4. ď˝ Physiologic change
⌠Decreased gastric acidity
⌠Decreased gastrointestinal blood flow
⌠Delayed gastric emptying
⌠Slowed intestinal transit time
ď˝ 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. ď˝ Decreased Total body water
⌠Increased Plasma Conc. of water soluble drugs
⌠Lower doses are required: Lithium, digoxin, ethanol, etc
ď˝ Decreased Lean body mass
⌠Increased Volume Distribution, Longer (t½) of water soluble
drugs
⌠Accumulation into fat of lipid soluble drugs: Benzos, etc
ď˝ Decreased Serum Albumin
⌠Increased unbound fraction of highly protein bound drugs
⌠Binds acidic drugs: warfarin, phenytoin, digitalis, etc
ď˝ Decreased Alpha1 Acid glycoprotein
⌠Increased unbound fraction of highly protein bound drugs
⌠-Binds basic drugs: lidocaine and propranolol, etc
6. ď Difficult to predict, depends on
ďGeneral health & nutritional status
ď Use of alcohol, medications
ďLong term exposure to environmental toxins/pollutants
ď Aging causes decreased liver mass/ hepatic blood
flow
ďDelayed/reduced metabolism of drugs
ďHigher plasma levels
ďGreatest changes in phase 1 reaction those carry out
microsomal p450 enzyme system
ďDecline in liver ability to recover from injury
ď Lower serum protein levels
ďLoss of protein binding
ď Idiosyncratic reactions
7. ď˝ Metabolic clearance of drugs by the liver may
be reduced due to:
⌠decreased hepatic blood flow
⌠decreased liver size and mass
ď˝ Examples: morphine, meperidine, metoprolol,
propranolol, verapamil, amitryptyline,
nortriptyline
8. ď˝ 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. ď˝ Physiologic change
⌠Decreased GFR
⌠Decreased renal blood flow
⌠Decreased renal mass
ď˝ General clinical effect
⌠Decreased clearance, Increased (t½) of renally
eliminated drugs
10. ď˝ Creatinine clearance (CrCl) is used to
estimate glomerular rate
ď˝ Serum creatinine alone not accurate in the
elderly
⌠ď lean body mass ď lower creatinine production
⌠ď glomerular filtration rate
ď˝ Serum creatinine stays in normal range,
masking change in creatinine clearance
11. ď˝ Measure
⌠Time consuming
⌠Requires 24 hr urine collection
ď˝ Estimate
⌠Cockroft Gault equation
(IBW in kg) x (140-age)
------------------------------ x (0.85 for
females)
72 x (Scr in mg/dL)
12. ď˝ Pharmacodynamic changes in the elderly have
been less extensively studied
ď˝ Evidence of enhanced end-organ
responsiveness or âsensitivityâ to medications
with aging
ď˝ Enhanced âsensitivityâ 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. ď˝ Age-related changes:
⌠ď sensitivity to sedation and psychomotor
impairment with benzodiazepines
⌠ď level and duration of pain relief with narcotic
agents
⌠ď drowsiness with alcohol
⌠ď sensitivity to anti-cholinergic agents
⌠ď cardiac sensitivity to digoxin
14. ď Cognitive changes associated with vascular
and other pathology
ď Economic stresses with greatly associated
with reduced income or due increased
expenses due to illness
ď Loss of spouse
15. ď˝ Positive relationship between number of drugs
taken and incidence
ď˝ Overall incidence is estimated to be at least twice
that in the younger population
ď˝ Prescribing errors
⌠Polypharmacy
⌠Drug interactions with other prescriptions
⌠Unawareness of age related physiologic changes
ď˝ Drug usage errors
⌠âHidden ingredientsâ: 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. ď˝ Economic factors
⌠May have to choose between food and medications
ď OTCs instead of expensive doctor visits
ď Use of outdated medications
ď Use of home remedies
ď Share medications
ď Nutritional status may affect how body metabolizes
medications
18. ď˝ 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
ď˝ Excessive use of drugs
ď˝ Overdose of a drug
19. ď˝ Risks of problems:
⌠Medication errors
ď Wrong drug, time, route
⌠Adverse effects from each drug
ď Polypharmacy primary reason for adverse reactions
⌠Adverse interactions between drugs
20. ď˝ CNS drugs
⌠Sedative-hypnotics: Benzodiazepines and barbiturates
⌠Analgesics: Opioids
⌠Antipsychotic, antidepressants: Haloperidol, lithium, TCAs
ď˝ Cardiovascular drugs
⌠Antihypertensives: Thiazides, beta-blockers
ď˝ Antiarrhythmic drugs
⌠Quinidine and procainamide: ďŻ clearance and ď (t½)
ď˝ Antimicrobial drugs
⌠Beta-lactams and aminoglycosides: ďŻ clearance
ď˝ Anti-inflammatory drugs
⌠NSAIDs: GI bleed and irritation
21. ďHalf life of many drugs benzodiazepine and barbiturates
increases 50-150% between age 30 and 70
ďAge related decline in renal and liver function both
contribute to to the reduction in elimination of these
compounds .
ďLorazepam and oxazepam may be less affected by these
change.
ďIt is generally believed that the elderly vary more in their
sensitivity to these sedatives on PD basis as well.
ďAdverse reactions like Ataxia and motor impairment
mostly present
22. ď 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. ď Phenothiazines and Heloperidol have been
heavily used in the management of variety of
psychiatric diseases in elderly .
ď Useful in treatments of some symptoms
associated with delirium, dementia, agitation,
combativeness however their use is not
satisfactory in geriatrics conditions.
ď Much of these improvements are simply reflect
the sedative effects
ď Phenothiazines often induce orhtostatic
hypotension because of their a-adrenergic
blocking effects.
