Fmk6. Rational Drug Use

8/6/2019 Fmk6. Rational Drug Use

1/38

PENGGUNAAN OBATPENGGUNAAN OBATSECARA RASIONALSECARA RASIONAL

(Rational Drug Use)(Rational Drug Use)

NafrialdiNafrialdi

Departemen Farmakologi FKUIDepartemen Farmakologi FKUI


2/38

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.


3/38

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


4/38

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


5/38

THERE IS NO CLEAR CUT BETWEENTHERE IS NO CLEAR CUT BETWEEN

RATIONAL AND IRRATIONALRATIONAL AND IRRATIONAL

IR

RA

TION

AL

RATI

ONAL


6/38

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


7/38

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


8/38

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


9/38

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


10/38

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/


11/38

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 ?


12/38

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


13/38

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


14/38

5. Start Treatment5. Start Treatment

Verify the appropriateness of drugs

Indication, doses, duration

Efficacy

Safety

Suitability

Affordability ( cost)


15/38

Is therapeutic goals obtained ?

Under treatment ?

Over treatment ? When to stop treament ?

6. Monitor the Outcome/ Evaluation6. Monitor the Outcome/ Evaluation


16/38

Some Important IssuesSome Important Issues

Antibiotic misuseAntibiotic misuse

Antibiotic combinationAntibiotic combination

PolypharmacyPolypharmacy

Drug-drug InteractionDrug-drug Interaction

16


17/38

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..


18/38

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


19/38

The first consideration inThe first consideration in

selecting antimicrobial isselecting antimicrobial is

whether it is even indicated.whether it is even indicated.


20/38

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.


21/38

ANTIBIOTIC COMBINATIONANTIBIOTIC COMBINATION


22/38

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)


23/38

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


24/38

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



25/38

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



26/38

1

10

100

0 2 4 6 8 10 12 14 16 18 20

number of drugs take

percentofpa

tientswithADR


27/38

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


28/38

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


29/38

Drug-Drug Interactions


30/38

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


31/38

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



32/38


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


33/38

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


34/38

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


35/38

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


36/38

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


37/38

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.


38/38

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

Documents

Fmk6. Rational Drug Use