terapi farmakologi pada geriatri - copy
TRANSCRIPT
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dr. T. Mamfaluti, SpPD., M. Kes
TERAPI FARMAKOLOGI TERAPI FARMAKOLOGI PADA GERIATRIPADA GERIATRI
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TERAPI FARMAKOLOGI PADA GERIATRI
– Geriatri ≥ 65 tahun, 75 s/d 85 (Old old), ≥ 85 tahun( Oldest old),
– Cabang kedokteran yg konsen thd aging proses:• Pencegahan, diagnosis dan terapi.
– Objektif:• Pengaruh usia thd farmakokinetik dan farmakodinamik• Memahami prinsip-prinsip peresepan obat pd orang tua• Multiple co-morbid state• Polifarmasi• Resiko adverse drug events• Tingkat kepatuhan minum obat• Biaya
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• Fakta berkaitan dgn geriatri– Pasien berumur 65 th atau lebih mencakup 13%
dari populasi dan membelanjakan 33% obat-obatan yg diresepkan.
– Tahun 2040, geriatri mencakup 25% populasi dan membelanjakan 50% obat-obat yg diresepkan.
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Pharmacokinetics (PK)• Absorption
– bioavailability: the fraction of a drug dose reaching the systemic circulation
• Distribution– locations in the body a drug penetrates expressed as volume per
weight (e.g. L/kg)
• Metabolism– drug conversion to alternate compounds which may be
pharmacologically active or inactive
• Elimination– a drug’s final route(s) of exit from the body expressed in terms of half-
life or clearance
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Efek usia thd Absorpsi
• Kecepatan absorpsi terlambat:– Konsentrasi puncak obat
lebih rendah– Waktu mencapai konsentrasi
puncak telambat• Jumlah obat yg diabsorpsi
(bioavailability) tidak berubah
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Hepatic First-Pass Metabolism
• For drugs with extensive first-pass metabolism, bioavailability may increase because less drug is extracted by the liver– Decreased liver mass– Decreased liver blood flow
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Faktor-faktor yg mempengaruhi absorpsi obat
• Route of administration• What it taken with the drug– Divalent cations (Ca, Mg, Fe)– Food, enteral feedings– Drugs that influence gastric pH– Drugs that promote or delay GI motility
• Comorbid conditions• Increased GI pH• Decreased gastric emptying• Dysphagia
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Effects of Aging on Volume of Distribution (Vd)
Aging EffectAging Effect Vd EffectVd Effect ExamplesExamples body waterbody water Vd for Vd for
hydrophilic hydrophilic drugsdrugs
ethanol, lithiumethanol, lithium
lean body lean body mass(bb)mass(bb)
Vd for for Vd for for drugs that bind drugs that bind to muscleto muscle
digoxindigoxin
fat storesfat stores Vd for Vd for lipophilic drugslipophilic drugs
diazepam, trazodonediazepam, trazodone
plasma protein plasma protein (albumin)(albumin)
% of unbound % of unbound or free drug or free drug (active)(active)
diazepam, valproic diazepam, valproic acid, phenytoin, acid, phenytoin, warfarinwarfarin
plasma protein plasma protein
((11-acid -acid glycoprotein)glycoprotein)
% of unbound % of unbound or free drug or free drug (active)(active)
quinidine, propranolol, quinidine, propranolol, erythromycin, erythromycin, amitriptylineamitriptyline
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Aging Effects on Hepatic Metabolism
• Metabolic clearance of drugs by the liver may be reduced(menurun) due to:– decreased hepatic blood flow(aliran)– decreased liver size and mass
• Examples: morphine, meperidine, metoprolol, propranolol, verapamil, amitryptyline, nortriptyline
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Metabolic Pathways
PathwayPathway EffectEffect ExamplesExamples
Phase IPhase I: oxidation, : oxidation, hydroxylation, hydroxylation, dealkylation, dealkylation, reductionreduction
