fmk6. rational drug use
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PENGGUNAAN OBATPENGGUNAAN OBATSECARA RASIONALSECARA RASIONAL
(Rational Drug Use)(Rational Drug Use)
NafrialdiNafrialdi
Departemen Farmakologi FKUIDepartemen Farmakologi FKUI
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Rational Drug UseRational Drug Use
Herophilus 300 B.CHerophilus 300 B.C (from Alexandria):(from Alexandria):Medicines are nothing in themselvesMedicines are nothing in themselves
but are the very hands of God ifbut are the very hands of God ifemployed with reason & prudence.employed with reason & prudence.
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Definition of RDUDefinition of RDU
The rational use of drugs requires that:The rational use of drugs requires that: patients receive medications appropriate topatients receive medications appropriate to
their clinical needstheir clinical needs
in doses that meet their own individualin doses that meet their own individualrequirements,requirements, for an adequate period of time, andfor an adequate period of time, and at the lowest cost to them and theirat the lowest cost to them and their
community.community.
WHO conference of experts, Nairobi 1985WHO conference of experts, Nairobi 1985
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Irrational Drugs UseIrrational Drugs Use
The use of drugs without clear indicationThe use of drugs without clear indication The use of wrong drugs for a specific conditionThe use of wrong drugs for a specific condition
requiring drug therapyrequiring drug therapy
The use of drugs with doubtful or unprovenThe use of drugs with doubtful or unprovenefficacyefficacy
The use of drugs of uncertain safety statusThe use of drugs of uncertain safety status Failure to prescribe available, safe, & effectiveFailure to prescribe available, safe, & effective
drugsdrugs Incorrect administration, dosages, or durationIncorrect administration, dosages, or duration
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THERE IS NO CLEAR CUT BETWEENTHERE IS NO CLEAR CUT BETWEEN
RATIONAL AND IRRATIONALRATIONAL AND IRRATIONAL
IR
RA
TION
AL
RATI
ONAL
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Types of Irrational DrugTypes of Irrational Drug
UseUse
Incorrect prescribingIncorrect prescribing
Over-prescribingOver-prescribing (dose, duration)(dose, duration)
Under-prescribingUnder-prescribing
Extravagant prescribingExtravagant prescribing (unnecessary drugs)(unnecessary drugs)
Multiple prescribingMultiple prescribing
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Impact of InappropriateImpact of Inappropriate
Use of DrugsUse of Drugs
Reduced
quality of
therapy
morbiditymortality
Waste of
resources
Risk of
unwanted
effects
patients rely on
unnecessary drugs
Psycho-social
impacts
reduced availabilityincreased cost
adverse reactions
bacterial resistance
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Factors Underlying IrrationalFactors Underlying Irrational
Drug UseDrug Use
inefficient
management non-availability
of required
drugs
Drug SupplyDrug SupplyDrug SupplyDrug Supply
availability of
unsafe drugs informal
prescribers etc.
Drug RegulationDrug RegulationDrug RegulationDrug Regulation
promotion misleading
claims
IndustryIndustryIndustryIndustry
Diagnosisuncertainty
lack of education,training and druginformation
heavy patient load
pressure to
prescribe generalization of
limited beliefs
misleading beliefsabout efficacy
PrescribersPrescribersPrescribersPrescribers
drug
misinformation
misleading
beliefs
inability to
communicate
problems
PatientsPatientsPatientsPatients
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RATIONAL THERAPEUTIC MANEUVERRATIONAL THERAPEUTIC MANEUVER
1. Define patients diagnosis
2. Define therapeutic goals: causal,
symptomatic, paliative, supportive3. Chose therapeutic option: non
pharmacologic, pharmacologic, surgical
4. Information/instruction5. Start treatment
6. Monitor therapeutic outcome
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1. Define Patients Diagnosis1. Define Patients Diagnosis
Anamnesis
Physical examinations
Advance examinations
Laboratory
Radiology
Histopathology, etc
Diagnosis Be selective
Do not rely on laboratory test olone for D/
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2. Define Therapeutic Goal2. Define Therapeutic Goal
Causal, symptomatic, paliative, supportive? Does the patient really need the drug ?
Are you quite sure that drug will help ? Or, just to fulfill the security feeling of doctor ?
Or, just to fulfill the subjective of patients ?
Is there financial/commercial interest ?
