Pharmacology in old age, principals and important points

1. Multidrug Use in theMultidrug Use in the
ElderlyElderly
Faisal HussainiFaisal Hussaini
Faisal GhamdiFaisal Ghamdi
Abdullah Ghouth-AliAbdullah Ghouth-Ali
Saif GhamdiSaif Ghamdi

2. ObjectivesObjectives

3. AcknowlegmentAcknowlegment
The development of this presentation was made possibleThe development of this presentation was made possible
through a help of :through a help of :
Torronto Notes on Elderly pharmacology.Torronto Notes on Elderly pharmacology.
Dr. Rayf Abulezz, B.S, Pharm.D., BCPS ConsultantDr. Rayf Abulezz, B.S, Pharm.D., BCPS Consultant
Clinical Pharmacist, College of Medicine, KSAU-HSClinical Pharmacist, College of Medicine, KSAU-HS
Dr. Linda Farho, Pharm.D. College of Pharmacy,Dr. Linda Farho, Pharm.D. College of Pharmacy,
University of Nebraska Medical Center.University of Nebraska Medical Center.

4. The Aging ImperativeThe Aging Imperative
 Persons aged 65y andPersons aged 65y and
older constitute 13% ofolder constitute 13% of
the population andthe population and
purchase 33% of allpurchase 33% of all
prescription medicationsprescription medications
 By 2040, 25% of theBy 2040, 25% of the
population will purchasepopulation will purchase
50% of all prescription50% of all prescription
drugsdrugs

5. Challenges of Geriatric PharmacotherapyChallenges of Geriatric Pharmacotherapy
 New drugs available each yearNew drugs available each year
 Changing managed-care formulasChanging managed-care formulas
 Advanced understanding of drug-drug interactionsAdvanced understanding of drug-drug interactions
 Multiple co-morbid statesMultiple co-morbid states
 PolypharmacyPolypharmacy
 Medication complianceMedication compliance
 Effects of aging physiology on drug therapyEffects of aging physiology on drug therapy
 Medication costMedication cost

6. Pharmacokinetics (PK)Pharmacokinetics (PK)
 AbsorptionAbsorption
– bioavailabilitybioavailability: the fraction of a drug dose reaching the systemic: the fraction of a drug dose reaching the systemic
circulationcirculation
 DistributionDistribution
– locations in the body a drug penetrates expressed as volumelocations in the body a drug penetrates expressed as volume
per weight (e.g. L/kg)per weight (e.g. L/kg)
 MetabolismMetabolism
– drug conversion to alternate compounds which may bedrug conversion to alternate compounds which may be
pharmacologically active or inactivepharmacologically active or inactive
 EliminationElimination
– a drug’s final route(s) of exit from the body expressed in terms ofa drug’s final route(s) of exit from the body expressed in terms of
half-life or clearancehalf-life or clearance

7. Effects of Aging on AbsorptionEffects of Aging on Absorption
 Rate of absorption mayRate of absorption may
be delayedbe delayed
– Lower peak concentrationLower peak concentration
– Delayed time to peakDelayed time to peak
concentrationconcentration
 Overall amount absorbedOverall amount absorbed
(bioavailability) is(bioavailability) is
unchangedunchanged

8. Hepatic First-Pass MetabolismHepatic First-Pass Metabolism
 For drugs with extensive first-passFor drugs with extensive first-pass
metabolism, bioavailability may increasemetabolism, bioavailability may increase
because less drug is extracted by the liverbecause less drug is extracted by the liver
– Decreased liver massDecreased liver mass
– Decreased liver blood flowDecreased liver blood flow

9. Factors Affecting AbsorptionFactors Affecting Absorption
 Route of administrationRoute of administration
 What it taken with the drugWhat it taken with the drug
– Divalent cations (Ca, Mg, Fe)Divalent cations (Ca, Mg, Fe)
– Food, enteral feedingsFood, enteral feedings
– Drugs that influence gastric pHDrugs that influence gastric pH
– Drugs that promote or delay GI motilityDrugs that promote or delay GI motility
 Comorbid conditionsComorbid conditions
 Increased GI pHIncreased GI pH
 Decreased gastric emptyingDecreased gastric emptying
 DysphagiaDysphagia

