OBAT PADA MANULAOBAT PADA MANULA

Noor WijayahadiNoor WijayahadiApril 2007April 2007

Medications Most Commonly Used Medications Most Commonly Used in the Communityin the Community

AnalgesicsAnalgesics

DiureticsDiuretics

CardiovascularCardiovascular

Sedative-hypnoticsSedative-hypnotics

Medications Most Commonly Used Medications Most Commonly Used in the Nursing Homein the Nursing Home

AntipsychoticsAntipsychotics

Sedative-hypnoticsSedative-hypnotics

DiureticsDiuretics

AntihypertensivesAntihypertensives

AnalgesicsAnalgesics

CardiovascularCardiovascular

AntibioticsAntibiotics

Manula Manula Resiko tinggi mengalami Resiko tinggi mengalami efek merugikan dari obatefek merugikan dari obat

Faktor penderitaFaktor penderita– Age-associated changes in Age-associated changes in pharmacokineticspharmacokinetics– Age-associated changes in Age-associated changes in pharmacodynamicspharmacodynamics– ComorbidityComorbidity: drug-disease interactions: drug-disease interactions– PolypharmacyPolypharmacy: drug-drug interactions: drug-drug interactions– Kemampuan homeostasis berkurangKemampuan homeostasis berkurang– Fungsi organ berkurangFungsi organ berkurang

Faktor sistem layanan medikFaktor sistem layanan medik– Fragmentation of care (Poly-doctoring)Fragmentation of care (Poly-doctoring)– Inadequate training in principles of geriatric practiceInadequate training in principles of geriatric practice

Therapeutic Response

Toxic Response

Therapeutic Window

Age

Increasing Age

“The Precipice”

PhysiologicReservesAvailable

PhysiologicReserves

Already In Use

Masalah UtamaMasalah Utama

Pilihan obat atau dosis yang tidak tepatPilihan obat atau dosis yang tidak tepat

Concomitant disease Concomitant disease affect metabolism affect metabolism of or response to drugof or response to drug

Polypharmacy Polypharmacy drug - drug interactions drug - drug interactions

Patient behavioural factorsPatient behavioural factors

Perubahan PHARMACOKINETICSPerubahan PHARMACOKINETICS

AbsorptionAbsorptionactive transferactive transfer

Body compositionBody compositionlean body masslean body mass

body fatbody fat

plasma albuminplasma albumin

Liver metabolismLiver metabolismoxidation / microsomal enzymesoxidation / microsomal enzymes

Renal clearanceRenal clearance

Perubahan Perubahan PHARMACODYNAMICSPHARMACODYNAMICS

Brain sensitivity Brain sensitivity Benzodiazepines and Benzodiazepines and

narcotic analgesics more effectivenarcotic analgesics more effective

Coagulation mechanism control Coagulation mechanism control

Anticoagulants more potentAnticoagulants more potent

Adrenergic receptor sensitivity Adrenergic receptor sensitivity

B-blockers less effectiveB-blockers less effective

Penurunan fungsi homeostasisPenurunan fungsi homeostasis

Baroreceptor sensitivityBaroreceptor sensitivitypostural hypotensionpostural hypotension

ThermoregulationThermoregulationhypothermiahypothermia

COMMON PITFALLS 1 :COMMON PITFALLS 1 :Gagal mengobati kondisi yang seharusnya Gagal mengobati kondisi yang seharusnya

bisa diobati (treatable conditions)bisa diobati (treatable conditions)

Thrombolytic therapyThrombolytic therapythe older the patient, the greater the benefitthe older the patient, the greater the benefit

the older the patient, the less likely to be the older the patient, the less likely to be thrombolysedthrombolysed

HypertensionHypertension30 - 40% decrease in risk of CVA if ISH treated30 - 40% decrease in risk of CVA if ISH treated

BLOOD PRESSURE AND AGEBLOOD PRESSURE AND AGE

0

20

40

60

80

100

120

140

160

30 40 50 60 70 80

COMMON PITFALLS 2 :COMMON PITFALLS 2 :

Prescribing for symptom and not for Prescribing for symptom and not for

diagnosisdiagnosis

“ A pill for every ill ”

NEW HYPNOTIC PRESCRIPTIONSNEW HYPNOTIC PRESCRIPTIONS(per percentage patient pop. per yr.)(per percentage patient pop. per yr.)

