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Geriatrics pharmacology

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Geriatrics pharmacology

  2. 2.  20% of hospitalizations for those >65 are due to medications they’re taking
  3. 3.  Alzheimer`s disease  Parkinsonism  Stroke  Vascular dementia  Visual impairment specially cataracts and macular degeneration  Atherosclerosis  Arthritis  Heart failure  Fractures  Cancer  Diabetes  Heart failure
  4. 4.  Physiologic change ◦ Decreased gastric acidity ◦ Decreased gastrointestinal blood flow ◦ Delayed gastric emptying ◦ Slowed intestinal transit time  General clinical effect ◦ None on passive diffusion or bioavailability for most drugs ◦ Decreased active transport: Decreased bioavailability for some drugs ◦ Decreased first-pass effect: Increased bioavailability for some drugs
  5. 5.  Decreased Total body water ◦ Increased Plasma Conc. of water soluble drugs ◦ Lower doses are required: Lithium, digoxin, ethanol, etc  Decreased Lean body mass ◦ Increased Volume Distribution, Longer (t½) of water soluble drugs ◦ Accumulation into fat of lipid soluble drugs: Benzos, etc  Decreased Serum Albumin ◦ Increased unbound fraction of highly protein bound drugs ◦ Binds acidic drugs: warfarin, phenytoin, digitalis, etc  Decreased Alpha1 Acid glycoprotein ◦ Increased unbound fraction of highly protein bound drugs ◦ -Binds basic drugs: lidocaine and propranolol, etc
  6. 6.  Difficult to predict, depends on General health & nutritional status  Use of alcohol, medications Long term exposure to environmental toxins/pollutants  Aging causes decreased liver mass/ hepatic blood flow Delayed/reduced metabolism of drugs Higher plasma levels Greatest changes in phase 1 reaction those carry out microsomal p450 enzyme system Decline in liver ability to recover from injury  Lower serum protein levels Loss of protein binding  Idiosyncratic reactions
  7. 7.  Metabolic clearance of drugs by the liver may be reduced due to: ◦ decreased hepatic blood flow ◦ decreased liver size and mass  Examples: morphine, meperidine, metoprolol, propranolol, verapamil, amitryptyline, nortriptyline
  8. 8.  Determined ◦ Primarily by renal function ◦ Declines with age and is worsened by co-morbidities ◦ Decline is not reflected in an equivalent rise in serum creatinine since creatinine production is reduced due to lower muscle mass
  9. 9.  Physiologic change ◦ Decreased GFR ◦ Decreased renal blood flow ◦ Decreased renal mass  General clinical effect ◦ Decreased clearance, Increased (t½) of renally eliminated drugs
  10. 10.  Creatinine clearance (CrCl) is used to estimate glomerular rate  Serum creatinine alone not accurate in the elderly ◦  lean body mass  lower creatinine production ◦  glomerular filtration rate  Serum creatinine stays in normal range, masking change in creatinine clearance
  11. 11.  Measure ◦ Time consuming ◦ Requires 24 hr urine collection  Estimate ◦ Cockroft Gault equation (IBW in kg) x (140-age) ------------------------------ x (0.85 for females) 72 x (Scr in mg/dL)
  12. 12.  Pharmacodynamic changes in the elderly have been less extensively studied  Evidence of enhanced end-organ responsiveness or “sensitivity” to medications with aging  Enhanced “sensitivity” may be due ◦ Changes in receptor affinity ◦ Changes in receptor number ◦ Post-receptor alteration ◦ Age-related impairment of homeostatic mechanisms Example: decreased baroreceptor reflexes
  13. 13.  Age-related changes: ◦  sensitivity to sedation and psychomotor impairment with benzodiazepines ◦  level and duration of pain relief with narcotic agents ◦  drowsiness with alcohol ◦  sensitivity to anti-cholinergic agents ◦  cardiac sensitivity to digoxin
  14. 14.  Cognitive changes associated with vascular and other pathology  Economic stresses with greatly associated with reduced income or due increased expenses due to illness  Loss of spouse
  15. 15.  Positive relationship between number of drugs taken and incidence  Overall incidence is estimated to be at least twice that in the younger population  Prescribing errors ◦ Polypharmacy ◦ Drug interactions with other prescriptions ◦ Unawareness of age related physiologic changes  Drug usage errors ◦ “Hidden ingredients”: OTCs
  16. 16. Factors contributing to adverse drug reactions in elderly patients Polypharmacy How many prescription medications are too many? >4 or >6 Many elderly people receive 12 medications per day Heart, kidney, liver, thyroid
  17. 17.  Economic factors ◦ May have to choose between food and medications  OTCs instead of expensive doctor visits  Use of outdated medications  Use of home remedies  Share medications  Nutritional status may affect how body metabolizes medications