10. Effects of Aging on Volume ofEffects of Aging on Volume of
Distribution (Vd)Distribution (Vd)
Aging EffectAging Effect Vd EffectVd Effect ExamplesExamples
⇓⇓ body waterbody water ⇓⇓ Vd for hydrophilicVd for hydrophilic
drugsdrugs
ethanol, lithiumethanol, lithium
⇓⇓ lean body masslean body mass ⇓⇓ Vd for for drugsVd for for drugs
that bind to musclethat bind to muscle
digoxindigoxin
⇑⇑ fat storesfat stores ⇑⇑ Vd for lipophilicVd for lipophilic
drugsdrugs
diazepam, trazodonediazepam, trazodone
⇓⇓ plasma proteinplasma protein
(albumin)(albumin)
⇑⇑ % of unbound or% of unbound or
free drug (active)free drug (active)
diazepam, valproic acid,diazepam, valproic acid,
phenytoin, warfarinphenytoin, warfarin
⇑⇑ plasma proteinplasma protein
((αα11-acid glycoprotein)-acid glycoprotein)
⇓⇓ % of unbound or% of unbound or
free drug (active)free drug (active)
quinidine, propranolol,quinidine, propranolol,
erythromycin, amitriptylineerythromycin, amitriptyline

11. Aging Effects on HepaticAging Effects on Hepatic
MetabolismMetabolism
 Metabolic clearance of drugs by the liverMetabolic clearance of drugs by the liver
may be reduced due to:may be reduced due to:
– decreased hepatic blood flowdecreased hepatic blood flow
– decreased liver size and massdecreased liver size and mass
 ExamplesExamples: morphine, meperidine,: morphine, meperidine,
metoprolol, propranolol, verapamil,metoprolol, propranolol, verapamil,
amitryptyline, nortriptylineamitryptyline, nortriptyline

12. Other Factors Affecting DrugOther Factors Affecting Drug
MetabolismMetabolism
 GenderGender
 Comorbid conditionsComorbid conditions
 SmokingSmoking
 DietDiet
 Drug interactionsDrug interactions
 RaceRace
 FrailtyFrailty

13. Effects of Aging on the KidneyEffects of Aging on the Kidney
 Decreased kidney sizeDecreased kidney size
 Decreased renal blood flowDecreased renal blood flow
 Decreased number of functional nephronsDecreased number of functional nephrons
 Decreased tubular secretionDecreased tubular secretion
 Result:Result: ⇓⇓ glomerular filtration rate (GFR)glomerular filtration rate (GFR)
 Decreased drug clearanceDecreased drug clearance: atenolol,: atenolol,
gabapentin, H2 blockers, digoxin, allopurinol,gabapentin, H2 blockers, digoxin, allopurinol,
quinolonesquinolones

14. Pharmacodynamics (PD)Pharmacodynamics (PD)
 Definition: the time course and intensity ofDefinition: the time course and intensity of
pharmacologic effect of a drugpharmacologic effect of a drug
 Age-related changes:Age-related changes:
⇑⇑ sensitivity to sedation and psychomotor impairmentsensitivity to sedation and psychomotor impairment
withwith benzodiazepinesbenzodiazepines
⇑⇑ level and duration of pain relief withlevel and duration of pain relief with narcotic agentsnarcotic agents
⇑⇑ drowsiness and lateral sway withdrowsiness and lateral sway with alcoholalcohol
⇓⇓ HR response toHR response to beta-blockersbeta-blockers
⇑⇑ sensitivity tosensitivity to anti-cholinergic agentsanti-cholinergic agents
⇑⇑ cardiac sensitivity tocardiac sensitivity to digoxindigoxin

