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Denutrition and drugs

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  • c/mes documents/IATRO/ANM DU 22_11_05/acc médic comment prév PQV2
  • Prescriptions thérapeutiques utiles et inutiles
  • Prescriptions thérapeutiques utiles et inutiles
  • Prescriptions thérapeutiques utiles et inutiles
  • Prescriptions thérapeutiques utiles et inutiles
  • c/mes documents/IATRO/ANM DU 22_11_05/acc médic comment prév PQV2
  • Queneau

    1. 1. 2011 International Seminar on Geriatrics (Athens, April 1-3 2011) Denutrition and drugs in the elderly Pr. Patrice QUENEAU De l’Académie Nationale de Médecine
    2. 2. <ul><li>Iatrogenesis </li></ul><ul><li>Changes in the elderly </li></ul><ul><li>Examples of at-risk situations </li></ul>2011
    3. 3. INTRODUCTION <ul><li>Iatrogenesis : any disease or adverse event caused by a medical intervention within the health care system . </li></ul><ul><li>The term does not prejudge in any way an error, fault or negligence : some risks are unavoidable, others not. </li></ul><ul><li>In France, the Act of March 4 2002 allows to compensate a patient in the absence of fault (no-fault therapeutic hazard). </li></ul><ul><li>In Geriatrics, the mere decision to hospitalize can lead to undue loss of autonomy. </li></ul><ul><li>Iatrogenesis can result from the action of any caregiver : physician, therapist/kinesiologist, hospital porters ... </li></ul>2011
    4. 4. INTRODUCTION 2011 <ul><li>Drug-induced iatrogenesis : </li></ul><ul><li>Adverse effects without therapeutic misuse , or no fault hazard </li></ul><ul><li>Adverse effects with therapeutic misuse </li></ul><ul><ul><li>Whether this &quot;misuse&quot; is caused by: </li></ul></ul><ul><ul><ul><ul><li>The physician </li></ul></ul></ul></ul><ul><ul><ul><ul><li>By extension, other caregivers (notably the pharmacist or the nurse) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Or the patient himself , through inappropriate self-medication or poor compliance with treatment </li></ul></ul></ul></ul>
    5. 5. IATROGENESIS IN THE ELDERLY <ul><li>The adverse effects of drugs are: </li></ul><ul><ul><li>More frequent, from 3 to 20 % </li></ul></ul><ul><ul><li>Involved in 5 to 10 % (even more) of hospitalizations </li></ul></ul><ul><li>The reasons for hospitalization are: </li></ul><ul><ul><li>Dehydration with functional renal failure (RF) </li></ul></ul><ul><ul><li>Orthostatic hypotension with falls </li></ul></ul><ul><ul><li>Confusional states </li></ul></ul><ul><ul><li>Gastrointestinal bleeding </li></ul></ul><ul><li>They are preventable in part: inadequate dosage, drug interactions, interactions with diseases => concept of misuse or inappropriate prescriptions. </li></ul><ul><li>Certain adverse drug reactions are unpredictable or difficult to dissociate from the desired therapeutic action. </li></ul>2011
    6. 6. <ul><li>Polypathology </li></ul>2011 Polymedication Automedication Poor compliance Aging Adverse effect of the drug Inadequate drug concentration Altered organ response Reduction of functional capacity Homeostatic dysregulation
    7. 7. CONCEPT OF &quot;INAPPROPRIATE DRUG PRESCRIPTION&quot; <ul><li>Developed by Anglo-Saxon authors [Beers] . </li></ul><ul><li>It corresponds to an insufficient consideration of drugs and/or diseases leading to prescribe a drug that is not optimal between the expected return and the risk incurred. </li></ul><ul><li>This can be : inappropriate indications (risk factors in the very elderly), excessive risk taking (AVK in the very elderly), excessive dosages, excessive length of prescription. </li></ul>2011
    8. 8. <ul><li>Iatrogenesis </li></ul><ul><li>Changes in the elderly </li></ul><ul><li>Examples of at-risk situations </li></ul>2011