  18. 18.  Concurrent use of multiple medications ◦ >65 = 12% of population ◦ Consume 30% of all prescription drugs [average person takes 4-5 prescription meds] ◦ Consume 40% of OTCs  Excessive use of drugs  Overdose of a drug
  19. 19.  Risks of problems: ◦ Medication errors  Wrong drug, time, route ◦ Adverse effects from each drug  Polypharmacy primary reason for adverse reactions ◦ Adverse interactions between drugs
  20. 20.  CNS drugs ◦ Sedative-hypnotics: Benzodiazepines and barbiturates ◦ Analgesics: Opioids ◦ Antipsychotic, antidepressants: Haloperidol, lithium, TCAs  Cardiovascular drugs ◦ Antihypertensives: Thiazides, beta-blockers  Antiarrhythmic drugs ◦ Quinidine and procainamide:  clearance and  (t½)  Antimicrobial drugs ◦ Beta-lactams and aminoglycosides:  clearance  Anti-inflammatory drugs ◦ NSAIDs: GI bleed and irritation
  21. 21. Half life of many drugs benzodiazepine and barbiturates increases 50-150% between age 30 and 70 Age related decline in renal and liver function both contribute to to the reduction in elimination of these compounds . Lorazepam and oxazepam may be less affected by these change. It is generally believed that the elderly vary more in their sensitivity to these sedatives on PD basis as well. Adverse reactions like Ataxia and motor impairment mostly present
  22. 22.  Elderly are often markedly more sensitive to the respiratory effect of these agents because of age related changes in respiratory function like airways and tissues become less elastic .
  23. 23.  Narcotic analgesics ◦ Respiratory depression ◦ Constipation ◦ Urinary retention ◦ Hypotension, ◦ dizzines ◦ confusion
  24. 24.  Phenothiazines and Heloperidol have been heavily used in the management of variety of psychiatric diseases in elderly .  Useful in treatments of some symptoms associated with delirium, dementia, agitation, combativeness however their use is not satisfactory in geriatrics conditions.  Much of these improvements are simply reflect the sedative effects  Phenothiazines often induce orhtostatic hypotension because of their a-adrenergic blocking effects.
  25. 25.  Antipsychotics ◦ Jaundice ◦ Extrapyramidal symptoms ◦ Sedation, dizziness (can lead to falls) ◦ Orthostatic hypotension ◦ Scaling skin on exposure to sunlight (phenothiazines)
  26. 26.  Tricyclic antidepressants ◦ Dry mouth ◦ Constipation ◦ Blurred vision ◦ Postural hypotension ◦ Dizziness ◦ Tachycardia ◦ Urinary retention
  27. 27.  Antihypertensive drugs  Systolic blood pressure increases with age in western countries and in most culture in which salt intake is high  Drugs used for it are Thiazides ,calcium channel blocker ,beta blockers etc  ADRS related to these drugs ◦ Dizziness and falls ◦ Orthostatic hypotension
  28. 28.  Diuretics ◦ Fluid/electrolyte disorders ◦ Dehydration ◦ Hypotension ◦ Thiazide diuretics can increase blood glucose levels (more insulin for diabetics)
  29. 29.  Heart failure most common and lethal disease in elderly  Fear of this condition may be the one reason why physicians overuse cardiac glycosides in this age group  Digoxin mostly used and clearence is mostly decreased in elderly and half life increased so following adverse reactions occur
  30. 30. ◦ Fatigue ◦ Loss of appetite, nausea, vomiting ◦ Visual disturbances ◦ Nightmares, nervousness ◦ Hallucinations ◦ Bradycardia, arrhythmias
  31. 31.  Treatment of arrhythmias in elderly is particularly challenging due to  lack of good hemodynamic reserves'  Frequency of electrolyte disturbance  High prevalence of coronary disease
  32. 32.  Following ADRS observed due to decreased clearance and increased half life of antiarrhythmics ◦ Confusion ◦ Slurred speech ◦ Light-headedness, seizures ◦ hypotension
  33. 33.  Age related changes contributes to incidence of infection in elderly patients  Reduction in host defense manifested in the increase in both serious infection and cancer  In the lungs age dependent decrease in the mucociliary clearance significantly increase in susceptibility of infection  In urinary tract,incidence of infections is greatly increased by urinary retention
  34. 34.  Since 1940, antimicrobial have contributed more to prolong the life because they can compensate to some extent for this deterioration in natural defenses  Because most antibiotics are excreted renal route so change in half life may occur so adverse reactions takes place
  35. 35.  Osteoarthritis most commonly present in elderly patients  NSAIDs and corticosteroids are mostly used  Corticosteroids are extremely useful in elderly who cannot tolerate full doses of NSAIDs however consistently cause increase in osteoporosis
  36. 36.  NSAIDs ◦ Prolong bleeding  Gastric discomfort, bleeding ◦ Increased risk of toxicity (with impaired renal function)
