- Physiological changes that occur with aging can impact drug pharmacokinetics and pharmacodynamics in older adults, resulting in increased drug sensitivity and decreased drug clearance. Factors like reduced liver and kidney function as well as changes in body composition can affect absorption, distribution, metabolism and elimination of medications. - Prescribing for older adults requires lower starting doses, longer dosing intervals, and careful monitoring due to higher risks of adverse drug reactions, drug-drug interactions, and non-adherence related to polypharmacy or complex regimens. Guidelines like the Beers criteria can help minimize inappropriate prescribing for geriatric patients.

1. GERIATRIC
PHARMACOLOGY

2. Ageing
■ Time associated events that occur during the life span
of an organism
■ Deteriorative changes with time during post
maturational life that underlie an increasing
vulnerability to challenges, thereby decreasing the
ability of the organism to survive

3. Physiological changes
■ Function capacity of major organ systems
■ Body composition
■ Nutritional state
■ Insults during lifetime

4. Learning objectives
■ effect of age on PK and PD
■ adverse drug reactions and ways to mitigate them
■ principles of drug prescribing for older patients

5. Pharmacokinetics
■ Absorption
■ Distribution
■ Metabolism
■ Elimination

6. Absorption
Oral absorption:
Gastric acid – gastric pH
Gastric motility
gastric emptying time
peristalsis
gastric blood flow

7. Absorption
■ Bioavailability

8. Absorption
Absorption
 blood supply to
 absorptive surface area
 GIT motility

9. It depends on two main factors :
1.Plasma protein binding
2.Body composition : % of Total Body Water
% of Lean body mass
% of Fat stores in the body
Distribution

10. Variable Aging Effect Vd Effect Examples
Body water 60 vs 50  Vd for hydrophilic
drugs
lithium, Digoxin,
Ethanol, Gentamicin,
Phenytoin,
theophylline
Lean body mass 20 vs 12  Vd for for drugs that
bind to muscle
digoxin
Body fat 26-30 vs 38-45 (W)
18-20 vs 36-38 (M)
 Vd for lipophilic
drugs
 Parenteral loading
dose by 10 to 20%
diazepam, trazodone,
Paracetamol,
Oxazepam, Prazosin ,
Salicylates, Thiopental
Contd.

11. Plasma
albumin
Concentration
decreases
Unbound fraction
of drugs
like:Phenytoin,,
Diazepam
Alpha 1-acid
glycoprotein
Concentration
increases Unbound fraction of
Lidocaine
decreases by 40%.
Contd.

12. Metabolism

13. Aging Effects on Hepatic
Metabolism
■ Decrease in phase-1 metabolism and increased
terminal half life has been reported
■ Phase2 reactions appear to be generally spared
from any adverse effect of aging

14. ■ Age associated reduction in hepatic blood
flow can reduce the clearance of high
hepatic extraction ratio drugs

16. Concepts in Drug Elimination
■ Half-life
– time for plasma concentration of drug to decrease
by 50% (expressed in hours)
■ Clearance
– volume of plasma from which the drug is removed
per unit of time (mL/min or L/hr)
■ Decreased elimination  drug accumulation and
toxicity

17. Effects of Aging on the Kidney
■ Decrease in renal mass
■ Decrease in number and size of nephrons
■ Decrease in tubular secretion
■ Decrease in renal blood flow
Collectively causes decrease in drug clearance
Examples- atenolol,
H2 blockers,
digoxin ,

18. Estimating GFR in the Elderly
■ Creatinine clearance (CrCl) is used to estimate glomerular
filtration rate
■ Serum creatinine - normal range
–  lean body mass  lower creatinine production
–  glomerular filtration rate

19. Determining Creatinine Clearance
■ Estimate
– Cockroft Gault equation
(BW in kg) x (140-age)
----------------------------------- x (0.85 for
females)
72 x (Sr cr in mg/dL)

20. Limitations in Estimating CrCl
■ Not all persons experience significant decline in renal
function
24 hour creatinine clearance determination

21. Pharmacodynamics

22. CNS
Older patient are more sensitive to CNS
depressant action
PK effect
■ Benzodizepine drugs- diazepam, flurazepam
PD effect
■ Opioid drugs- fentanyl, alfentanil.
■ Anaesthetics- propofol

