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
Absorption Esophageal motility
Adults
Elderly
Gastric emptying time (half time, min)
Achlorhydria (incidence, %) Muscle mass and blood flow
47
5
123
26
ALTERED PHYSIOLOGIC VARIABLES IN OLDER PATIENTS
Physiologic Variable Distribution
Serum albumin Alpha-1 acid glycoprotein (mg/dL) Total body water (L/kg weight)
Adults
Elderly
4.7 28 .50
3.8 102 .47
36 45
Adipose tissue (% total body weight) Male 18
Female
33
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
122 1100
20 800 28
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-desmethyldiazepam
Clorazepate Prazepam Halazepam
N-methyloxazepam
Oxazepam
Hydroxyprazepam Lorazepam
Alprazolam
glucuronide
α –hydroxy-alprazolam
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
significant changes in absorption Increased adipose tissue changes distribution of fat soluble drugs Decreased cardiac output
on hepatic metabolism for most drugs Decreased renal excretion most significant
Little effect
No
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