Terapi Farmakologi Pada Geriatri

 

TERAPI FARMAKOLOGI PADA GERIATRI dr. T. Mamfaluti, SpPD., M. Kes

 

TERAPI FARMAKOLOGI PADA GERIATRI  –

 –

 Geriatri ≥ 65 tahun, 75 s/d 85 (Old old), ≥ 85 tahun( Oldest old), Cabang kedokteran yg konsen thd aging proses: •

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Pencegahan, Penceg ahan, diagnosis diagnosis dan terapi. terapi.

Objektif: •

Pengaruh usia thd farmakokinetik dan farmakodinamik

•

Memahami prinsip-prinsip peresepan obat pd orang tua

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Multiple co-morbid stat state e

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Polifarmasi

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Resiko adverse drug events

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Tingkat kepatuhan minum obat

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Biaya

 

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Fakta berkaitan dgn geriatri  –

 –

Pasien berumur 65 th atau lebih mencakup 13% dari populasi dan membelanjakan 33% obatobatan yg diresepkan. Tahun 2040, geriatri mencakup 25% populasi dan membelanjakan 50% obat-obat yg diresepkan. diresepkan.

 

Pharmacokinetics (PK) •

Absorption  –

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bioavailability: the fraction of bioavailability: o f a drug dose reaching the systemic systemic circulation

Distribution locations in the body a drug penetrates penetrates expressed as volume per  –

weight (e.g. L/kg) •

Metabolism  –

•

drug conversion conversion to alternate compounds which may be pharmacologically active or inactive

Elimination  –

a drug’ drug ’s final route(s) of exit from the body expressed expressed in terms of half -

life or clearance

 

Efek usia thd Absorpsi •

Kecepatan absorpsi terlambat:  –

 –

•

Konsentrasi lebih rendahpuncak obat Waktu mencapai konsentrasi puncak telambat

Jumlah obat yg diabsorpsi (bioavailability) (bioav ailability) tidak berubah

 

Hepatic First-Pass Metabolism •

For drugs with extensive first-pass first-pass metabolism, bioavailability may increase because less drug is extract extracted ed by the liver  –

Decreased liver mass

 –

Decreased liver blood flow

 

Faktor-faktor yg mempengaruhi absorpsi obat •

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Route of administration What it taken with the drug  –

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 –

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Divalent cations (Ca, Mg, Fe) Food, enteral feedings Drugs that influence gastric pH Drugs that promote or delay GI motility

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•

•

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Comorbid conditions Increased GI pH Decreased gastric emptying Dysphagia

 

Effects of Aging on Volume of Distribution (Vd)  Aging Effect

Vd Effect

Examples

 body water

 Vd for hydrophilic

ethanol, lithium

 lean body mass(bb)

drugs  Vd for for drugs that bind to muscle

digoxin

 fat stores

 Vd for lipophilic

diazepam, trazodone

 plasma protein (albumin)

drugs unbound or  % of unbound free drug (active)

diazepam, valproic acid, phenytoin, warfarin

 plasma protein

 % of unbound unbound or

quinidine, quinidine, propranolol,

( 1-acid glycoprotein)

free drug (active)

erythromycin, amitriptyline

 

 

 

Aging Effects on Hepatic Metabolism •

•

Metabolic clearance of drugs by the th e liver may be reduced(menurun) due to:  –

decreased hepatic blood flow(aliran)

 –

decreased liver size and mass

Examples: morphine, meperidine, metopr metoprolol, olol, propranolol, propr anolol, ver verapamil, apamil, amitryptyline, nortriptyline

 

Metabolic Pathways Pathway

Effect

Examples

Phase I: oxidation, hydroxylation, dealkylation, reduction

Conversion to metabolites metabol ites of lesser, lesser, equal, or greater

diazepam, quinidine, piroxicam, theophylline

Phase II: glucuronidation, Conversion to inactive metabolites conjugation, or acetylation

lorazepam, oxazepam, temazepam

** NOTE: NOTE: Medications under undergoing going Phase II hepatic metabolism are generally preferred in the elderly due to inactive metabolites (no accumulation)