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Chose appropriate drug based on the
following criteria:
Efficacy
Safety
Suitability
Affordability ( cost)
Write a clear and readable prescription
3. Chose Therapeutic Option3. Chose Therapeutic Option
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4. Give Clear Information and Instruction4. Give Clear Information and Instruction
To assure patients adherence
(compliance)
To create a good doctor-patientrelationship
Clear instruction on:
Drug administration Timing of adm. (before/after meal)
Possible adverse effects
Next consultation
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5. Start Treatment5. Start Treatment
Verify the appropriateness of drugs
Indication, doses, duration
Efficacy
Safety
Suitability
Affordability ( cost)
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Is therapeutic goals obtained ?
Under treatment ?
Over treatment ? When to stop treament ?
6. Monitor the Outcome/ Evaluation6. Monitor the Outcome/ Evaluation
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Some Important IssuesSome Important Issues
Antibiotic misuseAntibiotic misuse
Antibiotic combinationAntibiotic combination
PolypharmacyPolypharmacy
Drug-drug InteractionDrug-drug Interaction
16
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AntibioticAntibiotic MMisuseisuse
Antimicrobial agents areAntimicrobial agents are the most commonlythe most commonlyused and misusedused and misused of all drugs.of all drugs.
The inevitable consequenceThe inevitable consequence :: emergence ofemergence of
antibiotic-resistantantibiotic-resistant pathogens.pathogens. Overprescribing remains widespreadOverprescribing remains widespread due todue to
diagnostic uncertaintydiagnostic uncertainty,, patient demandpatient demand,, andandtime pressure on cliniciantime pressure on clinician
Reducing inappropriate antibiotic use is thoughtReducing inappropriate antibiotic use is thoughtto be best way to control resistance..to be best way to control resistance..
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Antibiotic in viral infections(exp. DHF).
Therapy offever of unknown origin
masking underlying infection, delay the diagnosis,
rendering culture negative. Drug combinations or broadest spectra as a
cover for diagnostic imprecision.
In the absence of clear indication, antibioticoften may be used if disease is severe or life-
threatening
Some AntibioticSome Antibiotic MMisusesisuses
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The first consideration inThe first consideration in
selecting antimicrobial isselecting antimicrobial is
whether it is even indicated.whether it is even indicated.
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Selection of AntibioticsSelection of Antibiotics
Optimal and judicious selection of
AM requires
clinical judgmentadequate knowledge of pharmacological
and microbiological factors
knowledge of the most likely infectingmicroorganisms and their susceptibility
to AMA.
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ANTIBIOTIC COMBINATIONANTIBIOTIC COMBINATION
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Clinical Indications of ABClinical Indications of AB
CombinationCombination
Empirical therapy ofsevere infections in
which the cause is unknown
Treatment ofpolymicrobial infections To have synergistic effect in specific
infection (endocarditis, Ps. aeruginosa, H.
influenza infection). To prevent the emergence of resistant
microorganism (tuberculosis, H. pylori)
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Disadvantages of ABDisadvantages of AB
CombinationCombination
Increase risk of toxicity
Selection of multiple drug resistant
microorganisms. Eradication of normal host flora with
subsequent superinfection.
Increase cost to patients Possibility of antagonistic effect
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The use ofThe use ofmore medication than ismore medication than is
clinically indicated or warranted.clinically indicated or warranted. 5 or more drugs5 or more drugs
or even moreor even more
PolypharmacyPolypharmacy
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The use of multiple drugs is often essentialThe use of multiple drugs is often essential(or event unavoidable)(or event unavoidable) to improve therapeutic effectivenessto improve therapeutic effectiveness
to reduce the dose of each drugto reduce the dose of each drug to delay the emergence of resistantto delay the emergence of resistant
microorganisms or malignant cellsmicroorganisms or malignant cells
in cardiovascular diseasesin cardiovascular diseases
However, the use of multiple drugs increasesHowever, the use of multiple drugs increasesthe risk of ADR and drug-drug interactionthe risk of ADR and drug-drug interaction
PolypharmacyPolypharmacy
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1
10
100
0 2 4 6 8 10 12 14 16 18 20
number of drugs take
percentofpa
tientswithADR
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Polypharmacy in thePolypharmacy in the
ElderlyElderly
How Bad Can It Be?How Bad Can It Be?