1987 19890

1

2

3

4

5

6

1987 1989

Male 0-65

Female 0-65

Male >65

Female >65

PRESCRIPTIONS BY AGEPRESCRIPTIONS BY AGE(Items per person per year)(Items per person per year)

42 46 50 54 58 62 66 70 74 78 82 86 900

5

10

15

20

25

30

35

40

42 46 50 54 58 62 66 70 74 78 82 86 90

EFFECTIVE PRESCRIBING 1EFFECTIVE PRESCRIBING 1

Utamakan non-pharmalogical treatmentUtamakan non-pharmalogical treatmentmodify dietmodify diet

stop smoking, reduce alcoholstop smoking, reduce alcohol

physical exercisephysical exercise

walking aids, household adaptationswalking aids, household adaptations

social supportssocial supports

EFFECTIVE PRESCRIBING 2EFFECTIVE PRESCRIBING 2

Treat conditions in order of Treat conditions in order of prioritypriorityPertimbangkan Pertimbangkan kegagalan fungsi organkegagalan fungsi organStart low Start low mulai dosis kecil mulai dosis kecil , naikkan , naikkan dengan hati-hatidengan hati-hatiGunakan Gunakan formulariumformularium yang terbatas yang terbatasMonitor Monitor compliance and responsecompliance and responseReviewReview pemakaian obat secara reguler pemakaian obat secara regulerIkut sertakan PENDERITAIkut sertakan PENDERITA

Who Takes the Most Medications?Who Takes the Most Medications?

WomenWomen

Individuals with Individuals with multiple health multiple health conditionsconditions

Frail elderlyFrail elderly

Nursing home Nursing home residentsresidents

Medications Most Commonly Used Medications Most Commonly Used in the Communityin the Community

AnalgesicsAnalgesics

DiureticsDiuretics

CardiovascularCardiovascular

Sedative-hypnoticsSedative-hypnotics

Umur mempengaruhi Umur mempengaruhi metabolisme obat?metabolisme obat?

Pada manula:Pada manula:– Slower organ functionSlower organ function– Slower blood circulationSlower blood circulation– Increased body fat Increased body fat

obat bertahan lama di dalam tubuh obat bertahan lama di dalam tubuh resiko terkena efek samping obat resiko terkena efek samping obat meningkatmeningkat

Age-Related Changes: Age-Related Changes:

Total body water menurun Total body water menurun konsentrasi dalam konsentrasi dalam darah obat yang larut-air meningkatdarah obat yang larut-air meningkat

Perubahan berat badan Perubahan berat badan mempengaruhi dosis mempengaruhi dosis yang diperlukan dan lama obat dalam tubuh: yang diperlukan dan lama obat dalam tubuh: – More body fat More body fat prolonged half-life prolonged half-life – Less lean body mass Less lean body mass increased drug concentration increased drug concentration

Perubahan sistem pencernaan Perubahan sistem pencernaan mempengaruhi kecepatan absorbsi obat mempengaruhi kecepatan absorbsi obat onset obat lebih lamaonset obat lebih lama

Age-Related Changes: Age-Related Changes:

Slower circulation Slower circulation delay drugs getting to delay drugs getting to liver and kidneysliver and kidneys

Slow down of liver and kidneys Slow down of liver and kidneys affects affects time it takes for medication to break down time it takes for medication to break down and leave body and leave body

Less absorption from transdermal patchesLess absorption from transdermal patches

Drug “receptor” sites may be different in Drug “receptor” sites may be different in older adults older adults

Changes in PharmacokineticsChanges in Pharmacokinetics

Perubahan fisiologis dan fungsi organ pada Perubahan fisiologis dan fungsi organ pada manula manula perubahan Farmakokinetik perubahan Farmakokinetik

Pharmacokinetics is the time course of a drug Pharmacokinetics is the time course of a drug and its metabolites through the body and its metabolites through the body

– AbsorptionAbsorption

– Distribution Distribution

– Clearance: elimination (renal), metabolism (liver) Clearance: elimination (renal), metabolism (liver)

2004: Cusack, Amer. J of Geriatric Pharmacotherapy 2004: Cusack, Amer. J of Geriatric Pharmacotherapy

Volume of Distribution (Vd)Volume of Distribution (Vd)

Proporsi lemak meningkat dan volume otot Proporsi lemak meningkat dan volume otot berkurang berkurang merubah Vd merubah Vd