23. ANS
Aging effect
■ Decreased vagal tone
■ Impaired baroreceptor function
■ Orthostatic hypotension e.g. TCA, Neuroleptics.
■ Impaired thermoregulation e.g. anticholinergic drugs
(TCA,Neuroleptics causes hyperthermia)

24. CVS
AGING EFFECT
■ Low exercise tolerance
■ Deceased vascular elasticity
■ Low renin state

25. PD effect
■ Decreased sensitivity of beta receptor- agonist as well
as antagonist
No. of receptor actively coupled to adenylate cyclase
decreases with age.
■ Alpha blocker and calcium channel blocker –
exaggeration of hypotensive response
■ ACE inhibitor – less effective

26. Summary
■ PK and PD changes generally result in decreased clearance
and increased sensitivity to medications in older adults
■ Use of lower doses, longer intervals, slower titration are
helpful in decreasing the risk of drug intolerance and
toxicity
■ Careful monitoring is necessary to ensure successful
outcomes

27. ADRs
■ Greater than 95% of ADRs
in the elderly are considered
predictable and approximately
50% are considered preventable

28. Factors predisposing ADRs in
elderly
1. Patient related:
• Non- adherence: cognitive impairment, restricted movements,
economical problems, suicidal tendencies
• OTC Drugs: analgesics, sleep-pills
• OTC may contain “hidden drugs” e.g. Antihistaminic
• More than one disease

29. Contd.
1. Doctor-related
■ Unawareness:
■ Other drugs prescribed
■ PK & PD peculiarities in elderly
■ Drug interactions
– Complicated regimens
– Polypharmacy

31. Drug Related Problems
They can be:
 Underuse
 Overuse -polypharmacy
 Inappropriate prescribing
 Non-adherence to medication

32. Underuse
■ Omission of drug therapy that is indicated for the treatment or
prevention of a disease.
■ One study found that 55 % (out of 236 ) of elderly patients had
one or more necessary drug omitted.1
■ Eg. Underuse of Opioid analgesics in chronic painful conditions
like cancer

33. Overuse
Polypharmacy
■ 9 drugs/day or 12 doses/day.
■ Dietary supplements, vitamins, minerals.
■ Average of 5 med in hospitalized pts.

34. Non-adherence to medication
Reasons:
■ Multiple drugs
■ Multiple daily dosages
■ Frequently changing drug regimens
■ Cost
■ ADRs
■ Dependence on others
■ Progressively diminishing cognition, vision, dexterity,
mobility.
■ Social factors: loneliness, economical stress, loss of
spouse, social and familial neglect
■ Intentional/ intelligent non-adherence.

35. Preventing Polypharmacy
■ Review medications regularly at each time a new medication started or dose is
changed
■ Maintain accurate medication records (include vitamins, OTCs, and herbals)
■ Maintain pill boxes

36. Beers criteria
■ Mark H Beers, 1954-Feb 28, 2009
■ Came up with Beer’s list in 1991 (revised in 2003, 2008,2012,2015)
■ Specifies several groups of medications that can cause harm in elderly patients
■ Useful in the choice of the ‘first line drug’

37. Enhancing Medication Adherence
■ Avoid newer, more expensive medications
■ FDCs, Modified release preparations.
■ Simplify the regimen
■ Educate patient -medication purpose, benefits,
safety, and potential ADRs

38. Principles of Prescribing in the
Elderly
■ Avoid prescribing prior to diagnosis
■ Start with a low dose and titrate slowly
■ Reach therapeutic dose before switching or adding agents

39. Conclusions
■ Medication misuse in the elderly is a common and serious
problem.
■ Recognizing age-related changes in pharmacodynamics and
pharmacokinetics will contribute to better prescribing
practices for geriatric patients.
■ Final aim should be tailor make regimens as per the
individual.
■ Promoting clinical research in the elderly to better
extrapolate the findings.

40. REFERENCES
■ Katzung
■ Sougata Sarkar
■ M Tate, M AcGrane. Geriatyic Pharmacology. An update. Anes
■ Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is
polypharmacy? A systematic review of definitions. BMC Geriatr.
2017 Oct 10;17(1):230.
■ Hosseini SR, Zabihi A, Jafarian Amiri SR, Bijani A. Polypharmacy
among the Elderly. J Midlife Health. 2018 Apr- Jun;9(2):97-103.

41. THE END