOGY Prof. M. Kršiak Department of Pharmacology, Third Faculty of Medicine, Charles University in Prague Cycle II, Modul NURG ( nephrology, urology, rheumatology a geriatry– CVSE4P0023 Charles University in Prague, Third Faculty of Medicine Academic year 2012-2013 GENERAL MEDICINE 6-YEAR MASTER‘S STUDY PROGRAMME http://vyuka.lf3.cuni.cz CVSE4P0023 TU 531

2. 1. Drugs can significantly increase life excpectancy and quality of life in old age 2. However, they can also produce the opposite OLD AGE MAY HAVE A HIGH VALUE How to realize the first possibility and avoid the second one?

3. 1.Factors affecting drug effects in older adults 2.Inappropriate pharmacotherapy in the elderly („Beers criteria“) 3.Analgesics in older adults „older adults“ or the ‚elderly‘ = > 65 yers old age of 65 years is accepted as a definition of 'elderly' or older person

4. 1.Pharmacokinetic changes 2.Pharmacodynamic changes 3. Less robust homeostasis 4. Concomitant diseases 5. Polypharmacy (↑drug interactions) Factors influencing drug effects in older adults (>65y):

5. - reduced elimination (major factor) kidney  aminoglycosides, digoxin [Case study 1], atenolol, ranitidin liver  diazepam  halflife („tolik hodin, kolik je let“) - distribution (  water/  fat, minor factor) - absorption (minor factor) 1. Pharmacokinetic changes: Factors influencing drug effects in older adults (>65y):

6. Case Study No. 1 1. An 85-year-old man complaining of chest pain and shortness of breath was brought to the emergency room 2. ECG revealed atrial fibrilation. The patient was given a standard dose of digoxin (a loading dose 1 mg over the 24 hours followed by a maintenance oral dose of 0.25 mg/day) By the third day the patient was ambulating comfortably, with normal sinus rhytm. He was discharged. Melmon-Morrelli‘s Clinical Pharmacology 2000, p.1165 Do you agree with this dosage? YES / NO / DON‘T KNOW

7. Case Study No. 1 - contd: 3. Six days later, the man was brought back to the hospital. There he complained of nausea and vomiting. He was disoriented. The serum digoxin concentration was 2.7 ng/ml Melmon-Morrelli‘s Clinical Pharmacology 2000, str.1165 SPC and Beers criteria: do not give more than 0.125 mg/day in the old age (>65 years of age)

8. 2. Pharmacodynamic changes – due to ageing e.g. in targets for drug actions consequences e.g. confusion, cognitive impairment, delirium Factors influencing drug effects in older adults (>65y):

9. CONFUSION can be caused by various drugs in the old age, particularly by: benzodiazepines, drugs with anticholinergic effects (e.g. some antidepressants, antipsychotics), opioids, levodopa, but also by: metoprolol (or other betablockers), ranitidin (or other H2 antagíonists), corticoids, digoxin, lithium, anticonvulsants, and others

10. 3. Less robust homeostasis e.g. antihypertensives –orthostatic hypotension more likely and other changes in the old age e.g. prostatic hypertrophy – anticholinergic drugs - micturition problems (urinary retention or too frequent needs to urinate during night, etc) Factors influencing drug effects in older adults (>65y):

11. 4. Concomitant diseases e.g. - NSAIDs 10x  risk of hospitalization due to cardiac insufficiency in patients with preceding/concomitant cardiac disorders - cardiac insufficiency  lower blood flow in the liver   lower 1st-pass effect   halflife of morphine Factors influencing drug effects in older adults (>65y):

12. 5. Polypharmacy (↑drug interactions) e.g. SSRI + NSAIDs 13x  risk of GIT bleeding SSRI + warfarin  risk of bleeding Factors influencing drug effects in older adults (>65y):

13. How to improve pharmacotherapy in older adults? 1. Withdraw unnecessary drugs or reduce doses if appropriate 2. Determine whether „manifestations of the old age“ such as confusion, urination problems, dizzines, insomnia, etc are not due to drugs 3. In general, begin therapy with low doses 4. If possible avoid administration of drugs inappropriate (more risky) in the old age („Beers criteria“). Instead select more appropriate alternative drugs. 5. Simplify use of drugs and encourage of compliance - try to avoid intermittent schedules; once daily dosage is ideal - give clear instructions, best in a written form

