PHARMACOLOGY ANDTHE 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 4.7 3.8Alpha-1 acid glycoprotein (mg/dL) 28 102Total body water (L/kg weight) .50 .47

Adipose tissue (% total body weight)

Male 18 36Female 33 45

ALTERED PHYSIOLOGIC VARIABLESIN OLDER PATIENTS

Physiologic Variable Adults Older Adult

Metabolism

Liver weight (gm/kg body weight) 25 20Hepatic blood flow (mL/min) 1400 800Antipyrine clearance (mL/hr/kg) 47 28

EliminationGlomerular filtration rate 122 85Renal blood flow (mL/min/1.73m2) 1100 600

From Timiras, 1994

Diazepam Pharmacokinetics

Klotz et al., J. Clin. Invest., 1975

Chlordiazepoxide N-desmethylchlordiazepoxide

Demoxepam

N-desmethyldiazepam

Oxazepam

glucuronide

ClorazepatePrazepamHalazepam

Hydroxyprazepam

Lorazepam

Diazepam

N-methyloxazepam

Alprazolam

α –hydroxy-alprazolam

Metabolism of Benzodiazepines

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

Little effect on hepatic metabolism for most drugsDecreased 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

AnxietyAgitationConfusionDelirium Increased forgetfulnessHallucinationsSeizures

Other Drugs That May Cause Dementiaor Cognitive Impairment

Alcohol Benzodiazepines Beta-blockers Cimetidine Corticosteroids Digoxin Levodopa

Lithium NSAIDs Phenytoin Quinidine

Herbal Drug Use Today

Arch Intern Med. 2005

Copyright restrictions may apply.

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

Use of herbal products according to year of

interview and age of subject

Copyright restrictions may apply.

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

Weekly Prevalence of Use of Most Commonly Reported Herbal and Other Natural Dietary Supplements in 1998-1999 and 2002

According to Age Among Men*

Copyright restrictions may apply.

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

Weekly Prevalence of Use of Most Commonly Reported Herbal and Other Natural Supplements in 1998-1999 and

2002 According to Age Among Women*

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