PHARMACOLOGY RELATED TO GERIATRIC PATIENTS

1. IMMUNOPHARMACOLOGY
TOPIC:SPECIAL ASPECTS OF GERIATRICS
PHARMACOLOGU
BY:
DR. SABA AHMED
M PHIL PHARMACOLOGY
UOS

2.  20% of hospitalizations for those >65 are due
to medications they’re taking

3.  Alzheimer`s disease
 Parkinsonism
 Stroke
 Vascular dementia
 Visual impairment specially cataracts and macular
degeneration
 Atherosclerosis
 Arthritis
 Heart failure
 Fractures
 Cancer
 Diabetes
 Heart failure

4.  Physiologic change
◦ Decreased gastric acidity
◦ Decreased gastrointestinal blood flow
◦ Delayed gastric emptying
◦ Slowed intestinal transit time
 General clinical effect
◦ None on passive diffusion or bioavailability for most drugs
◦ Decreased active transport: Decreased bioavailability for
some drugs
◦ Decreased first-pass effect: Increased bioavailability for
some drugs

5.  Decreased Total body water
◦ Increased Plasma Conc. of water soluble drugs
◦ Lower doses are required: Lithium, digoxin, ethanol, etc
 Decreased Lean body mass
◦ Increased Volume Distribution, Longer (t½) of water soluble
drugs
◦ Accumulation into fat of lipid soluble drugs: Benzos, etc
 Decreased Serum Albumin
◦ Increased unbound fraction of highly protein bound drugs
◦ Binds acidic drugs: warfarin, phenytoin, digitalis, etc
 Decreased Alpha1 Acid glycoprotein
◦ Increased unbound fraction of highly protein bound drugs
◦ -Binds basic drugs: lidocaine and propranolol, etc

6.  Difficult to predict, depends on
General health & nutritional status
 Use of alcohol, medications
Long term exposure to environmental toxins/pollutants
 Aging causes decreased liver mass/ hepatic blood
flow
Delayed/reduced metabolism of drugs
Higher plasma levels
Greatest changes in phase 1 reaction those carry out
microsomal p450 enzyme system
Decline in liver ability to recover from injury
 Lower serum protein levels
Loss of protein binding
 Idiosyncratic reactions

7.  Metabolic clearance of drugs by the liver may
be reduced due to:
◦ decreased hepatic blood flow
◦ decreased liver size and mass
 Examples: morphine, meperidine, metoprolol,
propranolol, verapamil, amitryptyline,
nortriptyline

8.  Determined
◦ Primarily by renal function
◦ Declines with age and is worsened by co-morbidities
◦ Decline is not reflected in an equivalent rise in
serum creatinine since creatinine production is
reduced due to lower muscle mass

9.  Physiologic change
◦ Decreased GFR
◦ Decreased renal blood flow
◦ Decreased renal mass
 General clinical effect
◦ Decreased clearance, Increased (t½) of renally
eliminated drugs

10.  Creatinine clearance (CrCl) is used to
estimate glomerular rate
 Serum creatinine alone not accurate in the
elderly
◦  lean body mass  lower creatinine production
◦  glomerular filtration rate
 Serum creatinine stays in normal range,
masking change in creatinine clearance

11.  Measure
◦ Time consuming
◦ Requires 24 hr urine collection
 Estimate
◦ Cockroft Gault equation
(IBW in kg) x (140-age)
------------------------------ x (0.85 for
females)
72 x (Scr in mg/dL)

12.  Pharmacodynamic changes in the elderly have
been less extensively studied
 Evidence of enhanced end-organ
responsiveness or “sensitivity” to medications
with aging
 Enhanced “sensitivity” may be due
◦ Changes in receptor affinity
◦ Changes in receptor number
◦ Post-receptor alteration
◦ Age-related impairment of homeostatic mechanisms
Example: decreased baroreceptor reflexes

13.  Age-related changes:
◦  sensitivity to sedation and psychomotor
impairment with benzodiazepines
◦  level and duration of pain relief with narcotic
agents
◦  drowsiness with alcohol
◦  sensitivity to anti-cholinergic agents
◦  cardiac sensitivity to digoxin

14.  Cognitive changes associated with vascular
and other pathology
 Economic stresses with greatly associated
with reduced income or due increased
expenses due to illness
 Loss of spouse

15.  Positive relationship between number of drugs
taken and incidence
 Overall incidence is estimated to be at least twice
that in the younger population
 Prescribing errors
◦ Polypharmacy
◦ Drug interactions with other prescriptions
◦ Unawareness of age related physiologic changes
 Drug usage errors
◦ “Hidden ingredients”: OTCs

16. Factors contributing to adverse drug reactions
in elderly patients
Polypharmacy
How many prescription medications are too many? >4 or >6
Many elderly people receive 12 medications per day
Heart, kidney, liver,
thyroid