Vd obat larut lemak (Vd obat larut lemak (fat soluble drugfat soluble drug) ) meningkat meningkat waktu paro meningkat: waktu paro meningkat: diazepam,diazepam, thiopental, trazadonethiopental, trazadone

Vd obat larut air (Vd obat larut air (water soluble drugwater soluble drug) ) menurun menurun kadar obat dalam plasma kadar obat dalam plasma meningkat: meningkat: ethanol, lithium, ethanol, lithium, aminoglycosides, alcohol, digoxinaminoglycosides, alcohol, digoxin

Protein BindingProtein Binding

albumin berkurang albumin berkurang chronic disease: chronic disease: e.g.,malnutrition, liver or kidney conditions.e.g.,malnutrition, liver or kidney conditions.

obat dengan ikatan protein tinggi obat dengan ikatan protein tinggi kadar kadar obat bebas meningkat.obat bebas meningkat.

ceftriaxone,diazepam, phenytoin, ceftriaxone,diazepam, phenytoin, warfarin.warfarin.

Eliminasi Obat menurunEliminasi Obat menurun

Fungsi ginjal menurun Fungsi ginjal menurun eliminasi oleh ginjal eliminasi oleh ginjal berkurang.berkurang.Even in the absence of kidney disease renal clearance Even in the absence of kidney disease renal clearance may be reduced 35-50%.may be reduced 35-50%. therapeutic effect dan resiko toksisitas meningkattherapeutic effect dan resiko toksisitas meningkat perlu pengurangan dosis atau perubahan interval perlu pengurangan dosis atau perubahan interval pemberian obat.pemberian obat.

Metabolisme hepar berkurangMetabolisme hepar berkurang

•Phase I, terutama reaksi oksidatif menurun

•Phase II, terutama reaksi konjugasi relatif tidak berubah.

diazepam is metabolized via Phase I reactions in the liver, at least initially.

Drugs with Cytochrome P450 EffectsDrugs with Cytochrome P450 Effects(partial)(partial)

Inhibitors Inducers

Allopurinol Metronidazole Barbiturates

Amiodorone Quinolones Carbamazepine

Azole antifungals Phenytoin

Cimetidine Rifampin

INH Tobacco

SSRIs

Tacrine

Hepatic MetabolismHepatic Metabolism

Decreased liver size and hepatic blood flow.Decreased liver size and hepatic blood flow.Regional blood flow to the liver at age 65 is Regional blood flow to the liver at age 65 is reduce by 40-45% compared to a 25 year old.reduce by 40-45% compared to a 25 year old.Metabolic clearance of drugs by the liver may be Metabolic clearance of drugs by the liver may be reduced.reduced.Disease effects: liver congestion from heart Disease effects: liver congestion from heart failure decreases warfarin metabolism and an failure decreases warfarin metabolism and an increased pharmacologic response.increased pharmacologic response.Environmental effects: smoking stimulates Environmental effects: smoking stimulates monoxygenase enzymes and increases monoxygenase enzymes and increases clearance of theophylline. clearance of theophylline.

Changes in PharmacodynamicsChanges in Pharmacodynamics

Older patients may have more sedation and Older patients may have more sedation and impaired function after a single dose of impaired function after a single dose of benzodiazepines than younger persons. benzodiazepines than younger persons.

After single dose of nitrazepam older patients After single dose of nitrazepam older patients made more mistakes on psychomotor testing made more mistakes on psychomotor testing compared to placebo while younger patients compared to placebo while younger patients had no impairment .had no impairment .

Suboptimal Quality Suboptimal Quality

Typology of Quality Problems:Typology of Quality Problems:– Overuse (Polypharmacy)Overuse (Polypharmacy)– UnderuseUnderuse– Misuse (Inappropriate Prescribing)Misuse (Inappropriate Prescribing)– ErrorsErrors