    9. 9. AGING AND CHANGES IN BODY SIZE <ul><li>Decrease in lean mass and increase in fat mass </li></ul><ul><li>Frequency of hypo- albuminemia </li></ul>2011
    10. 10. CHANGES IN COMPARTMENTAL DISTRIBUTION IN THE ELDERLY <ul><li>Compartments </li></ul><ul><ul><li>Decrease in total body water </li></ul></ul><ul><ul><ul><li>60 % at age 20 50 % at age 85 </li></ul></ul></ul><ul><ul><li>Increase in fat mass </li></ul></ul><ul><ul><li>18 % at age 20 36 % at age 85 </li></ul></ul><ul><ul><li>Decrease in lean mass </li></ul></ul><ul><ul><li>Decrease in active cell mass  </li></ul></ul><ul><ul><ul><li> Membrane transport capacity + </li></ul></ul></ul><ul><ul><ul><li> Enzymatic capacity (liver – kidney especially) </li></ul></ul></ul>2011
    11. 11. CHANGES IN BODY WATER COMPARTMENTS WITH AGING FAT MASS 26 kg LEAN MASS 44 kg LEAN MASS 55 kg FAT MASS 15 kg 42 L of water 35 L of water 20 yrs - 70 kg Water : 60% of total weight / 85 yrs - 70 kg Water : 50% of total weight 2011
    12. 12. CHANGES IN DRUG DISTRIBUTION LINKED TO BODY SIZE <ul><li>Increase in fat mass at the expense of muscle mass (1/3 greater at age 75 than at age 30) </li></ul><ul><ul><li> volume of lipophilic molecules due to a greater distribution in adipose tissue (antidepressant, anaesthetic, Central nervous system) </li></ul></ul><ul><ul><li>Storage in fat tissue, replenishing prolongation of half-life </li></ul></ul><ul><ul><li> volume of hydrophilic molecules (paracetamol, digoxin…), resulting in higher serum concentrations at equal dosage, hence possibility of adverse effects </li></ul></ul>2011
    13. 13. <ul><li>Hypoalbuminemia will cause a decrease in acidic binding (aspirin, warfarin, phenytoin) -> risk of overdosing </li></ul><ul><li>Beware in case of disease reducing the synthesis of albumin : stress, denutrition, hypercatabolism </li></ul><ul><li>Increased alpha 1 acid glycoprotein (orosomucoids) leading to increased binding capacity of basic molecules -> risk of underdosing = marginal situation </li></ul>CHANGES IN DRUG DISTRIBUTION LINKED TO BODY SIZE 2011
    14. 14. AGE-RELATED CHANGES IN THE DISTRIBUTION VOLUME (Vd) OF CERTAIN DRUGS 2011 Vd  Vd  Vd  Furosemide Amikacin Gentamycin Isoniazid Paracetamol Warfarin Alprazolam Diazepam Lidocaine Acetyl-salicylic acid Anthracyclines Morphine Digoxin Cisplatin
    15. 15. DENUTRITION AND CREATININE PRODUCTION 2011 <ul><li>In the elderly malnourished, the serum creatinine assay is insufficient to assess renal function. </li></ul><ul><li>Influence of creatinine levels on a number of parameters </li></ul><ul><ul><li>Diet (low in protein) </li></ul></ul><ul><ul><li>Muscle mass (+++) </li></ul></ul><ul><ul><li>Physical exercise (sedentary  reduction) </li></ul></ul><ul><ul><li>Certain drug treatments </li></ul></ul><ul><ul><li>Certain pathological conditions </li></ul></ul><ul><li>Clearance estimation is essential: Cockcroft formula, study MDRD formula </li></ul>
    16. 16. PRACTICAL ASSESSMENT OF GLOMERULAR FILTRATION RATE Rev Med Int 2008 ; 29 : 364 - 69 Comparative study of Carbonnel et al. 81 patients Mean age 82.3  7.0 Mean albumin 33.3  5.2 Mean weight 59.6  14.8 120 40 80 0 Cockcroft & Gault 42.1  17.1 Creat / Urine cl. 33.7  21.3 MDRD 49.9  16.4 2011
    17. 17. <ul><li>Iatrogenesis </li></ul><ul><li>Changes in the elderly </li></ul><ul><li>Examples of </li></ul><ul><li>at-risk situations </li></ul>2011
    18. 18. SOME EXAMPLES OF AT-RISK SITUATIONS <ul><li>Anticoagulants </li></ul><ul><li>Renal clearance drugs </li></ul><ul><li>Psychotropic drugs </li></ul><ul><li>Oral antidiabetic drugs </li></ul><ul><li>Antimitotic drugs </li></ul>2011
