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Aly A. Misha’l MD, FACP Senior consultant in Medicine and Endocrinology Amman-Jordan 1 بسم الله الرحمن الرحيم.

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Presentation on theme: "Aly A. Misha’l MD, FACP Senior consultant in Medicine and Endocrinology Amman-Jordan 1 بسم الله الرحمن الرحيم."— Presentation transcript:

1 Aly A. Misha’l MD, FACP Senior consultant in Medicine and Endocrinology Amman-Jordan 1 بسم الله الرحمن الرحيم

2 Senility and frailty was described in the Glorious Qur’an in a sense of physical weakness and decline in capabilities, implying significant needs for care, sympathy and mercy. 2

3 ”.... وقد بلغت من الكبر عتياً“ “…. And I have grown quite decrepit from old age” The Glorious Qur’an, Chapter19: Verse 8 3

4 ” قال ربي إني وهن العظم مني.....“ “ O my lord! Infirm (Brittle) indeed are my bones …” The Glorious Qur’an, Chapter 19: Verse 4. 4

5 ” ومنكم من يردُّ إلى أرذل العمل لكي لا يعلم بعد علم شيئاً“ “Some of you are sent back to feeble age, so that they know nothing after what they have known” The Glorious Qur’an, Chapter 16: Verse 70 5

6 Caring for sick elderly subjects, as part of medical practice, is an act of worship, human and religious duty, that the whole society (Ummah) will be held sinful if it fails to induce and support some of its members to become caring medical professionals (Fardh Kifayah). 6

7 Optimizing medical care is a cornerstone in both Itqan (perfection) and Ihsan (excellence) 7

8 Optimizing drug therapy is a cornerstone of proper caring for older individuals. 8

9 Basic parameters: 1.Deciding whether a drug is indicated. 2.Choosing the most appropriate drug. 3.Determining dose schedules. 9

10 4. Monitoring for effectiveness and toxicity. 5. Educating the patient (and family) about expected side effects. 10

11 6.Educating the patient (and family) about indications for seeking consultation. 11

12 7. Always inquire about the use of over the counter drugs, herbal preparations and dietary supplements. 12

13 8. The possibility of an adverse drug event should always be borne in mind when evaluating an elderly individual. 13

14 Any new symptom should be considered drug-related until proven otherwise. 14

15 Geriatric Clinical pharmacology: Addresses:  Pharmacokinetics: i.e, absorption, distribution, metabolism and excretion.  Pharmacodynamics: i.e, the physiologic affects of the drug. 15

16  Adverse drug reactions.  Drug interactions.  Rational drug therapy for older persons. 16

17 OLD AGE AND PHARMACOKINETICS 17

18  Age related increase in the proportion of body fat: causes increase in volume of distribution for lipid-soluble drugs: e.g: benzodiazepines. 18

19  Age-related decrease in lean body mass: causes 10-15% decrease in total body water: The volume of distribution declines for hydrophilic drugs e.g, alcohol. 19

20  Plasma albumen concentration decreases in elderly malnorished subjects, especially those with advanced cancer. 20

21 The plasma-binding of some drugs decreases and the unbound fraction may exceed 50%  increase free drug concentrations and toxicity. e.g, Salicylate, Naproxen, Acetazolamide, Valproate. 21

22  Age-related decrease in liver mass: 20-50%: during the age span up to 80 years.  Decreased amount of drug- metabolizing enzymes. 22

23 Associated with that, there is gradual decrease of hepatic blood flow.  Decrease in clearance of drugs. 23

24  Decrease in elimination by conjugation of some drugs by up to 25%. e.g. Theophylline. 24

25  Decreased first-pass metabolism of some drugs that are highly extracted by the liver. e.g. Labetalol, Propranolol, Verapamil and Morphine: This results in decreased systemic bioavailability and decreased concentration. 25

26 Older smokers: Decreased hepatic metabolizing enzymes: increased mortality in older smokers. 26

27 Malnutrition: e.g. in cancer patients with anorexia. Impairment of drug metabolism. Adjusting of dosage (esp. cancer drugs) is important. 27

28 Old frail subjects and decreased clearance of acctominophen: Up to 42% in one study. 28

29 Warfarin: Age-related decline in liver volume. decrease in warfarin dose requirement: may start at age of 50 years. 29