Suboptimal PrescribingSuboptimal Prescribing

PolypharmacyPolypharmacy

Underuse of Effective MedicationsUnderuse of Effective Medications

Drug-Drug InteractionsDrug-Drug Interactions

Drug-Disease InteractionsDrug-Disease Interactions

Inadequate MonitoringInadequate Monitoring

Inappropriate DosingInappropriate Dosing

Inappropriate DurationInappropriate Duration

Drugs to AvoidDrugs to Avoid

Drug-Drug InteractionsDrug-Drug InteractionsPenyebab tersering ESO pada manulaPenyebab tersering ESO pada manulaJumlahnya sangat banyak Jumlahnya sangat banyak Almost Almost countless countless peresepan elektronik peresepan elektronik Some common examplesSome common examples– Statins and erythromycin and other antibioticsStatins and erythromycin and other antibiotics– TCAs and clonidine or type 1Anti-arrythmicsTCAs and clonidine or type 1Anti-arrythmics– Warfarin and multiple drugs Warfarin and multiple drugs – ACE inhibitors increase hypoglycemic effect of ACE inhibitors increase hypoglycemic effect of

sulfonylureassulfonylureas

Drug-disease InteractionsDrug-disease Interactions

Patient with PD have increased risk of drug Patient with PD have increased risk of drug induced confusioninduced confusionNSAIA (and COX-2’s) s can exacerbate CHFNSAIA (and COX-2’s) s can exacerbate CHFUrinary retention in BPH patients on Urinary retention in BPH patients on decongestants or anticholinergicsdecongestants or anticholinergicsConstipation worsened by calcium, Constipation worsened by calcium, ahticholinergics, calcium channel blockersahticholinergics, calcium channel blockersNeuroleptics and quinolones lower seizure Neuroleptics and quinolones lower seizure thresholdsthresholds

PolypharmacyPolypharmacy

Polypharmacy = pemberian banyak Polypharmacy = pemberian banyak obat melebihi indikasi penggunaanobat melebihi indikasi penggunaan

59% manula mendapat obat tanpa 59% manula mendapat obat tanpa indikasi yang jelas.indikasi yang jelas.

55% manula mendapat obat 55% manula mendapat obat tanpa tanpa indikasiindikasi, 32.7% mendapat , 32.7% mendapat obat yang obat yang tidak efektiftidak efektif, 16.8% mendapat , 16.8% mendapat obat obat duplikasiduplikasi2001: Hanlon, JAGS2001: Hanlon, JAGS

UnderuseUnderuse

Among patients elderly patients with Among patients elderly patients with cardiovascular disease and diabetes, only cardiovascular disease and diabetes, only 19.1% of patients were prescribed statins. In 19.1% of patients were prescribed statins. In patients 66 to 74 years old, the adjusted patients 66 to 74 years old, the adjusted probabilities of statin prescription were 37.7%, probabilities of statin prescription were 37.7%, 26.7%, and 23.4% in the categories of low, 26.7%, and 23.4% in the categories of low, intermediate, and high baseline risk, intermediate, and high baseline risk, respectively. respectively.

The likelihood of statin prescription was 6.4% The likelihood of statin prescription was 6.4% lower (adjusted odds ratio, 0.94; 95% lower (adjusted odds ratio, 0.94; 95% confidence interval, 0.93-0.95) for each year of confidence interval, 0.93-0.95) for each year of increase in age and each 1% increase in increase in age and each 1% increase in predicted 3-year mortality risk.predicted 3-year mortality risk.2004: Ko, JAMA2004: Ko, JAMA

Inappropriate Prescribing Inappropriate Prescribing

20-27% manula mendapat resep yang 20-27% manula mendapat resep yang tidak diperlukan (inappropriate). tidak diperlukan (inappropriate).

Inappropriate prescribing meningkatkan Inappropriate prescribing meningkatkan resiko jatuh, fraktur femur, cognitive resiko jatuh, fraktur femur, cognitive impairment, diminished independence, impairment, diminished independence, dan mortalitasdan mortalitas

inappropriate drug prescribing to inappropriate drug prescribing to the elderly?the elderly?

The Beers ListThe Beers List.

a list of medications identified by an expert panel as being inappropriate for older persons because of ineffectiveness or because they pose a high risk for adverse drug events.

