geriatrics pharmacology


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Page 1: Geriatrics pharmacology




Page 2: Geriatrics pharmacology

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

Adults >65 years old

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Alzheimer`s disease Parkinsonism Stroke Vascular dementia Visual impairment specially cataracts and macular

degeneration Atherosclerosis Arthritis Heart failure Fractures Cancer Diabetes Heart failure

Diseases with increased incidence in elderly

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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

Physiologic Changes of Aging Affecting Absorption

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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

Physiologic Changes of Aging Affecting Distribution

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Difficult to predict, depends onGeneral health & nutritional status Use of alcohol, medicationsLong term exposure to environmental toxins/pollutants

Aging causes decreased liver mass/ hepatic blood flowDelayed/reduced metabolism of drugsHigher plasma levelsGreatest changes in phase 1 reaction those carry out

microsomal p450 enzyme systemDecline in liver ability to recover from injury

Lower serum protein levelsLoss of protein binding

Idiosyncratic reactions

Physiological changes of aging affecting metabolism

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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

Aging Effects on Hepatic Metabolism

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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

Physiological changes of aging affecting elimination

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Physiologic change◦ Decreased GFR◦ Decreased renal blood flow◦ Decreased renal mass

General clinical effect◦ Decreased clearance, Increased (t½) of renally

eliminated drugs

Physiologic Changes of Aging Affecting Elimination

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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

Estimating GFR in the Elderly

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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)

Determining Creatinine Clearance

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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

Pharmacodynamic changes in elderly

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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

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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

Behavioral and lifestyle changes

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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

Major Reasons for Adverse Drug Reactions in the Elderly

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Factors contributing to adverse drug reactions

in elderly patients


How many prescription medications are too many? >4 or >6 Many elderly people receive 12 medications per day

Heart, kidney, liver, thyroid

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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


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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


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Risks of problems:◦ Medication errors

Wrong drug, time, route

◦ Adverse effects from each drug Polypharmacy primary reason for adverse reactions

◦ Adverse interactions between drugs


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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

Major Drug Groups Requiring Monitoring

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Sedative hypnoticsHalf life of many drugs benzodiazepine and barbiturates increases 50-150% between age 30 and 70Age 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

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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 .


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

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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.

Antipsychotics and antidepressants

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


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

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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

Cardiovascular drugs

ADRS related to these drugs ◦ Dizziness and falls◦ Orthostatic hypotension

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Diuretics◦ Fluid/electrolyte disorders◦ Dehydration◦ Hypotension◦ Thiazide diuretics can increase blood glucose

levels (more insulin for diabetics)

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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

Positive inotropic agents

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

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Treatment of arrhythmias in elderly is particularly challenging due to

lack of good hemodynamic reserves' Frequency of electrolyte disturbance High prevalence of coronary disease

Antiarrhythmic drugs

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Following ADRS observed due to decreased clearance and increased half life of antiarrhythmics

◦ Confusion◦ Slurred speech◦ Light-headedness, seizures◦ hypotension

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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

Antimicrobial agents

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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

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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

Anti-inflammatory drugs

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NSAIDs◦ Prolong bleeding

Gastric discomfort, bleeding◦ Increased risk of toxicity (with impaired renal


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

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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

Drugs used in Alzheimer`s disease

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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

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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

Drugs used in Glaucoma and macular degeneration

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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

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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

Optimal Pharmacotherapy

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

Patient Risk Factors for ADEs

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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


Concepts in Drug-Drug Interactions

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Common Drug-Drug InteractionsCombination RiskACE inhibitor + potassium HyperkalemiaACE inhibitor + K sparing diuretic Hyperkalemia, hypotensionDigoxin + antiarrhythmic Bradycardia, arrhythmiaDigoxin + diureticAntiarrhythmic + diuretic

Electrolyte imbalance; arrhythmia

Diuretic + diuretic Electrolyte imbalance; dehydration

Benzodiazepine + antidepressantBenzodiazepine + antipsychotic

Sedation; confusion; falls

CCB/nitrate/vasodilator/diuretic Hypotension

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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

Drug-Disease Interactions

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Common Drug-Disease InteractionsCombination RiskNSAIDs + CHFThiazolidinediones + CHF

Fluid retention; CHF exacerbation

BPH + anticholinergics Urinary retentionCCB + constipationNarcotics + constipationAnticholinergics + constipation

Exacerbation of constipation

Metformin + CHF Hypoxia; increased risk of lactic acidosis

NSAIDs + gastropathy Increased ulcer and bleeding riskNSAIDs + HTN Fluid retention; decreased

effectiveness of diuretics

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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

Principles of Prescribing in the Elderly

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Review medications regularly and each time a new medication started or dose is changed

Maintain accurate medication records (include vitamins, OTCs, and herbals)

Preventing Polypharmacy

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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

If client taking > five meds regularly

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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


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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

Enhancing Medication Adherence

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