Transcript PHARMACOLOGY AND THE ELDERLY

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
time, min)
47
123
Achlorhydria (incidence, %)
5
26
Muscle mass and blood flow

ALTERED PHYSIOLOGIC VARIABLES
IN OLDER PATIENTS
Physiologic Variable
Adults
Elderly
Distribution
Serum albumin
Alpha-1 acid glycoprotein (mg/dL)
Total body water (L/kg weight)
4.7
28
.50
Adipose tissue (% total body weight)
Male
18
Female
33
3.8
102
.47
36
45
ALTERED PHYSIOLOGIC VARIABLES
IN OLDER PATIENTS
Physiologic Variable
Adults
Older Adult
Metabolism
Liver weight (gm/kg body weight)
Hepatic blood flow (mL/min)
Antipyrine clearance (mL/hr/kg)
25
1400
47
20
800
28
122
1100
85
600
Elimination
Glomerular filtration rate
Renal blood flow (mL/min/1.73m2)

From Timiras, 1994
Diazepam Pharmacokinetics

Klotz et al., J. Clin. Invest., 1975
Metabolism of Benzodiazepines
Chlordiazepoxide
N-desmethylchlordiazepoxide
Demoxepam
Diazepam
N-methyloxazepam
Alprazolam
N-desmethyldiazepam
Oxazepam
glucuronide
α –hydroxy-alprazolam
Clorazepate
Prazepam
Halazepam
Hydroxyprazepam
Lorazepam
Plasma Half-Lives in Young and Old
Drug
Penicillin G
Tetracycline
Digoxin
Diazepam
Lidocaine
Chlordiazepoxide
Phenobarbital
Warfarin
Young (20-30)
20.7 min
3.5 hr
51 hr
20 hr
80.6 hr
8.9 hr
71 hr
37 hr
Elderly (65-80)
39.1 min
4.5 hr
73 hr
80 hr
139.6 hr
16.7 hr
107 hr
44 hr
Physiological Changes
 No
significant changes in absorption
 Increased adipose tissue changes distribution of fat
soluble drugs
 Decreased cardiac output
 Little
effect on hepatic metabolism for most drugs
 Decreased renal excretion most significant
Representative Drugs Showing Low Oral Availability
Due to Extensive First-Pass Hepatic Elimination
Alprenolol
 Amitriptyline
 Desipramine
 Dextropropxyphene
 Dihydroergotamine
 Diltiazem
 5-flurouracil
 Hydralazine
 Labetolol

Methylphenidate
 Metoprolol
 Morphine
 Nifedipine
 Nitroglycerin
 Pentazocine
 Propranolol
 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
 Benzodiazepines
 Beta-blockers
 Cimetidine
 Corticosteroids
 Digoxin
 Levodopa

Lithium
 NSAIDs
 Phenytoin
 Quinidine

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