Beers MH Arch Intern Med 1997

The Beers ListThe Beers List

The Beers List, berisi 33 obat dalam The Beers List, berisi 33 obat dalam 3 kategori:3 kategori:

3. Drugs with some indications, but that are often misused.

2. Drugs that are rarely appropriate.

1. Drugs that should always be avoided.

Zhan et al. JAMA 2001

Drugs And Dosages to AvoidDrugs And Dosages to Avoid

MeperidineMeperidine

DiphenhydramineDiphenhydramine

The most anticholinergic tricyclics: The most anticholinergic tricyclics: amitryptiline, doxepin, imipramine amitryptiline, doxepin, imipramine

Long acting benzodiazepines such as Long acting benzodiazepines such as diazepamdiazepam

Long acting NSAIDs such as piroxicamLong acting NSAIDs such as piroxicam

High dose thiazides (>25mg)High dose thiazides (>25mg)

Iron: 325 mg once daily is enoughIron: 325 mg once daily is enough

11 drugs that should always be 11 drugs that should always be avoided in the elderly:avoided in the elderly:

BarbituratesBarbiturates

ChlorpropamideChlorpropamide

FlurazepamFlurazepam

MeperidineMeperidine

MeprobamateMeprobamate

PentazocinePentazocine

Belladonna alkaloidsBelladonna alkaloids

DicyclomineDicyclomine

HyoscyamineHyoscyamine

PropanthelinePropantheline

TrimethobenzamideTrimethobenzamide

Zhan et al. JAMA 2001

Tangga Peresepan Tangga Peresepan (Prescribing Cascade)(Prescribing Cascade)

The prescribing cascade terjadi bila satu obat diresepkan,

Menyebabkan timbulnya efek samping obat / adverse drug event (ADE),

Mendorong peresepan obat kedua untuk mengatasi ESO sebelumnya

Drug 1

Drug 2

ADE

Rochon PA et al, BMJ 1997

The Prescribing CascadeThe Prescribing Cascade

Metoclopramide

Extrapyramidal Effects

Levodopa Rx

There are numerous examples of the prescribing cascade in the medical literature.

For example, it has been observed that patients prescribed metoclopramide ( a gastric motility agent) are more likely to be initiated on treatments generally reserved for the management of idiopathic Parkinson’s Disease (e.g. Drugs containing Levodopa).

In this case, metoclopramide use can lead to extrapyramidal symptoms, which may be misdiagnosed as Parkinson’s Disease.

Avorn J et al, JAMA 1995

NSAID Rx

Antihypertensive Rx

Blood Pressure

The Prescribing CascadeThe Prescribing CascadeAnother example relates to the fact that older persons who have been prescribed NSAIDs appear to be at increased risk for being initiated on antihypertensive therapy.

In this case, NSAID use increases blood pressure leading to the need for blood pressure lowering therapy.

In both examples, the initiation of new drug treatments in older persons could have been avoided if there was recognition of the risks of certain drug treatments (e.g. metoclopramide and NSAIDs) in elderly patients.

Gurwitz JH et al, JAMA 1994

The “Prescribing Cascade”The “Prescribing Cascade”

Penyebab utama polypharmacy pada Penyebab utama polypharmacy pada manulamanula Some common examplesSome common examples– NSAID ->HTN->antihypertensive therapyNSAID ->HTN->antihypertensive therapy– Metoclopromide ->Parkinsonism ->SinemetMetoclopromide ->Parkinsonism ->Sinemet– Dihydropyridine -> edema ->furosemideDihydropyridine -> edema ->furosemide– NSAIA ->H2 blocker ->delirium ->haldolNSAIA ->H2 blocker ->delirium ->haldol– HCTZ ->gout->NSAIA ->2nd antihypertensiveHCTZ ->gout->NSAIA ->2nd antihypertensive– Sudafed ->urinary retention ->alpha blockerSudafed ->urinary retention ->alpha blocker– Antipsychotic ->akithesia ->more medsAntipsychotic ->akithesia ->more meds

NSAID (Anti-inflamasi non-steroid)NSAID (Anti-inflamasi non-steroid)

Efektifitas Parasetamol = NSAIDs pada Efektifitas Parasetamol = NSAIDs pada osteoartritis ringanosteoartritis ringan

NSAIDs side effectsNSAIDs side effects

– GI hemorrhageGI hemorrhage

– Decline in GFR Decline in GFR

Decreased effectiveness of diuretics, anti-Decreased effectiveness of diuretics, anti-hypertensive agentshypertensive agents

Indication should justify the increased Indication should justify the increased toxicity of NSAIDstoxicity of NSAIDs

Drugs and Cognitive ImpairmentDrugs and Cognitive Impairment

Anticholinergic drugs are common Anticholinergic drugs are common offenders (TCAs, benadryl and other offenders (TCAs, benadryl and other antihistamines, many others)antihistamines, many others)Other offenders cimetidine, steroids, Other offenders cimetidine, steroids, NSAIAs NSAIAs Medical Letter 2000 Drug Safety 1999 Drugs and Aging 1999 Medical Letter 2000 Drug Safety 1999 Drugs and Aging 1999