Conversion to Conversion to metabolites of metabolites of lesser, equal, or lesser, equal, or greatergreater
diazepam, diazepam, quinidine, quinidine, piroxicam, piroxicam, theophyllinetheophylline
Phase IIPhase II: : glucuronidation, glucuronidation, conjugation, or conjugation, or acetylationacetylation
Conversion to Conversion to inactive inactive metabolitesmetabolites
lorazepam, lorazepam, oxazepam, oxazepam, temazepamtemazepam
** NOTE: Medications undergoing Phase II hepatic metabolism are generally preferred in the elderly due to inactive metabolites (no accumulation)
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Other Factors Affecting Drug Metabolism
• Gender• Comorbid conditions• Smoking• Diet• Drug interactions• Race• Frailty(kelemahan)
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Concepts in Drug Elimination
• Half-life– time for serum concentration of drug to decline by
50% (expressed in hours)
• Clearance– volume of serum from which the drug is removed
per unit of time (mL/min or L/hr)
• Reduced elimination drug accumulation and toxicity
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Effects of Aging on the Kidney
• Decreased kidney size• Decreased renal blood flow• Decreased number of functional nephrons• Decreased tubular secretion• Result: glomerular filtration rate (GFR)• Decreased drug clearance: atenolol, gabapentin, H2
blockers, digoxin, allopurinol, quinolones
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Estimating GFR in the Elderly
• 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
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Determining Creatinine Clearance
• 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)
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Example: Creatinine Clearance vs. Age in a 55 kg Woman
30301.11.19090
41411.11.17070
53531.11.15050
65651.11.13030
CrClCrClScrScrAgeAge
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Pharmacodynamics (PD)
• Definition: the time course and intensity of pharmacologic effect of a drug
• Age-related changes:– sensitivity to sedation and psychomotor
impairment(perusakan) with benzodiazepines– level and duration of pain relief with narcotic agents– drowsiness and lateral sway with alcohol– HR response to beta-blockers– sensitivity to anti-cholinergic agents– cardiac sensitivity to digoxin
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PK and PD Summary
• PK and PD changes generally result in decreased clearance and increased sensitivity to medications in older adults
• Use of lower doses, longer intervals, slower titration are helpful in decreasing the risk of drug intolerance and toxicity
• Careful monitoring is necessary to ensure successful outcomes
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Optimal Pharmacotherapy
• 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
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Consequences of Overprescribing
• Adverse drug events (ADEs)• Drug interactions• Duplication of drug therapy• Decreased quality of life• Unnecessary cost• Medication non-adherence
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Adverse Drug Events (ADEs)
• Responsible for 5-28% of acute geriatric hospital admissions
• Greater than 95% of ADEs in the elderly are considered predictable and approximately 50% are considered preventable
• Most errors occur at the ordering and monitoring stages
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Most Common Medications Associated with ADEs in the Elderly
• Opioid analgesics• NSAIDs• Anticholinergics• Benzodiazepines• Also: cardiovascular agents, CNS agents, and
musculoskeletal agents
Adverse Drug Reaction Risk Factors in Older Outpatients. Am J Ger Pharmacotherapy 2003;1(2):82-89.
