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Slide 1                    © 2001 By Default!




          Pharmacologic
          Considerations
            Geriatrics
Slide 2                                               © 2001 By Default!


                        Introduction
         In the US, the elderly (>65y/o) constitute ~12% of
          the total population, but account for almost 30% of
          total drug expenditure

         Age-related physiologic changes make the elderly
          susceptible to adverse effects

         Understanding the influence these changes have
          on the pharmacokinetics and pharmacodynamics of
          the elderly is essential to prevent harm
Slide 3                                                       © 2001 By Default!

              Physiologic Changes of Aging
                  Affecting Absorption
     Physiologic change
          –   Decreased gastric acidity
          –   Decreased gastrointestinal blood flow
          –   Delayed grastric 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
     Special considerations
          – Antacids decrease absorption of acidic drugs: digitalis,
            phenytoin, tetracycline
          – Anticholinergics: Slow GI motility and absorption rate
Slide 4                                                       © 2001 By Default!

           Physiologic Changes of Aging
              Affecting Distribution
     Decreased Total body water
          – Decreased Volume Distribution
          – Increased Plasma Conc. of water soluble drugs
          – Lower doses are required: Lithium, digoxin, ethanol, etc
     Decreased Lean body mass and Increased body fat
          – 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
Slide 5                                                     © 2001 By Default!


                          Metabolism
         Determined
          – Primarily by hepatic function and blood flow
          – Capacity of the liver to metabolize drugs does not appear
            to decline consistently with age for all drugs
Slide 6                                                     © 2001 By Default!


                           Elimination
         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
Slide 7                                                     © 2001 By Default!

           Physiologic Changes of Aging
               Affecting Elimination
     Physiologic change
          – Decreased GFR
          – Decreased renal blood flow
          – Decreased renal mass
     General clinical effect
          – Decreased clearance, Increased (t½) of renally eliminated
            drugs
Slide 8                                               © 2001 By Default!


                   Pharmacodynamics
         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
Slide 9                                                      © 2001 By Default!

            Major Drug Groups Requiring
                     Monitoring
     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
Slide 10                                              © 2001 By Default!

       Major Reasons for Adverse Drug
           Reactions in the Elderly
     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
Slide 11                                                 © 2001 By Default!


                           Compliance
      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

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Geriatrics and pharmacology

  • 1. Slide 1 © 2001 By Default! Pharmacologic Considerations Geriatrics
  • 2. Slide 2 © 2001 By Default! Introduction  In the US, the elderly (>65y/o) constitute ~12% of the total population, but account for almost 30% of total drug expenditure  Age-related physiologic changes make the elderly susceptible to adverse effects  Understanding the influence these changes have on the pharmacokinetics and pharmacodynamics of the elderly is essential to prevent harm
  • 3. Slide 3 © 2001 By Default! Physiologic Changes of Aging Affecting Absorption  Physiologic change – Decreased gastric acidity – Decreased gastrointestinal blood flow – Delayed grastric 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  Special considerations – Antacids decrease absorption of acidic drugs: digitalis, phenytoin, tetracycline – Anticholinergics: Slow GI motility and absorption rate
  • 4. Slide 4 © 2001 By Default! Physiologic Changes of Aging Affecting Distribution  Decreased Total body water – Decreased Volume Distribution – Increased Plasma Conc. of water soluble drugs – Lower doses are required: Lithium, digoxin, ethanol, etc  Decreased Lean body mass and Increased body fat – 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
  • 5. Slide 5 © 2001 By Default! Metabolism  Determined – Primarily by hepatic function and blood flow – Capacity of the liver to metabolize drugs does not appear to decline consistently with age for all drugs
  • 6. Slide 6 © 2001 By Default! Elimination  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
  • 7. Slide 7 © 2001 By Default! Physiologic Changes of Aging Affecting Elimination  Physiologic change – Decreased GFR – Decreased renal blood flow – Decreased renal mass  General clinical effect – Decreased clearance, Increased (t½) of renally eliminated drugs
  • 8. Slide 8 © 2001 By Default! Pharmacodynamics  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
  • 9. Slide 9 © 2001 By Default! Major Drug Groups Requiring Monitoring  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
  • 10. Slide 10 © 2001 By Default! Major Reasons for Adverse Drug Reactions in the Elderly  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
  • 11. Slide 11 © 2001 By Default! Compliance  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