Drugs and FallsDrugs and Falls

Biggest risk drugs are long acting benzodiazepines Biggest risk drugs are long acting benzodiazepines and other sedative-hypnoticsand other sedative-hypnoticsBoth SSRIs and TCAs associated with increased Both SSRIs and TCAs associated with increased risk of fallingrisk of fallingBeta blockers NOT associated with increased risk Beta blockers NOT associated with increased risk of falling in published literatureof falling in published literatureMild increase in fall risk from diuretics, type 1A Mild increase in fall risk from diuretics, type 1A anti-arrythmics, and digoxinanti-arrythmics, and digoxinLeipzig, JAGSLeipzig, JAGS

Drug-Food InteractionsDrug-Food Interactions

Interactions between drugs and foodInteractions between drugs and food– warfarin and Vitamin K containing foods warfarin and Vitamin K containing foods

(remember green tea, as well)(remember green tea, as well)– Phenytoin & vitamin D metabolismPhenytoin & vitamin D metabolism– Methotrexate and folate metabolismMethotrexate and folate metabolism

Drug impact on appetiteDrug impact on appetite– Digoxin may cause anorexiaDigoxin may cause anorexia– ACE inhibitors may alter tasteACE inhibitors may alter taste

Anticipate Side EffectAnticipate Side EffectNarcoticsNarcotics– Begin lactulose or sorbitol and a stimulant laxativeBegin lactulose or sorbitol and a stimulant laxative– Colace is NOT sufficient in most instancesColace is NOT sufficient in most instances

SteroidsSteroids– Think about osteoporosis preventionThink about osteoporosis prevention– Remember steroid induced diabetesRemember steroid induced diabetes

LevothyroxineLevothyroxine– Calcium interferes with absorption of Calcium interferes with absorption of

levothyroxinelevothyroxine

Drug DiscrepanciesDrug Discrepancies

Difference between medical record and Difference between medical record and medication bottles in 76% of casesmedication bottles in 76% of cases– 51% of time medication not recorded51% of time medication not recorded– 29% medication recorded that patient not 29% medication recorded that patient not

takingtaking– 20% dosage discrepancy20% dosage discrepancy

Risk Factors: Age, number of medicationsRisk Factors: Age, number of medications– Bedell et al Arch Intern Med 160, 2000Bedell et al Arch Intern Med 160, 2000

High Risk SituationsHigh Risk Situations

Patient seeing multiple providersPatient seeing multiple providers

Patient on multiple drugsPatient on multiple drugs

Patient lives alone and/or has Patient lives alone and/or has cognitive impairmentcognitive impairment

Discharge from hospital or any Discharge from hospital or any change in venuechange in venue

Hospitalization: A High Risk TimeHospitalization: A High Risk Time

At hospitalization:At hospitalization:

40% of admission medications stopped40% of admission medications stopped

45% of discharge medications were started45% of discharge medications were started

Serious prescribing problems in 22%Serious prescribing problems in 22%

Other prescribing problems in 66%Other prescribing problems in 66%– Beers JAGS 1989, Lipton Medical Care 1992Beers JAGS 1989, Lipton Medical Care 1992

NonadherenceNonadherence

Lack of understanding of how to takeLack of understanding of how to take– High risk times: Hospital discharge, new meds High risk times: Hospital discharge, new meds

added, complex regimensadded, complex regimens

Unable to takeUnable to take

Conscious nonadherenceConscious nonadherence– Side effectsSide effects– Lack of understanding of benefits of drugLack of understanding of benefits of drug– FinancialFinancial

Complementary TherapiesComplementary Therapies

Very commonly used in the elderlyVery commonly used in the elderly

Some common herbs and alternative therapies:Some common herbs and alternative therapies:– ““Anti-aging”Anti-aging” DHEA, growth hormoneDHEA, growth hormone– DementiaDementia Gingko bilobaGingko biloba– BPHBPH Saw palmetto, PC-SPESSaw palmetto, PC-SPES– OAOA Chondroiton sulfate, Chondroiton sulfate,

glucosamine glucosamine – DepressionDepression St. John’s wort, SAMeSt. John’s wort, SAMe