 

Other Factors Affecting Drug Metabolism •

Gender

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Comorbid conditions

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Smoking Diet

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Drug interactions interactions

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Race Frailty(kelemahan)

 

Concepts in Drug Elimination Elimination •

Half-life  –

time for serum concentration of drug to decline by 50% (expressed in hours)

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Clearance  –

volume of serum from which the drug is removed per unit of time (mL/min or L/hr)

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Reduced elimination  drug accumulation and toxicity toxicity

 

Effects of Aging on the Kidney •

Decreased kidney size

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Decreased renal blood flow

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Decreased number of functional nephrons Decreased tubular secretion

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Result:  glomerular filtration filtration rate (GFR)

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Decreased drug clearance: atenolol, gabapentin, H2 blockers, blocker s, digoxin, allopurinol, quinolones quinolones  

 

Estimating Estima ting GFR in the Elderly •

•

Creatinine clearance (CrCl) is used to estimate glomerular rat rate e Serum creatinine alone not accurate accurate in the e elderly lderly  –

   lean body mass  lower creatinine production

 –

rate e    glomerular filtration rat

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Serum stays in normal range, masking changecreatinine in creatinine clearance

 

Determining Creatinine Clearance •

Measure  –

 –

•

Time consuming Requires 24 hr urine collection

Estimate  –

Cockroft Gault equation

(IBW in kg) x (140-age) -----------------------------72 x (Scr in mg/dL)

x (0.85 for females)

 

Example: Creatinine Clearance vs. Age in a 55 kg Woman  Age

Scr

CrCl

30

1.1

65

50

1.1

53

70

1.1

41

90

1.1

30

 

 

 

 

 

Pharmacodynamics (PD) •

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Definition: the time course and intensity of pharmacologic effect of a drug Age-related Age-relat ed changes:  –

 –

   sensitivity to sedation and psychomotor impairment(perusakan) with benzodiazepines    level and duration of pain relief with narcotic agents

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   drowsiness and lateral sway with alcohol    HR response to beta-blockers

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   sensitivity to anti-cholinergic agents

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   cardiac sensitivity to digoxin

 –

 

PK and PD Summary •

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PK and PD changes generally rresult esult in decreased clearance and increased sensitivity to medications in older adults Use of lower doses, longer intervals, slower titration are helpful helpful in decreasing d ecreasing the risk of drug intolerance and to toxicity xicity Careful monitoring is necessary to ensure successful outcomes

 

Optimal Pharmacotherapy Pharmacotherapy •

Balance between overprescribing and underprescribing  –

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 –

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Correct drug Correct dose Targets appropriate condition Is appropriate for the patient

Avoid “a pill for every ill” 

Alwayss consider non-pharmacologic therapy Alway

 

Consequences of Overpr Overprescribing escribing •

Adverse Adver se drug events (ADEs)

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Drug interactions interactions

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Duplication of drug therapy

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Decreased quality of life life

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Unnecessary cost Medication non-adherence

 

Adverse Drug Events (ADEs) •

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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

 

Most Common Medications Associated with ADEs in the Elderly •

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Opioid analgesics NSAIDs Anticholinergics Benzodiazepines Also: cardiovascular agents, CNS agents, and musculoskeletal musculosk eletal agents

Adverse Drug Reaction Reaction Risk Factors in Older Outpatients. Am J Ger Pharmacotherapy 2003;1(2):82-89.

 

The Beers Criteria High Potential for

High Potential for

Severe ADE

Less Severe ADE

amitriptyline

antihistamines

chlorpropamide digoxin >0.125mg/d disopyramide GI antispasmodics

diphenhydramine dipyridamole ergot mesyloids indomethacin

meperidine methyldopa pentazocine ticlopidine

muscle relaxants

 

Patient Risk Factors for ADEs for ADEs •

Polypharmacy

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Multiple co-morbid conditions

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Prior adverse drug event

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Low body weight or body mass index

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Age > 85 years Estimated Estimat ed CrCl