    19. 19. ANTIVITAMINS K AVK <ul><li>Currently, 1.4 % of French population on AVK ! </li></ul><ul><li>(1 200 000 patients) </li></ul><ul><li>Fluindione (Previscan®) 77 % ; Acenocoumarol (Sintrom®) 16 % ; Warfarin (Coumadin®) 7 % </li></ul><ul><li>Primary cause of hospitalization for side effects : </li></ul><ul><li> </li></ul><ul><li>Major 2.4 - 5 % / yr </li></ul><ul><li>Minor 6 - 10 % / yr </li></ul><ul><li>Elderly patient Greater sensitivity due to stronger inhibition of synthesis of factors II - VII - IX - X at identical serum concentrations </li></ul><ul><li>[Ann Int Med 2001 ; 135 : 393 - 400] </li></ul>2011
    20. 20. ANTIVITAMINS K AVK <ul><li>Doses required for INR 2 - 3 </li></ul><ul><li> Age Warfarin dosage (mg) </li></ul><ul><li>40 - 49 yrs 7.3 (6.2 – 8.3) </li></ul><ul><li>50 - 59 yrs 5.5 (5 - 6) </li></ul><ul><li>60 - 69 yrs 4.3 (4 – 4.5) </li></ul><ul><li>70 - 79 yrs 3.9 (3.7 – 4.1) </li></ul><ul><li>  80 yrs 3.3 (3 – 3.6) </li></ul><ul><li>[JAGS 2002 ; 50 : 1439 - 55] </li></ul><ul><li>Longer normalization of INR if elevated </li></ul><ul><li>Sometimes with 1 to 2 mg of Warfarin, INR can be between 6 and 10 ! </li></ul>2011
    21. 21. ANTIVITAMINS K AVK <ul><li>Hemorrhagic risk factors under AVK </li></ul><ul><li>[Am J Med 1998 ; 105 : 91 - 9] </li></ul><ul><li>Age > 65 yrs - Diabetes </li></ul><ul><li>ATD stroke, myocardial infarction, gastrointestinal bleeding </li></ul><ul><li>Hematocrit < 30 % </li></ul><ul><li>Renal failure with creatinine > 150 mcmol/L </li></ul><ul><li>> 3 medications : drug interactions </li></ul><ul><li>[BMJ 2003 ; 326 : 153 - 56] </li></ul><ul><li>  INR : Paracetamol - PPI - Amiodarone - IRS - Aspirin - Antibiotics </li></ul><ul><li> Hence, systematic INR after introduction </li></ul><ul><li>or discontinuation of any drug </li></ul>2011
    22. 22. Strong corrélation ( 80 %) between % of Adverse Drug Events and number of drugs (study in Emergency Units) P. Queneau, Drugs Safety, 2006 P. Queneau
    23. 23. PSYCHOTROPIC DRUGS <ul><li>BENZODIAZEPINES </li></ul><ul><ul><li>Specific risks </li></ul></ul><ul><ul><ul><li>Present in 25 % of elderly subjects with risk of hip fracture x 2 </li></ul></ul></ul><ul><ul><ul><li>The decline in hepatic redox capacity (Phase I) and renal elimination increases half-life of certain BZDs by 50 to 100 % between age 30 and 80 years. </li></ul></ul></ul><ul><ul><ul><li>Increased sensitivity to central effects : sedation, confusion, impaired memory </li></ul></ul></ul><ul><ul><li>Recommendations </li></ul></ul><ul><ul><ul><li>Use BZD with short half-life+++ : oxazepam (Seresta), alprazolam (Xanax) </li></ul></ul></ul><ul><ul><ul><li>Reduce posology by two or three+++ </li></ul></ul></ul>2011
    24. 24. <ul><li>EXAMPLE OF THE METABOLISM OF BENZODIAZEPINES </li></ul>MALETTA G. Geriatrics 1991 ; 46 : 40 - 60 SHORR R. Drugs and Aging 1994 ; 4 : 9 - 20 G + Glucuronidation (phase II) O = Oxydation (phase I) 2011 OXAZEPAM Seresta ALPRAZOLAM Xanax DIAZEPAM Valium Half-life Adult Short (< 10 H) 7 H Intermediate 10 -> 20 H 11 H Long (> 20 H) 46 H Minimum duration of &quot;steady state&quot; 2 d 2 d 10 d Active metabolite No  O (G) (Alpha OH Alprazolam) + + (O) Desmethyldiazepam 29 to 223 H Temazepam 8 to 38 H Half-life Elderly 8 H 19 H 90 H
    25. 25. PSYCHOTROPIC DRUGS <ul><li>LITHIUM </li></ul><ul><ul><li>Risk of overdosing </li></ul></ul><ul><ul><ul><li>By interaction with diuretics </li></ul></ul></ul><ul><ul><li>Recommendation </li></ul></ul><ul><ul><ul><li>Lower residual rate </li></ul></ul></ul><ul><li>NEUROLEPTICS </li></ul><ul><ul><li>Rise in the active free fraction via reduction in protein binding </li></ul></ul>2011
    26. 26. <ul><li>Particular risks </li></ul><ul><ul><ul><li>Long acting hypoglycemic sulfonamides : sulfonylurea Ozidia ®, Glucidoral® </li></ul></ul></ul><ul><ul><ul><li>Insulin delay </li></ul></ul></ul><ul><ul><ul><li>Strong binding of sulfonamides to plasma proteins - > increase of their efficacy </li></ul></ul></ul><ul><li>Recommendations </li></ul><ul><ul><ul><li>Short half-life sulfonamides </li></ul></ul></ul><ul><ul><ul><li>Transition to Insulin </li></ul></ul></ul>ANTIDIABETIC DRUGS 2011