Adulterants in ProductsAdulterants in ProductsCalifornia Department of Health California Department of Health Services, Food and Drug BranchServices, Food and Drug Branch– screened 250 Asian herbal productsscreened 250 Asian herbal products– collected from herbal stores in Californiacollected from herbal stores in California– assayed products using gas chromatography, assayed products using gas chromatography,

mass spectrometry, and atomic-absorption mass spectrometry, and atomic-absorption techniquestechniques

– Ko, NEJM 1998; 339; 847Ko, NEJM 1998; 339; 847

32% contained unlabeled medications, 32% contained unlabeled medications, 14% mercury, 14% arsenic, 10% lead14% mercury, 14% arsenic, 10% lead

Herbals and Supplements: Herbals and Supplements: RegulationRegulation

Demonstration of safety is NOT required prior to Demonstration of safety is NOT required prior to marketingmarketing

Manufacturing standards are not requiredManufacturing standards are not required

Can have Can have health health claims, but not claims about claims, but not claims about treating, preventing, or curingtreating, preventing, or curing

For glucosamine/chondroitin, on third of For glucosamine/chondroitin, on third of combinations did not contain listed ingredientcombinations did not contain listed ingredient

www.consumerlabs.com has some drug www.consumerlabs.com has some drug informationinformation

Herbals and Supplements:Potential Herbals and Supplements:Potential interactions with Rx Drugsinteractions with Rx Drugs

SAMe may increase homocysteine SAMe may increase homocysteine levelslevels

St. John’s wort and Oral contraceptivesSt. John’s wort and Oral contraceptives

Ginkgo may increase anticoagulant Ginkgo may increase anticoagulant effects of ASA, warfarin, NSAIAs, effects of ASA, warfarin, NSAIAs, ticlopidine, and may interact with ticlopidine, and may interact with MAOIsMAOIs

Bottom line: Try to know what your Bottom line: Try to know what your patient is taking, and ask in a patient is taking, and ask in a nonjudgmental waynonjudgmental way

Prinsip Manajemen ObatPrinsip Manajemen Obat

Riwayat pemakaian obat yang lengkap, Riwayat pemakaian obat yang lengkap, termasuk obat herba/tradisional/obat bebastermasuk obat herba/tradisional/obat bebasHindari pemberian obat bila Hindari pemberian obat bila keuntungan/benefit kecil , atau ada alternatif keuntungan/benefit kecil , atau ada alternatif pengobatan non-farmakologis pengobatan non-farmakologis Pertimbangkan hargaPertimbangkan hargaStart low, go slow, but get there!Start low, go slow, but get there!Buat cara pemberian yang sederhanaBuat cara pemberian yang sederhanaTulis cara pemakaian sejelas mungkinTulis cara pemakaian sejelas mungkinMinta penderita membawa seluruh obat yang Minta penderita membawa seluruh obat yang sedang diminum setiap kali periksasedang diminum setiap kali periksa

Principles (continued)Principles (continued)Pertimbangkan pemakaian kotak obat harian Pertimbangkan pemakaian kotak obat harian atau “mediset”atau “mediset”

Hentikan pemakaian obat yang tidak jelas Hentikan pemakaian obat yang tidak jelas keuntungannya atau resiko efek sampingnya keuntungannya atau resiko efek sampingnya lebih merugikanlebih merugikan

Hati-hati pemakaian obat baru (newer drugs)Hati-hati pemakaian obat baru (newer drugs)

Hindari penggunaan obat > 5 macam Hindari penggunaan obat > 5 macam Consider if the benefit of the 7th or 8th drug is Consider if the benefit of the 7th or 8th drug is sufficient to justify the cost, increase in sufficient to justify the cost, increase in complexity of regimen, and risk of side effectscomplexity of regimen, and risk of side effects

Newer drugsNewer drugs

What is unique about this compound?What is unique about this compound?

What clinical data is available?What clinical data is available?

How does it compare with traditional How does it compare with traditional therapy?therapy?

How expensive is it?How expensive is it?

With third party payers cover this With third party payers cover this product?product?

Does the potential advantage of this new Does the potential advantage of this new drug justify the risk of using a new drug?drug justify the risk of using a new drug?

The Message for TodayThe Message for Today

Start lowStart low

Go slow (but get to therapeutic levels)Go slow (but get to therapeutic levels)

Sometimes say no (how about other non-Sometimes say no (how about other non-drug treatments?)drug treatments?)