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 .
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)
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
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
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
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
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