25. ď˝ Antipsychotics
⌠Jaundice
⌠Extrapyramidal symptoms
⌠Sedation, dizziness (can lead to falls)
⌠Orthostatic hypotension
⌠Scaling skin on exposure to sunlight
(phenothiazines)
27. ď˝ Antihypertensive drugs
ď Systolic blood pressure increases with age in western
countries and in most culture in which salt intake is high
ď Drugs used for it are Thiazides ,calcium channel blocker ,beta
blockers etc
ď˝ ADRS related to these drugs
⌠Dizziness and falls
⌠Orthostatic hypotension
29. ď˝ Heart failure most common and lethal disease
in elderly
ď˝ Fear of this condition may be the one reason
why physicians overuse cardiac glycosides in
this age group
ď˝ 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. ď Treatment of arrhythmias in elderly is
particularly challenging due to
ď§ lack of good hemodynamic reserves'
ď§ Frequency of electrolyte disturbance
ď§ High prevalence of coronary disease
32. ď Following ADRS observed due to decreased
clearance and increased half life of
antiarrhythmics
⌠Confusion
⌠Slurred speech
⌠Light-headedness, seizures
⌠hypotension
33. ď˝ Age related changes contributes to incidence
of infection in elderly patients
ď˝ Reduction in host defense manifested in the
increase in both serious infection and cancer
ď˝ In the lungs age dependent decrease in the
mucociliary clearance significantly increase in
susceptibility of infection
ď˝ In urinary tract,incidence of infections is
greatly increased by urinary retention
34. ď˝ Since 1940, antimicrobial have contributed
more to prolong the life because they can
compensate to some extent for this
deterioration in natural defenses
ď˝ Because most antibiotics are excreted renal
route so change in half life may occur so
adverse reactions takes place
35. ď˝ Osteoarthritis most commonly present in
elderly patients
ď˝ NSAIDs and corticosteroids are mostly used
ď˝ Corticosteroids are extremely useful in
elderly who cannot tolerate full doses of
NSAIDs however consistently cause increase
in osteoporosis
38. ď˝ Disease is characterized by progressive
impairment of memory and cognitive
function, prevalence increases with age
ď˝ 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
ď˝ Many methods of treatment of Alzheimer`s
disease has been explored
39. ď˝ Most attention has been focused on the
cholinomimetics drugs because of evidence
of loss of cholinergic neurons
ď˝ Tacrine, donepezil, rivastigmine, and
galantamine are used as these are
cholinesterase inhibitors
ď˝ ADRs include nausea, vomiting, and
peripheral cholinomimetics effects
ď˝ Memantine binds to NMDA and produce
noncompetitive blockade and better tolerated
and less toxic than cholinestrase inhibitors
40. ď˝ Glaucoma is most common in elderly but
treatment is same as that for glaucoma of earlier
onset
ď˝ Age-related macular degeneration(AMD) is the
most common cause of blindness in elderly
patients
ď˝ Two types
1.wet form
2.dry form
ď Cause of AMD is not known but smoking and
oxidative stress has long been thought to play a
role
41. ď˝ So antioxidants have been used to prevent or
delay the onset of AMD
ď˝ Oral formulations of vitamins C and E, beta-
carotene, zinc oxide are available
ď˝ Now laser phototherapy and antibiotics are
used
ď˝ Antibiotics bevacizumab, ranibizumab and
pegabtanib are approved for AMD
ď˝ these agents are injected into vitreous for
local effect
42. ď˝ Balance between overprescribing and
underprescribing
⌠Correct drug
⌠Correct dose
⌠Targets appropriate condition
⌠Is appropriate for the patient
Avoid âa pill for every illâ
Always consider non-pharmacologic therapy
43. ď˝ Polypharmacy
ď˝ Multiple co-morbid conditions
ď˝ Prior adverse drug event
ď˝ Low body weight or body mass index
ď˝ Age > 85 years
ď˝ Estimated CrCl <50 mL/min
44. ď˝ Absorption may be ď or ď
ď˝ Drugs with similar effects can result additive
effects
ď˝ Drugs with opposite effects can antagonize
each other
ď˝ Drug metabolism may be inhibited or induced
46. ď˝ Obesity alters Vd of lipophilic drugs
ď˝ Ascites alters Vd of hydrophilic drugs
ď˝ Dementia may ď sensitivity, induce
paradoxical reactions to drugs with CNS or
anticholinergic activity
ď˝ Renal or hepatic impairment may impair
metabolism and excretions of drugs
ď˝ Drugs may exacerbate a medical condition
48. ď˝ Avoid prescribing prior to diagnosis
ď˝ Start with a low dose
ď˝ Avoid starting 2 agents at the same time
ď˝ Reach therapeutic dose before switching or
adding agents
ď˝ Consider non-pharmacologic agents
49. ď˝ Review medications regularly and each time a
new medication started or dose is changed
ď˝ Maintain accurate medication records (include
vitamins, OTCs, and herbals)
50. ď˝ Suggest physician prescribe combination
drugs or long-acting forms
⌠Fewer pills to remember
ď˝ Suggest re-evaluation of medications
periodically
ď˝ Encourage client to use one pharmacy
ď˝ New medications
⌠Good information
⌠Encourage follow up
51. ď˝ There are several practical obstacles to
compliance that the prescriber must recognize
⌠Forgetfulness
⌠Prior experience
⌠Physical disabilities
ď˝ 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. ď˝ Avoid newer, more expensive medications
that are not shown to be superior to less
expensive generic alternatives
ď˝ Simplify the regimen
ď˝ Utilize pill organizers or drug calendars
ď˝ Educate patient on medication purpose,
benefits, safety, and potential ADEs
53. ď Basic and Clinical Pharmacology by Bertram
G. Katzung Susan B. Master