    27. 27. ANTINEOPLASTIC DRUGS <ul><li>Risks linked to decrease in protein binding </li></ul><ul><ul><li>Reduction of transport proteins </li></ul></ul><ul><ul><ul><li>Albuminemia : 48 g/l at age 20 36 g/l at age 85 </li></ul></ul></ul><ul><ul><li>Active free fraction of the drug is increased </li></ul></ul><ul><li>Recommendations : dosage adjustment related to the increase in free fraction+++ </li></ul><ul><li>Taxanes, Anthracyclines </li></ul><ul><li> Methotrexate, Vinca alkaloids </li></ul><ul><li> Epirubicin, Etoposide, Teniposide </li></ul>2011
    28. 28. CONCLUSION MAJOR DRUGS INVOLVED IN CASE OF DENUTRITION <ul><li>Drugs with to achieve efficacy without side effects or those susceptible to affect the fate of other drugs. </li></ul><ul><li>The classic agents are oral anticoagulants, NSAIDs, aminoglycosides, corticosteroids, opiates, antipsychotics, immunosuppressants… </li></ul><ul><li>From a practical standpoint, all antineoplastic drugs have a narrow therapeutic margin and are at risk in case of denutrition. </li></ul>2011
    29. 29. Evidence based medicine: what it is and what it isn ’ t L ’Evidence-Based Medicine by the Working Goup JAMA 1992, 268 (17): 2420-5 avid L Sackett, William M C Rosenberg, J A Muir Gray, R Brian Haynes, W Scott Richardson+Author Affiliations <ul><li>«  the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients . » </li></ul>
    30. 35. Limites (et critiques) de l’EBM ? <ul><li>Chaque malade est UNIQUE </li></ul><ul><li>> pas de malade « MOYEN » </li></ul><ul><li>Essais randomisés disponibles pour une infime proportion des décisions prises quotidiennement par un médecin </li></ul><ul><li>Publications sont anglo-saxonnes le plus souvent </li></ul><ul><li>Etudes avec résultats négatifs : rarement publiées </li></ul><ul><li>Efficacité : routine ≠ conditions expérimentales </li></ul><ul><li>> la médecine : SCIENCE ET ART </li></ul>
    31. 36. <ul><li>l’ EBM : « l’utilisation consciencieuse et judicieuse des meilleures données actuelles de la recherche cliniqu e </li></ul><ul><li>dans la prise en charge </li></ul><ul><li>personnalisée de chaque patient   » </li></ul>6-7-8 septembre 2007 P. Queneau, J. Doucet, F. Paille L ’Evidence-Based Medicine Working Goup JAMA 1992, 268 (17): 2420-5
    32. 37. UNFRACTIONATED HEPARIN UFH <ul><li>By IV / subcutaneous (Calciparin) </li></ul><ul><li>Anti Xa and Anti II activity or equivalent - TCA 1.5 to 2.5 / control / 6 h after injection </li></ul><ul><li>Risk factors for bleeding complications </li></ul><ul><li>Anti Xa dosage > 0.8 UI/ml </li></ul><ul><li>Low weight and hypoalbuminemia </li></ul><ul><li>Coprescription of Aspirin </li></ul><ul><li>Surgery or trauma < 10 d </li></ul><ul><li>Abnormal homeostasis </li></ul><ul><li>Age [> 72 yrs Arch Int Med 1996] </li></ul><ul><li>Renal function -> low level </li></ul><ul><li>Equal efficacy of continuous IV route / subcutaneous route / 12 h </li></ul><ul><li>Recommendation  2500 UI / 0.1 ml / 10 kg / 12 h </li></ul>2011
    33. 38. LOW MOLECULAR WEIGHT HEPARIN LMWH <ul><li>Anti Xa activity especially </li></ul><ul><li>Predictable activity based on weight </li></ul><ul><li>Renal elimination, hence increased risks </li></ul><ul><ul><li>if long half-life LMWH </li></ul></ul><ul><li>AFSSAPS 2000: Preventive treatment not recommended </li></ul><ul><ul><li>if Creat cl < 30 ml/mn </li></ul></ul><ul><li>Risk factors : bleeding complications </li></ul><ul><ul><li>Anti Xa dosage > 0.8 UI/ml </li></ul></ul><ul><ul><li>Reduced weight </li></ul></ul><ul><ul><li>Renal function < 30 ml/min + + </li></ul></ul><ul><ul><li>Treatment > 10 d </li></ul></ul>2011

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