Elderly = 12% of population butElderly = 12% of population but
32% of prescriptions32% of prescriptions
Average use for personsAverage use for persons 65652 to 6 prescription drugs +2 to 6 prescription drugs +
1 to 3.4 over-the-counter medicine1 to 3.4 over-the-counter medicine
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Polypharmacy in thePolypharmacy in the
ElderlyElderly
Polypharmacy leads to:Polypharmacy leads to:
More adverse drug reactionsMore adverse drug reactions
Decreased adherence to drug regimensDecreased adherence to drug regimens
Increase risk of interactionIncrease risk of interaction
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Drug-Drug Interactions
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The incidence of significant clinical drug-druginteractions: 3 to 5% in patients taking a few drugs
20% in patients receiving 10 to 20 drugs
Drug-drug interactions: Pharmeceutical
Pharmacokinetics Absorption
Distribution Metabolism
Elimination
Pharmacodynamic
Drug-Drug Interactions
Ph ki tiPh ki ti
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PharmacokineticPharmacokinetic
interactioninteraction
AbsorptionAbsorption Antacids, sucralfate with most other drugsAntacids, sucralfate with most other drugs
Give sufficient interval between antacid and othersGive sufficient interval between antacid and others
H2 antagonists and PPI alter gastric pH and mayH2 antagonists and PPI alter gastric pH and mayhave influence on other drugs absorptionhave influence on other drugs absorption
Anticholinergics slower gastric motility and increaseAnticholinergics slower gastric motility and increaseabsorption of other drugsabsorption of other drugs
DistributionDistribution Displacement of drug from protein bindingDisplacement of drug from protein binding
PharmacokineticPharmacokinetic
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PharmacokineticPharmacokinetic
interactioninteraction
Metabolism
Mostly: oxidation by cytochrome P450 (CYP)
There are + 50 isoenzymes of CYP
Major CYPs for drug metabolism :
- CYP3A4/5 - metabolised > 50% drugs for human
- CYP2D6 -
- CYP2C9, CYP2C19
- CYP1A2 - previously known as cytochrome P448
- CYP2E1
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MetabolismMetabolism
Phenobarbital, rifampicin, phenytoin:Phenobarbital, rifampicin, phenytoin: inducesinduces cyt P-cyt P-
450450
increases metabolism of other drugsincreases metabolism of other drugs
warfarin, quinidine, corticosteroids, estrogen contraceptives,warfarin, quinidine, corticosteroids, estrogen contraceptives,
theophylline, mexiletine, and some b-blockers.theophylline, mexiletine, and some b-blockers.
Erithromycin, cimetidin:Erithromycin, cimetidin: inhibitsinhibits cyt P-450cyt P-450
inhibits metabolism of other drugsinhibits metabolism of other drugs
Alcohol, phenobarbital:Alcohol, phenobarbital: autoinductionautoinduction of CYPof CYP
drug tolerancedrug tolerance
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CYP3A4 : substrates
lidocaine erythromycin lovastatin
quinidine clarithromycin simvastatin
amiodarone cortisol atorvastatin
diltiazem dexamethasone ritonavir
verapamil estradiol indinavir felodipine tamoxifen
carbamazepine cyclosporin
alprazolam terfenadinemidazolam astemizole
triazolam cisapride
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CYP3A4 : inhibitors & inducers
Inhibitors Inducers
ketoconazole ritonavir phenobarbital
itraconazole indinavir phenytoin
erythromycin grapefruit carbamazepine
clarithromycin rifampicin
nefazodone dexamethasone
fluvoxamine St. Johns wort
fluoxetine
diltiazem
verapamil
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Some IrrationalSome Irrational
PrescribingsPrescribings Antibiotic in viral infectionAntibiotic in viral infection
Antibiotic used relied on laboratoryAntibiotic used relied on laboratory
results (exp. Widal)results (exp. Widal)
Albumin to treat edema afterAlbumin to treat edema afteroverhydrationoverhydration
IVIG for tIVIG for thhrombocytopenia of denguerombocytopenia of dengue
feverfever Too much vitaminsToo much vitamins
Unnecessary immunostimulantsUnnecessary immunostimulants
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Pearls of RDU
First consider the Benefit-Risk ratio (the Benefit
should always outweigh the Risk)
Used the most established drugs
Used the drugs that you know best
Use the lowest effective doses.
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Frequent reviews of therapeutic results
Discontinuation of those drugs that did not achieve
the endpoint desired or are no longer required.
Chose the most convenient (safe) way ofadministration
Always be updated in drug information
Pearls of RDU