Outline the pharmacokinetic consequences of old age. Illustrate your answer with examples.
As the general population ages, and many elderly are admitted to intensive care units and/or encountered during intensive care ward consultations, this topic is highly relevant. Unfortunately candidate performance generally lacked sufficient depth and breadth in this area. Good answers were expected to mention changes in body compartments (eg total body water, lean body mass decrease, etc), consequences of changes in organ function (eg deteriorating glomerular filtration rate, reduced liver blood flow, etc), alterations in protein levels and binding, increased likelihood of drug interactions and the influence of disease states.
Syllabus: Generic Pharmacology III2d
References: Millers’ Anaesthesia Chp 19
The college answer, while highly critical of trainees, offers little in the way of explaining what precisely was expected from them. Nor are examples offered. One might imagine that a structured answer with examples might have attracted marks. The answer below is offered in the format of [mechanism] = [consequences](example) so as to satisfy the criteria of the answer. A detailed discussion of these issues can be found in the chapter on pharmacokinetics of old age.
Decreased dose response
Increased dose response
Jansen, Paul AF, and Jacobus RBJ Brouwers. "Clinical pharmacology in old persons." Scientifica 2012 (2012).
Turnheim, Klaus. "When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly." Experimental gerontology 38.8 (2003): 843-853.
Turnheim, Klaus. "Drug dosage in the elderly." Drugs & aging13.5 (1998): 357-379.
EVANS, MARK A., et al. "Gastric emptying rate in the elderly: implications for drug therapy." Journal of the American Geriatrics Society 29.5 (1
Russell, Tanya L., et al. "Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women." Pharmaceutical research 10.2 (1993): 187-196.
Merfeld, A. E., et al. "The effect of pH and concentration on α‐methyldopa absorption in man." Journal of pharmacy and pharmacology 38.11 (1986): 815-822.
Holt, Peter R. "Intestinal malabsorption in the elderly." Digestive Diseases 25.2 (2007): 144-150.
Bender, A. Douglas. "Effect of age on intestinal absorption: implications for drug absorption in the elderly." Journal of the American Geriatrics Society 16.12 (1968): 1331-1339.
Kaestli, Laure-Zoé, et al. "Use of transdermal drug formulations in the elderly." Drugs & aging 25.4 (2008): 269-280.
Holdsworth, Mark T., et al. "Transdermal fentanyl disposition in elderly subjects." Gerontology 40.1 (1994): 32-37.
Roskos, Kathleen V., Howard I. Maibach, and Richard H. Guy. "The effect of aging on percutaneous absorption in man." Journal of Pharmacokinetics and Pharmacodynamics 17.6 (1989): 617-630.
Klein, C., et al. "Transdermal clonidine therapy in elderly mild hypertensives: effects on blood pressure, plasma norepinephrine and fasting plasma glucose." Journal of hypertension. Supplement: official journal of the International Society of Hypertension 3.4 (1985): S81-4.
Kentala, Erkki, Timo Kaila, and Jussi Kanto. "Intramuscular atropine in elderly people: pharmacokinetic studies using the radioreceptor assay and some pharmacodynamic responses." Basic & Clinical Pharmacology & Toxicology 65.2 (1989): 110-112.
Divoll, Marcia, et al. "Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex." Anesthesia & Analgesia 62.1 (1983): 1-8.
Collart, P., et al. "Kinetic study of serum penicillin concentrations after single doses of benzathine and benethamine penicillins in young and old people." Sexually Transmitted Infections 56.6 (1980): 355-362.
Dube, A. H. "A comparison of serum concentrations produced by phenethicillin, penicillin V, and penicillin G after oral and intramuscular administration in geriatric patients." Antibiotics & Chemotherapy 11.10 (1961): 625-9.
GREENBLATT, DAVID J. "Reduced serum albumin concentration in the elderly: a report from the Boston Collaborative Drug Surveillance Program." Journal of the American Geriatrics Society 27.1 (1979): 20-22.
Routledge, PhA. "The plasma protein binding of basic drugs." British journal of clinical pharmacology 22.5 (1986): 499-506.
Le Couteur, David G., and Allan J. McLean. "The aging liver." Clinical pharmacokinetics 34.5 (1998): 359-373.
Mangoni, Arduino A., and Stephen HD Jackson. "Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications." British journal of clinical pharmacology 57.1 (2004): 6-14.
Toornvliet, Rolf, et al. "Effect of age on functional P‐glycoprotein in the blood‐brain barrier measured by use of (R)‐[11C] verapamil and positron emission tomography." Clinical Pharmacology & Therapeutics 79.6 (2006): 540-548.
Sun, Haiying, et al. "Drug efflux transporters in the CNS." Advanced drug delivery reviews 55.1 (2003): 83-105.