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The Beers CriteriaHigh Potential for High Potential for
Severe ADESevere ADEHigh Potential for High Potential for
Less Severe ADELess Severe ADE
amitriptylineamitriptyline
chlorpropamidechlorpropamide
digoxin >0.125mg/ddigoxin >0.125mg/d
disopyramidedisopyramide
GI antispasmodicsGI antispasmodics
meperidinemeperidine
methyldopamethyldopa
pentazocinepentazocine
ticlopidineticlopidine
antihistamines antihistamines
diphenhydraminediphenhydramine
dipyridamoledipyridamole
ergot mesyloidsergot mesyloids
indomethacinindomethacin
muscle relaxantsmuscle relaxants
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Patient Risk Factors for ADEs
• Polypharmacy• Multiple co-morbid conditions• Prior adverse drug event• Low body weight or body mass index• Age > 85 years• Estimated CrCl <50 mL/min
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Drug-Drug Interactions (DDIs)
• May lead to adverse drug events• Likelihood as number of medications • Most common DDIs:– cardiovascular drugs– psychotropic drugs
• Most common drug interaction effects:– confusion – cognitive impairment– hypotension– acute renal failure
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Concepts in Drug-Drug Interactions
• 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
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Common Drug-Drug Interactions
CombinationCombination RiskRiskACE inhibitor + potassiumACE inhibitor + potassium HyperkalemiaHyperkalemia
ACE inhibitor + K sparing ACE inhibitor + K sparing diureticdiuretic
Hyperkalemia, hypotensionHyperkalemia, hypotension
Digoxin + antiarrhythmicDigoxin + antiarrhythmic Bradycardia, arrhythmiaBradycardia, arrhythmia
Digoxin + diureticDigoxin + diuretic
Antiarrhythmic + diureticAntiarrhythmic + diureticElectrolyte imbalance; Electrolyte imbalance; arrhythmiaarrhythmia
Diuretic + diureticDiuretic + diuretic Electrolyte imbalance; Electrolyte imbalance; dehydrationdehydration
Benzodiazepine + antidepressantBenzodiazepine + antidepressant
Benzodiazepine + antipsychoticBenzodiazepine + antipsychoticSedation; confusion; fallsSedation; confusion; falls
CCB/nitrate/vasodilator/diureticCCB/nitrate/vasodilator/diuretic Hypotension Hypotension
Doucet J, Chassagne P, Trivalle C, et al. Drug-drug interactions related to hospital admissions in older adults: a prospective study of 1000 patients. J Am Geriatr Soc 1996;44(9):944-948.
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Drug-Disease Interactions
• 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
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Common Drug-Disease Interactions
CombinationCombination RiskRisk
NSAIDs + CHFNSAIDs + CHF
Thiazolidinediones + CHFThiazolidinediones + CHFFluid retention; CHF Fluid retention; CHF exacerbationexacerbation
BPH + anticholinergicsBPH + anticholinergics Urinary retentionUrinary retention
CCB + constipationCCB + constipation
Narcotics + constipationNarcotics + constipation
Anticholinergics + constipationAnticholinergics + constipation
Exacerbation of constipationExacerbation of constipation
Metformin + CHFMetformin + CHF Hypoxia; increased risk of lactic Hypoxia; increased risk of lactic acidosisacidosis
NSAIDs + gastropathyNSAIDs + gastropathy Increased ulcer and bleeding riskIncreased ulcer and bleeding risk
NSAIDs + HTNNSAIDs + HTN Fluid retention; decreased Fluid retention; decreased effectiveness of diureticseffectiveness of diuretics
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Principles of Prescribing in the Elderly
• Avoid prescribing prior to diagnosis• Start with a low dose and titrate slowly• Avoid starting 2 agents at the same time• Reach therapeutic dose before switching or
adding agents• Consider non-pharmacologic agents
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Peu di tuleh nyou.
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Prescribing Appropriately• Determine therapeutic endpoints and plan for assessment• Consider risk vs. benefit• Avoid prescribing to treat side effect of another drug• Use 1 medication to treat 2 conditions• Consider drug-drug and drug-disease interactions• Use simplest regimen possible• Adjust doses for renal and hepatic impairment• Use least expensive alternative
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Preventing Polypharmacy
• Review medications regularly and each time a new medication started or dose is changed
• Maintain accurate medication records (include vitamins, OTCs, and herbals)
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Non-Adherence
• Rate may be as high as 50% in the elderly
• Factors in non-adherence– Financial, cognitive, or functional status– Beliefs and understanding about disease and
medications
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Enhancing Medication Adherence
• Avoid newer, more expensive medications that are not shown to be superior to less expensive generic alternatives
• Simplify the regimen• Utilize drug calendars• Educate patient on medication purpose,
benefits, safety, and potential ADEs
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Summary
• Successful pharmacotherapy means using the correct drug at the correct dose for the correct indication in an individual patient
• Age alters PK and PD• ADEs are common among the elderly• Risk of ADEs can be minimized by appropriate
prescribing
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