Geriatric pharmacology - Introduction

1. Geriatric Pharmacology
Dr. S. Parasuraman M.Pharm., Ph.D.,
Senior Lecturer, Faculty of Pharmacy,
AIMST University,
Bedong 08100, Malaysia.

2. Pharmacokinetics in the Elderly
• Drug absorption:

3. Pharmacokinetics in the Elderly
• Drug absorption affected by:
– Increase in Gastric pH
– Reduction of gastrointestinal motility
– Reduction in blood flow
– Gastrointestinal flora/ Decrease absorption surface
in the gastrointestinal tract
– Gastric enzymes

4. Pharmacokinetics in the Elderly
• Drug distribution affected by :
– Blood flow
– Plasma protein binding
– Physico-chemical properties of the drug
– Reduction in total body water

5. Pharmacokinetics in the Elderly
• Drug metabolism affected by:
– Hepatic metabolism
– Genetic influences on liver enzymes
• Cytochrome P450 enzymes
• Fast metabolisers vs. Slow metabolisers
– Liver metabolism is also influenced by smoking,
liver disease, alcohol nutritional status and
influence of other drugs

6. Pharmacokinetics in the Elderly
• Drug elimination affected by:
– Aging causes reduced renal function
– 30-35% reduction in glomerular filtration and renal
blood flow

7. Pharmacokinetics in the Elderly
Drug absorption
• Increase in Gastric pH:
– Age dependent decreases in bowel surface area, slowing
gastric emptying and increase in gastric pH changes the drug
absorption. Age related increases in gastric pH decreases the
absorption and increases the risk of development of adverse
events. Example: Altered absorption is early release of
enteric-coated dosage forms with increased gastric pH.

8. • Reduction of gastrointestinal motility:
– Motility disorders associated with non-erosive or atypical
gastroesophageal reflux disease (atypical GERD), gastroparesis
and small intestine dysmotility are alters the drug absorption.
– Poorly absorbed drugs alter the rate of absorption and
bioavailability which likely to be by changes in gastrointestinal
motility. [Hebbard, 1995]
Cont.,
Pharmacokinetics in the Elderly
Drug absorption

9. • Reduction of gastrointestinal motility:
– In patients with gastrointestinal motility disorders, drugs
administered in a controlled release formulation, or those
with poor bioavailability, are most likely to have a poorly
predictable therapeutic effect.
– Care should be taken to ensure that the formulation of the
drug, its timing of administration in relation to meals and the
use of coadministered drugs optimise, or at least ensure
consistent absorption. [Hebbard, 1995]
Pharmacokinetics in the Elderly
Drug absorption

10. • Reduction in blood flow:
– Normal blood flow or increased in splanchnic blood flow may
help drug to achieve higher plasma concentration. In elderly,
subject may have reduced blood enterohepatic circulation
which may reduce the absorption rate and interfere with Cmax.
The drugs like propranolol, chloramphenicol and lithium
carbonate may have maximum absorption with increased
splanchnic blood flow.
Pharmacokinetics in the Elderly
Drug absorption

11. • Gastrointestinal flora/ Decrease absorption
surface in the gastrointestinal tract:
– The intestine has a surface rich in microvilli and it has a
surface area about 1000-fold that of the stomach thus,
absorption of the drug across the intestine is more efficient.
Area of absorbing surface is plays important role in drug
which administered through oral route.
Pharmacokinetics in the Elderly
Drug absorption

12. • Gastrointestinal flora/ Decrease absorption
surface in the gastrointestinal tract:
– The lung and gastrointestinal track has huge surface area and
helps in absorption of drugs. The stomach and intestinal flora
(villi) is end up with a total surface area of around 200 m2. In
elderly, subject may have poor gastrointestinal ability which
reduces the drug absorption rate.
Pharmacokinetics in the Elderly
Drug absorption