17.  Economic factors
◦ May have to choose between food and medications
 OTCs instead of expensive doctor visits
 Use of outdated medications
 Use of home remedies
 Share medications
 Nutritional status may affect how body metabolizes
medications

18.  Concurrent use of multiple medications
◦ >65 = 12% of population
◦ Consume 30% of all prescription drugs [average
person takes 4-5 prescription meds]
◦ Consume 40% of OTCs
 Excessive use of drugs
 Overdose of a drug

19.  Risks of problems:
◦ Medication errors
 Wrong drug, time, route
◦ Adverse effects from each drug
 Polypharmacy primary reason for adverse reactions
◦ Adverse interactions between drugs

20.  CNS drugs
◦ Sedative-hypnotics: Benzodiazepines and barbiturates
◦ Analgesics: Opioids
◦ Antipsychotic, antidepressants: Haloperidol, lithium, TCAs
 Cardiovascular drugs
◦ Antihypertensives: Thiazides, beta-blockers
 Antiarrhythmic drugs
◦ Quinidine and procainamide:  clearance and  (t½)
 Antimicrobial drugs
◦ Beta-lactams and aminoglycosides:  clearance
 Anti-inflammatory drugs
◦ NSAIDs: GI bleed and irritation

21. Half life of many drugs benzodiazepine and barbiturates
increases 50-150% between age 30 and 70
Age related decline in renal and liver function both
contribute to to the reduction in elimination of these
compounds .
Lorazepam and oxazepam may be less affected by these
change.
It is generally believed that the elderly vary more in their
sensitivity to these sedatives on PD basis as well.
Adverse reactions like Ataxia and motor impairment
mostly present

22.  Elderly are often markedly more sensitive to
the respiratory effect of these agents because
of age related changes in respiratory function
like airways and tissues become less elastic .

23.  Narcotic analgesics
◦ Respiratory depression
◦ Constipation
◦ Urinary retention
◦ Hypotension,
◦ dizzines
◦ confusion

24.  Phenothiazines and Heloperidol have been
heavily used in the management of variety of
psychiatric diseases in elderly .
 Useful in treatments of some symptoms
associated with delirium, dementia, agitation,
combativeness however their use is not
satisfactory in geriatrics conditions.
 Much of these improvements are simply reflect
the sedative effects
 Phenothiazines often induce orhtostatic
hypotension because of their a-adrenergic
blocking effects.

25.  Antipsychotics
◦ Jaundice
◦ Extrapyramidal symptoms
◦ Sedation, dizziness (can lead to falls)
◦ Orthostatic hypotension
◦ Scaling skin on exposure to sunlight
(phenothiazines)

26.  Tricyclic antidepressants
◦ Dry mouth
◦ Constipation
◦ Blurred vision
◦ Postural hypotension
◦ Dizziness
◦ Tachycardia
◦ Urinary retention

27.  Antihypertensive drugs
 Systolic blood pressure increases with age in western
countries and in most culture in which salt intake is high
 Drugs used for it are Thiazides ,calcium channel blocker ,beta
blockers etc
 ADRS related to these drugs
◦ Dizziness and falls
◦ Orthostatic hypotension

28.  Diuretics
◦ Fluid/electrolyte disorders
◦ Dehydration
◦ Hypotension
◦ Thiazide diuretics can increase blood glucose levels
(more insulin for diabetics)

29.  Heart failure most common and lethal disease
in elderly
 Fear of this condition may be the one reason
why physicians overuse cardiac glycosides in
this age group
 Digoxin mostly used and clearence is mostly
decreased in elderly and half life increased so
following adverse reactions occur

30. ◦ Fatigue
◦ Loss of appetite, nausea, vomiting
◦ Visual disturbances
◦ Nightmares, nervousness
◦ Hallucinations
◦ Bradycardia, arrhythmias

31.  Treatment of arrhythmias in elderly is
particularly challenging due to
 lack of good hemodynamic reserves'
 Frequency of electrolyte disturbance
 High prevalence of coronary disease

32.  Following ADRS observed due to decreased
clearance and increased half life of
antiarrhythmics
◦ Confusion
◦ Slurred speech
◦ Light-headedness, seizures
◦ hypotension

33.  Age related changes contributes to incidence
of infection in elderly patients
 Reduction in host defense manifested in the
increase in both serious infection and cancer
 In the lungs age dependent decrease in the
mucociliary clearance significantly increase in
susceptibility of infection
 In urinary tract,incidence of infections is
greatly increased by urinary retention

34.  Since 1940, antimicrobial have contributed
more to prolong the life because they can
compensate to some extent for this
deterioration in natural defenses
 Because most antibiotics are excreted renal
route so change in half life may occur so
adverse reactions takes place

35.  Osteoarthritis most commonly present in
elderly patients
 NSAIDs and corticosteroids are mostly used
 Corticosteroids are extremely useful in
elderly who cannot tolerate full doses of
NSAIDs however consistently cause increase
in osteoporosis