15. PK and PD SummaryPK and PD Summary
 PK and PD changes generally result inPK and PD changes generally result in
decreased clearance and increaseddecreased clearance and increased
sensitivity to medications in older adultssensitivity to medications in older adults
 Use of lower doses, longer intervals,Use of lower doses, longer intervals,
slower titration are helpful in decreasingslower titration are helpful in decreasing
the risk of drug intolerance and toxicitythe risk of drug intolerance and toxicity
 Careful monitoring is necessary to ensureCareful monitoring is necessary to ensure
successful outcomessuccessful outcomes

16. Optimal PharmacotherapyOptimal Pharmacotherapy
 Balance between overprescribing andBalance between overprescribing and
underprescribingunderprescribing
– Correct drugCorrect drug
– Correct doseCorrect dose
– Targets appropriate conditionTargets appropriate condition
– Is appropriate for the patientIs appropriate for the patient
Avoid “a pill for every ill”Avoid “a pill for every ill”
Always consider non-pharmacologic therapyAlways consider non-pharmacologic therapy

17. Consequences of OverprescribingConsequences of Overprescribing
 Adverse drug events (ADEs)Adverse drug events (ADEs)
 Drug interactionsDrug interactions
 Duplication of drug therapyDuplication of drug therapy
 Decreased quality of lifeDecreased quality of life
 Unnecessary costUnnecessary cost
 Medication non-adherenceMedication non-adherence

18. Adverse Drug Events (ADEs)Adverse Drug Events (ADEs)
 Responsible for 5-28% ofResponsible for 5-28% of
acute geriatric hospitalacute geriatric hospital
admissionsadmissions
 Greater than 95% of ADEsGreater than 95% of ADEs
in the elderly are consideredin the elderly are considered
predictable andpredictable and
approximately 50% areapproximately 50% are
considered preventableconsidered preventable
 Most errors occur at theMost errors occur at the
ordering and monitoringordering and monitoring
stagesstages

19. Most Common MedicationsMost Common Medications
Associated with ADEs in the ElderlyAssociated with ADEs in the Elderly
 Opioid analgesicsOpioid analgesics
 NSAIDsNSAIDs
 AnticholinergicsAnticholinergics
 BenzodiazepinesBenzodiazepines
 AlsoAlso: cardiovascular agents, CNS agents,: cardiovascular agents, CNS agents,
and musculoskeletal agentsand musculoskeletal agents
Adverse Drug Reaction Risk Factors in Older Outpatients. Am J Ger Pharmacotherapy 2003;1(2):82-89.Adverse Drug Reaction Risk Factors in Older Outpatients. Am J Ger Pharmacotherapy 2003;1(2):82-89.

20. The Beers CriteriaThe Beers Criteria
High Potential forHigh Potential for
Severe ADESevere ADE
High Potential forHigh Potential for
Less Severe ADELess Severe ADE
amitriptylineamitriptyline
chlorpropamidechlorpropamide
digoxin >0.125mg/ddigoxin >0.125mg/d
disopyramidedisopyramide
GI antispasmodicsGI antispasmodics
meperidinemeperidine
methyldopamethyldopa
pentazocinepentazocine
ticlopidineticlopidine
antihistaminesantihistamines
diphenhydraminediphenhydramine
dipyridamoledipyridamole
ergot mesyloidsergot mesyloids
indomethacinindomethacin
muscle relaxantsmuscle relaxants

21. Patient Risk Factors for ADEsPatient Risk Factors for ADEs
 PolypharmacyPolypharmacy
 Multiple co-morbid conditionsMultiple co-morbid conditions
 Prior adverse drug eventPrior adverse drug event
 Low body weight or body mass indexLow body weight or body mass index
 Age > 85 yearsAge > 85 years
 Estimated CrCl <50 mL/minEstimated CrCl <50 mL/min

22. SummarySummary
 Successful pharmacotherapy means usingSuccessful pharmacotherapy means using
the correct drug at the correct dose for thethe correct drug at the correct dose for the
correct indication in an individual patientcorrect indication in an individual patient
 Age alters PK and PDAge alters PK and PD
 ADEs are common among the elderlyADEs are common among the elderly
 Risk of ADEs can be minimized byRisk of ADEs can be minimized by
appropriate prescribingappropriate prescribing

23. QuestionsQuestions