30 Renal function: Renal mass decreases by 25-30% across the age span. 30

31 Renal blood flow decreases by 1% per year after age of 50 years. 31

32 GFR decreases by 35% in healthy individuals between ages 20 and 90 years. 32

33 In some individuals: this decline does not occur! 33

34 This GFR decrease affects the clearance of drugs that are secreted or filtered by the kidney. 34

35 PHARMACODYNAMICS 35

36 High affinity receptors are diminished. Decline in receptor- effectar coupling. e.g: I.V isoproterenol to increase heart rate in older patients: Compromised More doses are needed. 36

37 Sensitivity to psychoactive drugs is greater in older persons: e.g anxiolic drugs and hypnotics. 37

38 Pain management for cancer patients: e.g Morphine and pentazocine. Duration of pain relief is prolonged with increasing age. Probably due to decreased volume of distribution. 38

39 Anesthesia: Increased brain sensitivity to I.V fentanyl and altentanil. 39

40 ISSUES IN DRUG PRESCRIBING FOR THE ELDERLY 40

41 Quality of Drug Prescribing: Several dimensions:  Avoidance of inappropriate medications.  Appropriate utilization of indicated drugs. 41

42  Monitoring for side effects, and drug levels.  Avoidance of drug-drug interactions.  Involvement of the patient and integration of his/her values. 42

43 Indicator titleDescriptionRationale Monitoring warfarin therapy When warfarin is prescribed, international normalized ratio (INR) should be monitored using standard protocols. Older adults are at high risk for drug toxicity that can be identified earlier if there is close monitoring for agents with a narrow therapeutic range. Monitoring loop diuretic therapy When loop diuretic therapy is prescribed, electrolytes should be checked within one week after initiation and at least annually Risk of hypokalemia due to diuretic therapy 43

44 Indicator titleDescriptionRationale hypoglycemic agent When prescribing an oral hypoglycemic agent, chlorpropamide should not be used. This therapy has a prolonged half- life that can result in serious hypoglycemia and is more likely than other agents to cause the syndrome of inappropriate secretion of antidiuretic hormone. Avoid drugs with strong anticholinergic properties Do not prescribe drug therapies with a strong anticholinergic effect, if alternative therapies are available. These therapies are associated with adverse events such as confusion, urinary retention, constipation, and hypotension. 44

45 Indicator titleDescriptionRationale Avoid barbituates If an older adult does require the therapy for control of seizures, do not use barbiturates. These therapies are potent central nervous system depressants, have a low therapeutic index, are highly addictive, cause drug interactions, and are associated with an increased risk for falls and hip fracture. Avoid meperidine as an opioid analgesic When analgesia is required, avoid use of meperidine. This therapy is associated with an increased risk for delirium and may be associated with the development of seizures. Monitor renal function and potassium in patients prescribed angiotensin- converting enzyme inhibitors If ACE inhibitor therapy is initiated, potassium and creatinine levels should be closely monitored. Monitoring may prevent the development of renal insufficiency and hyperkalemia. 45 Knight, El, Avorn, Ann Intern Med 2001; 135:703.

46 In evaluating subjects on multiple medications, always consider:  Over-the-counter drugs.  Herbal preparations.  Supplements. 46

47 Around 50% of older patients use 5 or more medications. 47

48 Older individuals are at greater risk for adverse drug events (ADE), due to changes in pharmacokinatics and pharmacodynamics. 48

49 Polypharmacy increases the potential of drug-drug interactions. 49

50 Polypharmacy is a risk factor for falls and hip fractures. 50

51 Polypharmacy increases the risk of “Prescribing Cascades”: When an ADE is misinterpreted as a new medical condition. 51

52 Initial drug therapyAdverse drug eventSubsequent drug therapy Antipsychotics Extrapyramidal signs and symptoms Antiparkinsonian therapy Cholinesterase inhibitorsUrinary incontinenceIncontinence treatment Thiazide diureticsHyperuricemiaGout treatment NSAIDsIncreased blood pressureAntihypertensive therapy 52 Rochon, PA, Gurwitz, JH. BMJ 1997; 315:1096 Gill, SS, Mamdani, M, Naglie, G, et al. Arch Intern Med 2005;

53 Associated with multiple adverse effects in older individuals:  Memory impairment.  Confusion, hallucinations.  Dry mouth.  Blurred vision. 53