14. “Manifestations of the old age” that might be caused (or increased) by drugs desorientation, confusion [e.g. benzodiazepines and many other drugs (see above)], dizziness [many drugs, e.g. tramadol] orthostatic hypotension [antihypertensives, antipsychotics] hypertension [OTC medicines reducing nasal congestion – [Case Study No.2] extrapyramidal symptoms [metoclopramide] problems with prostatic hypertrophy [ Case Study No. 3]

15. Case Study No. 2 („manifestations of the old age“ induced/increased by drugs) 1. A 79-year-old woman with hypertension well controlled with thiazides (140/70) 2. At a new visit, her blood pressure was found to be 170/90. This was recorded on two other occasions during the following week 3. She had recently been complaining of nasal congestion. So she had bought an OTC preparation for relief of these symptoms. 4. The preparation contained phenylpropanolamine. This medication was discontinued with return to normotensive readings. Melmon-Morrelli‘s Clinical Pharmacology 2000, str.1166

16. Case Study No. 3 („manifestations of the old age“ induced or increased by drugs) 1. A 72-year-old man visited his physician with concerns about difficulty sleeping 2. The physician prescribed diphenhydramine 3. The patient‘s sleep was better, but he had to arise several times a night to urinate. He was referred to a urologist. 4. The urologist revealed a benign prostatic hypertorophy with post void residual. The patient was scheduled for the prostatectomy. Melmon-Morrelli‘s Clinical Pharmacology 2000, str.1172

17. Inappropriate pharmacotherapy in the elderly („Beers criteria“)

18. Beers criteria:Potentially Inappropriate Medication Use in Older Adults - Beers List Fick D.M. et al.: Archives of Internal Medicine 163: 2716-2724, 2003* examples: Benzodiazepines Drugs with anticholinergic effects Nonsteroid Antiinflammatory Drugs (NSAIDs) Some cardiovascular drugs methyldopa, amiodaron, digoxin > 0,125 mg/d, Some opioids pethidin, pentazocin Miscellanea cimetidine, androgens, estrogens *Several upgrades of the list have been published since that time in several countries. Recently by Topinková et al. Praktický lékař 92 (1): 11-22, 2012 indicating also alternative more appropriate drugs.

19. Beers criteria:Potentially Inappropriate Medication Use in Older Adults Medications to be avoided in older adults with these conditions Fick D.M. et al.: Archives of Internal Medicine 163: 2716-2724, 2003 examples: Urination problems Drugs with anticholinergic effects Hypertension Sympatomimetics Arrhytmia Tricykcic antidepressants Parkinson‘s disease Metoclopramide, 1st generation antipsychotics Constipation Drugs with anticholinergic effects Calcium channel blockers ObesityOlanzapin Insomnia Sympatomimetics Cognition disorders Drugs with anticholinergic effects Benzodiazepines

20. ANALGESICS IN OLDER ADULTS

22. J M Seager, C J Hawkey, BMJ, 2001;323:1236-1239 Hospitalisations for severe GI adverse reactions caused by NSAIDs

23. without NSAIDs: 2-3 GI bleeding / 1000 pacients >65y/year, ca 5 GI bleeding / 1000 pacients >85y/year

24. NSAIDs moderately increase a risk of myocardial infarction : risk of myocardial infarction: rofecoxib 1.32 (1.09-1.61) ibuprofen 1.24 (1.11-1.39) diclofenac 1.55 (1.39-1.72) Hippisley-Cox, Coupland BMJ 11 June 2005 Vol.330;pp1366-

25. paracetamol opioids Analgesics more appropriate in older adults (then nsaidS): both belong among safest analgesics (at therapeutic doses and non-invasive administration [ dipyrone?, propyfenazone?]

26. Most frequently used analgesics in the elderly: ČR* USA ** ibuprofen38,7 %6,2% diclofenac 19,4 %2,3% thiaprofenic acid 13,7 %- tramadol 8,1 %5,7% indometacin 4,0 %0,4% Alnagon 3,2 % - propoxyfen - 18,1% paracetamol 2,4 %37,4% *541 persons > 75 y **18 394 pers. > 65y Kubešová et al. 2001 Won et al. 2003

27. SUMMARY I: 1.In older patients we shoud take into account: lower elimination of drugs, higher probability of some adverse effects, concomitant diseases, polypharmacy 2.In older patients we shoud apply „Beers criteria“, i.e. we should try to avoid inapproriate drugs and select more appropriate alternatives if possible

28. 3. In older patients there are more appropriate analgesics containing paracetamol alone or in combination with opioids (than NSAIDs) 4. If NSAIDs are necessary, it is advisable to administer them with proton pump inhibitors or, if possible, locally SUMMARY II: