D partement de M decine CHU Sart Tilman, Li ge

2. Pharmacothérapie et “Patient gériatrique” ?

3. PHARMACOTHERAPY IN THE ELDERLY Modern medications have contributed significantly to increased longevity, improved health and enhanced quality of life for the elderly When not used appropriately, effectively, safely, and correctly, medications may have devastating effects

5. Rx Use and Seniors 1997 - 2.5 billion Rxs

6. Elderly and polypharmacy Seniors accounts for 25% prescriptions Medication use increase with age, and females use more 2/3 elderly take 5-12 meds/day Institutionalized elders average 8-10 medications in a day Over 75 year old take on average nearly 3 prescribed medications and 1.5 across the counter meds daily! Only 15% of community elderly take no prescribed medications In surveys of community elderly serious comprehension problems in 12-16%

7. Consommation médicamenteuse de résidents en maison de repos (n=198)

8. Chronic diseases more prevalent in elderly and polypharmacy may be necessary and appropriate All medication have potential side effects Potential for adverse drug reactions (Larsen and Martin, 1999) -6% when elders take 2 meds -50% when elders take 5 different meds -100% when they take 8 or more meds

9. Elderly susceptible to Adverse Drug Reaction - Polypharmacy - Noncompliance - Altered pharmacokinetics - Multiple chronic disease and conditions - Inappropriate dosing (under/over dosing) - Multiple physicians managing medication

10. "Any symptom in an elderly patient should be considered a drug side effect until otherwise." J Gurwitz, M Monane, S Monane, J Avorn  Brown University Long-term Care Quality Letter 1995

11. Headline - NY TimesJune 3, 1999 (part I) June 4, 1999 (part II) “Death By Prescription The Boom in Medications Brings Rise in Fatal Risks”

12. ADEs and Seniors Incidence in high risk seniors (=>5 Rxs) 35% experienced ADE 95% of ADEs were predictable 63% required MD intervention 10% required ER visit 11% required hospitalization

13. Medication Related Problem Costs $76.6 billion - ambulatory care1 $20.0 billion - acute care2 $4.0 billion - nursing home care3 $100.6 billion direct medical costs of MRPs For seniors : $60 billion (estimated )

14. Adverse Drug Reaction : Conclusions Economic impact for people over age 65 as high as $60 billion annually Suggested contribute to at least 10-15% hospital admissions Medication related problems may be the 3rd or 4th leading cause of death in the over 65 age group Associated with 32,000 hip fx, 163,000 mental impairment and 61,000 cases of drug-induced Parkinson`s disease annually

15. AHRQ Report, 2001

16. Pharmacotherapy in the elderlyTHE BASIC PROBLEM Drug treatment increases (almost exponentially) with age Drug treatment is more risky in the elderly (loss of homeostatic reserve and comorbidities/psychosocial) The elderly are presumed to be - because of pharmacodynamic and pharmacokinetic changes with age - more vulnerable to side effects and toxicity of drugs

17. ALTERATIONS DES MECANISMES HOMEOSTATIQUES CHEZ LE SUJET AGE Mauvaise tolérance aux variations brutales de volume plasmatique ? sensibilité aux diurétiques (surtout les diurétiques de l’anse, les plus puissants) Réduction de sensibilité des barorécepteurs ? haute fréquence d’hypotension orthostatique (attention à certains médicaments anti-hypertenseurs) Accroissement de la sensibilité des osmorécepteurs ? fréquence élevée d’hyponatrémie par sécrétion inappropriée d’ADH (favorisée éventuellement par certains médicaments)

18. Pharmacology and Aging Affect on functional status - Fall * assoc.with psychotropic drug use and hip fracture - Continence * urinary retention with antiCholinergics overflow incont with aagonist/block - Mental Functioning * confusion with antiCholinergics and psychotropes

19. DRUG SENSITIVITY IN ELDERLY PATIENTS Reduced responsiveness adrenergic drugs Unchanged responsiveness most drugs Increased responsiveness benzodiazepines warfarin

22. Low Body Water -> reduced vol. of dist. for polar drugs eg. Aminoglycosides, Digoxin High Fat Stores -> increased vol. of dist. for lipid soluble drugs eg. Phenytoin, Diazepam, Flurazepam

24. Changements physiologiques liés à l’âge ayant un effet sur la pharmacocinétique Elévation du pH gastrique Ralentissement de la vidange gastrique Réduction du flux sanguin splanchnique Réduction de la motricité gastro-intestinale Amincissement et réduction de la surface d’absorption Diminution de la taille corporelle totale Augmentation relative de la masse graisseuse totale Diminution des tissus actifs sur le métabolisme Diminution de l’eau corporelle totale Réduction de l’albumine plasmatique Augmentation légère et variable de l’ 1-acide glycoprotéine Réduction de la masse hépatique Redistribution du débit sanguin régional (foie, rein) Réduction de l’activité des enzymes microsomiques du foie Réduction de la filtration glomérulaire Réduction de la fonction tubulaire Adapté de Neve. Médecine gériatrique. Pratique quotidienne

25. Pharmacokinetics in the elderly Metabolism - Dependent on liver enzyme systems and hepatic blood flow - 65yo with 40-50% lower hepatic blood flow may lead to increase systemic concentrations - Biotransformation of drugs is relatively unaffected by age but …

26. Metabolism and CYP3A4 most abundant in liver (~30%) and gut metabolises >50% of all drugs substrates midazolam, simvastatin, nifedipine, cyclosporine, quinidine, numerous interactions (antimycotics) inducible by antiepileptics, rifampicin, steroids declines during ageing

27. Modifications liées à l’âge dans la clairance des benzodiazépines Influence de la voie métabolique hépatique Fonction mixte Conjugaison Phase I Phase II (oxydase) (glucuroconjugué) Diazépam ? Chlordiazépoxide ? Lorazépam = Oxazépam = Nitrazépam = Témazépam =

28. Pharmacokinetics in the elderly Renal elimination - Decline in GFR, renal plasma flow, secretion associated with old age - Studies have shown, declining renal function not inevitable outcome of aging. May represent effects of subclinical disease - Serum creatinin often underestimates decreased GFR because of decreased muscle mass - Digoxin, cimetidine and atenolol : common renal excreted drugs than may need dosage reduction

29. Médicaments nécessitant une adaptation posologique en cas d’insuffisance rénales Digoxine Aciclovir Cimétidine Lithium Vancomycine Aminosides Triméthoprime-sulphaméthoxazole La plupart des pénicillines La plupart des céphalosporines

31. Pharmacocinétique chez le sujet âgé Résumé L’absorption des médicaments est en général diminuée La distribution des médicaments est Accrue pour les médicaments liposolubles Réduite pour les médicaments hydrosolubles Le métabolisme des médicaments est Réduit pour les médications métabolisées par réactions de phase I (cytochromes) Inchangé pour les médications métabolisées par réactions de phase II (glucuronoconjugaison) L’excrétion rénale des médicaments diminue avec l’âge par Réduction de la filtration glomérulaire Réduction de la fonction tubulaire

32. PK and Drug effects in the Elderly Lower lean muscle mass Lower albumin Increased sensitivity Absorption generally the same Excretion and metabolism lower START LOW, GO SLOW!!

33. Factors modifying compliance Comprehension instructions labels cognition Dexterity Number of medications Side-effects

35. Sujet âgé et médicaments psychotropes Action sédative plus ou moins marquée Effet cardiodépresseur variable hypotension orthostatique chutes Effets anticholinergiques Syndromes parkinsoniens (antipsychotiques / neuroleptiques)

36. Médicaments principaux à effets anticholinergiques Alcaloïdes de la belladone Antidépresseurs tricycliques Antipsychotiques Antihistaminiques Antiarythmiques

37. Quelques médicaments induisant fréquemment des effets secondaires chez le sujet âgé

38. Choix du traitement le plus sûr dans différentes affections

39. La gestion du traitement médicamenteux : une solution par étapes

40. La gestion du traitement médicamenteux : une solution par étapes

41. Quelques règles de l’OMSconcernant la pharmacothérapie chez le sujet âgé

42. Quelques règles de l’OMS (suite) concernant la pharmacothérapie chez le sujet âgé

43. Pharmacotherapy in the elderly Conclusions Optimal drug use in elderly increasingly important as population ages and more medications come on market Drug prescribing one of the most important determinants of geriatric health and illness Impossible to completely eliminate ADR in elderly, but can be minimized and consequences recognized and managed

44. Pharmacotherapy in the elderly Conclusions The physician must be aware of the risk and contributing factors as well as techniques to minimize risk The considerations discussed will enable the clinician to maximize the benefit that can be achieved from drug therapy in older patients with reduction in risk for illnesses caused by such interventions