54  Constipation, nausea.  Urinary retention.  Impaired sweating.  Tachycardia.  Can precipitate acute glaucoma. 54

55 3points2 points1 Point Amitriptyline hydrochloride Amantadine hydrochloride Carbidopa-levodopa Atropine productsBaclofenEntacapone Benztropine mesylateCetirizine hydrochlorideHaloperidol CarisoprodolCimetidineMethocarbamol Chlorpheniramine maleate Clozapine Metoclopramide hydrochloride Chlorpromazine hydrochloride Cyclobenzaprine hydrochloride Mirtazapine Cyproheptadine hydrochloride Desipramine hydrochloride Paroxetine hydrochloride 55

56 3points2 points1 Point Dicyclomine hydrochloride Loperamide hydrochloride Pramipexole dihydrochloride Diphenhydramine hydrochloride LoratadineQuetiapine fumarate Fluphenazine hyrochloride Nortriptyline hydrochloride Ranitidine hydrochloride Hydroxyzine hydrochloride and hydroxyzine pamoate OlanzapineRisperidone Hyoscyamine productsProchlorperazine maleateSelegiline hydrochloride Imipramine hydrochloride Pseudoephedrine hyrochloride-triprolidine hydrochloride Trazodone hydrochloride Meclizine hydrochlorideTolterodine tartrateZiprasidone hydroch 56

57 3points2 points1 Point Oxybutynin chloride Perphenazine Promethazine hydrochloride Thioridazine hydrochloride Thiothixene Tizanidine hydrochloride Trifluoperazine hydrochloride 57 Rudolph, JL, Salow, MJ, Angelini, MC, McGlinchey. Arch Intern Med 2008;

58 Commonly used in nursing homes: 20% individuals were found using at least one inappropriate drug. 58

59 TherapyTherapy descriptionReason for concern Always avoid BarbituratesHypnoticHighly addictive ChlorpropamideOral antihyperglycemic Long half-life, inappropriate ADH secretion MeprobamateHypnoticHighly addictive Pethidine (Meperidine)OpioidIneffective orally 59

60 TherapyTherapy descriptionReason for concern Rarely appropriate CarisoprodolSkeletal muscle relaxant Strong anticholinergic properties, sedation and weakness DiazepamBenzodiazepineLong half-life 60

61 TherapyTherapy descriptionReason for concern Some indication (but often misused) AmitriptylineAntidepressant Strong anticholinergic properties and sedation DiphenhydramineAntihistamine Strong anticholinergic properties DoxepinAntidepressant Strong anticholinergic properties and sedation IndomethacinNSAID More CNS adverse effects than other NSAIDs MethyldopaAntihypertensive Can cause bradycardia and exacerbate depression OxybutyninAntimuscarinic Strong anticholinergic properties, sedation and weakness ReserpineAntihypertensive Can induce depression and sedation TiclopidinePlatelet inhibitorPoor adverse effect profile 61 Rochon, P, Lane, c, Bronskill, S, et al. Drugs aging 2004; 21:939

62 DRUG-DRUG INTERACTIONS: ONE MAJOR PROBLEM OF POLYPHARMACY 62

63 Older adults are particularly vulnerable: e.g: Increased risk of bleeding with warfarin therapy with co- administration of NSAIDs, SSRIs, Omeprazole, lipid-lowering agents, amiodarone and fluorouracil. 63

64 Risk of hypoglycemia: Increased with concomitant use of glyburide and co-trimoxazole. 64

65 Digoxin toxicity increases with concomitant use of clarithromycin 65

66 Treating physicians should review all existing medications in every patient’s visit. 66

67 Approach Review current drug therapy Discontinue potentially unnecessary therapy Consider adverse drug events as a potential cause for any new symptom Consider non-pharmacological approaches Substitute with safer alternatives Reduce the dose Use beneficial therapies when indicated 67 Rochon, P, JH, Gurwitz. The Lancet 1995;346:32.

68 SUMMARY AND RECOMMENDATIONS 68

69  The possibility of ADE should always be borne in mind. Any new symptoms should be considered drug-related until proven otherwise. 69

70  Physicians must always review all medications used. Special attention to non- prescription drugs, herbs and supplements. 70

71  Various criteria sets exist in the literature that identify medications to be avoided, or prescribed with caution. 71

72  Physicians should avoid under- utilization, as much as over- utilization of drugs. 72

73  ADEs result in 4 times as many hospitalizations in older compared with younger adults. 73

74  Causes of PREVENTABLE ADEs include, among others: Prescribing cascades, Drug-drug interactions And inappropriate drug doses. 74

75  Follow a step-wise approach to prescribing for older adults. 75

76 والله نسأل أن يعلمنا ما ينفعنا وأن ينفعنا بما علمنا ويزيدنا علما... 76


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