Geriatric pharmacology basic

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