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PHARMACOLOGY AND THE ELDERLY

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					PHARMACOLOGY AND
 THE OLDER PATIENT

     David J. Mokler, Ph.D.
 Department of Pharmacology
College of Osteopathic Medicine
  University of New England
              Learning Outcomes
 What are the physiologic changes that occur as we age
  that alter our response to drugs?
 What is the effect of these changes on the
  pharmacokinetics of commonly used drugs?
 What is anti-cholinergic syndrome?
 What are other classes of drugs that can cause cognitive
  impairment?
 What are the problems that are associated with the
  increased use of herbal medicines?
 What steps can we take to decrease the problems
  associated with polypharmacy?
   ALTERED PHYSIOLOGIC
VARIABLES IN OLDER PATIENTS
Physiologic Variable          Adults   Elderly
Absorption

Esophageal motility                        
Gastric emptying time (half       47      123
time, min)
Achlorhydria (incidence, %)       5        26

Muscle mass and blood flow                 
      ALTERED PHYSIOLOGIC
   VARIABLES IN OLDER PATIENTS
Physiologic Variable                Adults        Elderly

Distribution
Serum albumin                               4.7       3.8
Alpha-1 acid glycoprotein (mg/dL)         28          102
Total body water (L/kg weight)            .50         .47
   Adipose tissue (% total body weight)
   Male                                   18           36
   Female                                 33           45
       ALTERED PHYSIOLOGIC VARIABLES
             IN OLDER PATIENTS

Physiologic Variable                  Adults   Older Adult

Metabolism
Liver weight (gm/kg body weight)         25        20
Hepatic blood flow (mL/min)             1400       800
Antipyrine clearance (mL/hr/kg)          47        28
Elimination
   Glomerular filtration rate           122        85
   Renal blood flow (mL/min/1.73m2)     1100       600
   From Timiras, 1994
        Diazepam Pharmacokinetics




   Klotz et al., J. Clin. Invest., 1975
     Metabolism of Benzodiazepines
Chlordiazepoxide           N-desmethylchlordiazepoxide


                                Demoxepam


                                                     Clorazepate
      Diazepam             N-desmethyldiazepam       Prazepam
                                                     Halazepam

  N-methyloxazepam               Oxazepam
                                              Hydroxyprazepam


Alprazolam                      glucuronide          Lorazepam

             α –hydroxy-alprazolam
  Plasma Half-Lives in Young and Old
Drug               Young (20-30)   Elderly (65-80)
Penicillin G       20.7 min        39.1 min
Tetracycline       3.5 hr          4.5 hr
Digoxin            51 hr           73 hr
Diazepam           20 hr           80 hr
Lidocaine          80.6 hr         139.6 hr
Chlordiazepoxide   8.9 hr          16.7 hr
Phenobarbital      71 hr           107 hr
Warfarin           37 hr           44 hr
             Physiological Changes
 No  significant changes in absorption
 Increased adipose tissue changes distribution of fat
  soluble drugs
 Decreased cardiac output
         effect on hepatic metabolism for most drugs
   Little
   Decreased renal excretion most significant
Representative Drugs Showing Low Oral Availability
  Due to Extensive First-Pass Hepatic Elimination
   Alprenolol           Methylphenidate
   Amitriptyline        Metoprolol
   Desipramine          Morphine
   Dextropropxyphene
                         Nifedipine
   Dihydroergotamine
                         Nitroglycerin
   Diltiazem
                         Pentazocine
   5-flurouracil
                         Propranolol
   Hydralazine
   Labetolol            Verapamil
DRUGS WITH ANTI-CHOLINERGIC
        PROPERTIES
 Anti-psychotics: Chlorpromazine
 Anti-depressants: Amitriptyline, doxepin
 Anti-arrhythmics: Quinidine, disopyramide
 Anti-parkinson drugs: Benztropine, trihexyphenidyl
 Anti-spasmodics: Atropine
 Anti-histamine: Diphenhydramine, chlorpheneramine
 Proprietary sleep aids, cold medications
Anti-Cholinergic Syndrome
   Systemic
     Tachycardia
     Warm, dry, flushed skin
     Decreased secretions
     Decreased bowel motility (constipation)
     Urinary retention
     Mydriasis, blurred vision
     Hyper-pyrexia
     Cardiac conduction problems
Anti-Cholinergic Syndrome
    Neuropsychiatric
      Anxiety
      Agitation
      Confusion
      Delirium
      Increased forgetfulness
      Hallucinations
      Seizures
Other Drugs That May Cause Dementia
       or Cognitive Impairment
  Alcohol            Lithium
  Benzodiazepines    NSAIDs

  Beta-blockers      Phenytoin

  Cimetidine         Quinidine

  Corticosteroids
  Digoxin
  Levodopa
               Arch Intern Med. 2005

Herbal Drug Use Today
   Use of herbal products
    according to year of
interview and age of subject




                                    Kelly, J. P. et al. Arch Intern Med 2005;165:281-286.



Copyright restrictions may apply.
                        Weekly Prevalence of Use of Most Commonly Reported Herbal
                        and Other Natural Dietary Supplements in 1998-1999 and 2002
                                      According to Age Among Men*




                    Kelly, J. P. et al. Arch Intern Med 2005;165:281-286.




Copyright restrictions may apply.
                                    Weekly Prevalence of Use of Most Commonly Reported
                                    Herbal and Other Natural Supplements in 1998-1999 and
                                            2002 According to Age Among Women*




                Kelly, J. P. et al. Arch Intern Med 2005;165:281-286.




Copyright restrictions may apply.
Herbal Therapies
Herbal Therapies
A stepwise approach to polypharmacy
  Disclose all medications being used, including OTC,
   herbals and supplements
  Identify medications by generic name and drug class
  Identify the clinical indication for each drug
  Know the side effect profile for each drug
  Identify risk factors for adverse drug reactions
  Eliminate medication with no therapeutic benefit
  Eliminate medication with no clinical indication
  Substitute safer medication
  Avoid treating adverse drug reactions with a drug
  Use a single drug with infrequent dosing

				
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