36.  NSAIDs
◦ Prolong bleeding
 Gastric discomfort, bleeding
◦ Increased risk of toxicity (with impaired renal
function)

37.  Corticosteriods
◦ Sodium retention (may worsen HTN & CHF)
◦ Insomnia
◦ Psychotic behavior
◦ osteoporosis

38.  Disease is characterized by progressive
impairment of memory and cognitive
function, prevalence increases with age
 Pathological changes includes increased
deposits of amyloid beta peptide in cerebral
cortex due to progressive loss of neurons
especially cholinergic neurons and thinning of
cortex
 Many methods of treatment of Alzheimer`s
disease has been explored

39.  Most attention has been focused on the
cholinomimetics drugs because of evidence
of loss of cholinergic neurons
 Tacrine, donepezil, rivastigmine, and
galantamine are used as these are
cholinesterase inhibitors
 ADRs include nausea, vomiting, and
peripheral cholinomimetics effects
 Memantine binds to NMDA and produce
noncompetitive blockade and better tolerated
and less toxic than cholinestrase inhibitors

40.  Glaucoma is most common in elderly but
treatment is same as that for glaucoma of earlier
onset
 Age-related macular degeneration(AMD) is the
most common cause of blindness in elderly
patients
 Two types
1.wet form
2.dry form
 Cause of AMD is not known but smoking and
oxidative stress has long been thought to play a
role

41.  So antioxidants have been used to prevent or
delay the onset of AMD
 Oral formulations of vitamins C and E, beta-
carotene, zinc oxide are available
 Now laser phototherapy and antibiotics are
used
 Antibiotics bevacizumab, ranibizumab and
pegabtanib are approved for AMD
 these agents are injected into vitreous for
local effect

42.  Balance between overprescribing and
underprescribing
◦ Correct drug
◦ Correct dose
◦ Targets appropriate condition
◦ Is appropriate for the patient
Avoid “a pill for every ill”
Always consider non-pharmacologic therapy

43.  Polypharmacy
 Multiple co-morbid conditions
 Prior adverse drug event
 Low body weight or body mass index
 Age > 85 years
 Estimated CrCl <50 mL/min

44.  Absorption may be  or 
 Drugs with similar effects can result additive
effects
 Drugs with opposite effects can antagonize
each other
 Drug metabolism may be inhibited or induced

45. Combination Risk
ACE inhibitor + potassium Hyperkalemia
ACE inhibitor + K sparing diuretic Hyperkalemia, hypotension
Digoxin + antiarrhythmic Bradycardia, arrhythmia
Digoxin + diuretic
Antiarrhythmic + diuretic
Electrolyte imbalance; arrhythmia
Diuretic + diuretic Electrolyte imbalance; dehydration
Benzodiazepine + antidepressant
Benzodiazepine + antipsychotic
Sedation; confusion; falls
CCB/nitrate/vasodilator/diuretic Hypotension

46.  Obesity alters Vd of lipophilic drugs
 Ascites alters Vd of hydrophilic drugs
 Dementia may  sensitivity, induce
paradoxical reactions to drugs with CNS or
anticholinergic activity
 Renal or hepatic impairment may impair
metabolism and excretions of drugs
 Drugs may exacerbate a medical condition

47. Combination Risk
NSAIDs + CHF
Thiazolidinediones + CHF
Fluid retention; CHF exacerbation
BPH + anticholinergics Urinary retention
CCB + constipation
Narcotics + constipation
Anticholinergics + constipation
Exacerbation of constipation
Metformin + CHF Hypoxia; increased risk of lactic
acidosis
NSAIDs + gastropathy Increased ulcer and bleeding risk
NSAIDs + HTN Fluid retention; decreased
effectiveness of diuretics

48.  Avoid prescribing prior to diagnosis
 Start with a low dose
 Avoid starting 2 agents at the same time
 Reach therapeutic dose before switching or
adding agents
 Consider non-pharmacologic agents

49.  Review medications regularly and each time a
new medication started or dose is changed
 Maintain accurate medication records (include
vitamins, OTCs, and herbals)

50.  Suggest physician prescribe combination
drugs or long-acting forms
◦ Fewer pills to remember
 Suggest re-evaluation of medications
periodically
 Encourage client to use one pharmacy
 New medications
◦ Good information
◦ Encourage follow up

51.  There are several practical obstacles to
compliance that the prescriber must recognize
◦ Forgetfulness
◦ Prior experience
◦ Physical disabilities
 Recommendations to improve compliance
◦ Take careful drug history
◦ Prescribe only for a specific and rational indication
◦ Define goal of drug therapy
◦ High index of suspicion regarding drug reactions and
interactions
◦ Simplify drug regimen

52.  Avoid newer, more expensive medications
that are not shown to be superior to less
expensive generic alternatives
 Simplify the regimen
 Utilize pill organizers or drug calendars
 Educate patient on medication purpose,
benefits, safety, and potential ADEs

53.  Basic and Clinical Pharmacology by Bertram
G. Katzung Susan B. Master