13. • Gastrointestinal flora/ Decrease absorption
surface in the gastrointestinal tract:
– Area of absorptive surface affects oral as well as other
routes. Most of the drugs are given orally because of the
large area of absorptive surface, so that greater
absorption occurs. Intestinal resection decreases the
surface area leading to a decreased absorption. Similarly,
when the topically acting drugs are applied on a large
surface area, they are better absorbed.
Pharmacokinetics in the Elderly
Drug absorption

14. • Gastric enzymes:
– Disintegration and dissolution rate may affect the drug
absorption. In elderly, secretion of gastric enzyme may be get
reduce which affects the drug disintegration time and
dissolution rate. The delay in disintegration time and
dissolution rate may increase the time of drug absorption and
delays the pharmacological actions of drug after oral drug
administration.
Pharmacokinetics in the Elderly
Drug absorption

15. Pharmacodynamics in the Elderly
• Some drugs can have varying effects in the
elderly due to
– Changes in the number of receptors
– Changes in the binding affinity
– Deficits in homeostatic mechanisms
– Pharmacodynamic interactions

16. • Otherwise called as drug–drug interactions.
• Pharmacodynamic interactions occur when one drug
changes the response to another drug. Drug–drug
interactions play an important role in patient safety.
The risk of drug–drug interactions increases with age
and the number of drugs used. Most often drug–drug
interactions are preventable.
Pharmacodynamics in the Elderly
Pharmacodynamic interactions

17. • Examples of common drug–drug interactions:
Pharmacodynamics in the Elderly
Pharmacodynamic interactions

18. • The inter-individual variability in susceptibility to drugs is at
least partly explained by differences in multi-morbidity.
• Diseases that affect the kidneys make the elderly patient
more susceptible to ADR due to reduction in renal
elimination.
• Liver diseases as well as cardiac diseases that affect hepatic
blood flow may affect drug metabolism. In the same way,
diseases that affect other organ systems may make elderly
patients even more susceptible to drugs.
Pharmacodynamics in the Elderly
Drug–disease interactions

19. • Examples of common drug–drug interactions:
Pharmacodynamics in the Elderly
Drug–disease interactions

20. • Drug–food interaction adds variability to effects and
adverse effects of drugs.
• For example, warfarin is known for its drug–food
interactions. Warfarin has a narrow therapeutic interval
and food with a high K-vitamin content counteract the
effects of warfarin.
Pharmacodynamics in the Elderly
Drug–food interactions

21. • Other examples are grapefruit juice that inhibits the
metabolism of cyclosporine and non-selective monoamine
oxidase (MAO) inhibitor with food rich in tyramine. Some
fermented and stored products (e.g. some cheese,
sausages, red wine) contain tyramine that is metabolised to
noradrenaline, which in conjunction with MAO inhibitors
may block MAO and cause a hypertensive crisis. Seligiline
and moclobemide are examples of MAO inhibitors.
Pharmacodynamics in the Elderly
Drug–food interactions

22. • Duration of illness
• Medical co-morbidities
• Loss of effect with drugs
• Limited dosing flexibility
Limitations in treating the Elderly
Minimizing adverse effects
• Possibly use non-pharmacological approach or physical
therapy
• Lowest effective and feasible dose
• Avoid multi-drug regiment wherever possible and reduce
number of pills
• Regular interventions
• Frequent auditing of prescriptions.
• Making sure that the care-taker understanding the
medication and disease status

23. References
• Hebbard GS, Sun WM, Bochner F, Horowitz M.
Pharmacokinetic considerations in gastrointestinal motor
disorders. Clin Pharmacokinet. 1995;28(1):41-66.
• Midlöv P. Pharmacokinetics and pharmacodynamics in the
elderly. A Elderly Medicine 2013;1(1):1-5.
• Brunton L, Knollman B, Hilal-Dandan R. Goodman and
Gilman's The Pharmacological Basis of Therapeutics, 12th Ed,
New York: McGraw-Hill Education, 2011.
• Walker R, Whittlesea C. Clinical Pharmacy and Therapeutics,
5th Ed, London: Churchill Livingstone - imprint of Elsevier,
2012.

24. Thank you