  37. 37.  Corticosteriods ◦ Sodium retention (may worsen HTN & CHF) ◦ Insomnia ◦ Psychotic behavior ◦ osteoporosis
  38. 38.  Disease is characterized by progressive impairment of memory and cognitive function, prevalence increases with age  Pathological changes includes increased deposits of amyloid beta peptide in cerebral cortex due to progressive loss of neurons especially cholinergic neurons and thinning of cortex  Many methods of treatment of Alzheimer`s disease has been explored
  39. 39.  Most attention has been focused on the cholinomimetics drugs because of evidence of loss of cholinergic neurons  Tacrine, donepezil, rivastigmine, and galantamine are used as these are cholinesterase inhibitors  ADRs include nausea, vomiting, and peripheral cholinomimetics effects  Memantine binds to NMDA and produce noncompetitive blockade and better tolerated and less toxic than cholinestrase inhibitors
  40. 40.  Glaucoma is most common in elderly but treatment is same as that for glaucoma of earlier onset  Age-related macular degeneration(AMD) is the most common cause of blindness in elderly patients  Two types 1.wet form 2.dry form  Cause of AMD is not known but smoking and oxidative stress has long been thought to play a role
  41. 41.  So antioxidants have been used to prevent or delay the onset of AMD  Oral formulations of vitamins C and E, beta- carotene, zinc oxide are available  Now laser phototherapy and antibiotics are used  Antibiotics bevacizumab, ranibizumab and pegabtanib are approved for AMD  these agents are injected into vitreous for local effect
  42. 42.  Balance between overprescribing and underprescribing ◦ Correct drug ◦ Correct dose ◦ Targets appropriate condition ◦ Is appropriate for the patient Avoid “a pill for every ill” Always consider non-pharmacologic therapy
  43. 43.  Polypharmacy  Multiple co-morbid conditions  Prior adverse drug event  Low body weight or body mass index  Age > 85 years  Estimated CrCl <50 mL/min
  44. 44.  Absorption may be  or   Drugs with similar effects can result additive effects  Drugs with opposite effects can antagonize each other  Drug metabolism may be inhibited or induced
  45. 45. Combination Risk ACE inhibitor + potassium Hyperkalemia ACE inhibitor + K sparing diuretic Hyperkalemia, hypotension Digoxin + antiarrhythmic Bradycardia, arrhythmia Digoxin + diuretic Antiarrhythmic + diuretic Electrolyte imbalance; arrhythmia Diuretic + diuretic Electrolyte imbalance; dehydration Benzodiazepine + antidepressant Benzodiazepine + antipsychotic Sedation; confusion; falls CCB/nitrate/vasodilator/diuretic Hypotension
  46. 46.  Obesity alters Vd of lipophilic drugs  Ascites alters Vd of hydrophilic drugs  Dementia may  sensitivity, induce paradoxical reactions to drugs with CNS or anticholinergic activity  Renal or hepatic impairment may impair metabolism and excretions of drugs  Drugs may exacerbate a medical condition
  47. 47. Combination Risk NSAIDs + CHF Thiazolidinediones + CHF Fluid retention; CHF exacerbation BPH + anticholinergics Urinary retention CCB + constipation Narcotics + constipation Anticholinergics + constipation Exacerbation of constipation Metformin + CHF Hypoxia; increased risk of lactic acidosis NSAIDs + gastropathy Increased ulcer and bleeding risk NSAIDs + HTN Fluid retention; decreased effectiveness of diuretics
  48. 48.  Avoid prescribing prior to diagnosis  Start with a low dose  Avoid starting 2 agents at the same time  Reach therapeutic dose before switching or adding agents  Consider non-pharmacologic agents
  49. 49.  Review medications regularly and each time a new medication started or dose is changed  Maintain accurate medication records (include vitamins, OTCs, and herbals)
  50. 50.  Suggest physician prescribe combination drugs or long-acting forms ◦ Fewer pills to remember  Suggest re-evaluation of medications periodically  Encourage client to use one pharmacy  New medications ◦ Good information ◦ Encourage follow up
  51. 51.  There are several practical obstacles to compliance that the prescriber must recognize ◦ Forgetfulness ◦ Prior experience ◦ Physical disabilities  Recommendations to improve compliance ◦ Take careful drug history ◦ Prescribe only for a specific and rational indication ◦ Define goal of drug therapy ◦ High index of suspicion regarding drug reactions and interactions ◦ Simplify drug regimen
  52. 52.  Avoid newer, more expensive medications that are not shown to be superior to less expensive generic alternatives  Simplify the regimen  Utilize pill organizers or drug calendars  Educate patient on medication purpose, benefits, safety, and potential ADEs
  53. 53.  Basic and Clinical Pharmacology by Bertram G. Katzung Susan B. Master