PENGGUNAAN OBAT

SECARA RASIONAL
(Rational Drug Use)

Nafrialdi
Departemen Farmakologi FKUI
 Rational Drug Use

Herophilus 300 B.C (from Alexandria):

“Medicines are nothing in themselves
but are the very hands of God if
employed with reason & prudence.”
 Definition of RDU
The rational use of drugs requires that:
 patients receive medications appropriate to
their clinical needs
 in doses that meet their own individual
requirements,
 for an adequate period of time, and
 at the lowest cost to them and their
community.

WHO conference of experts, Nairobi 1985

 Irrational Drugs Use
• The use of drugs without clear indication
• The use of wrong drugs for a specific condition
requiring drug therapy
• The use of drugs with doubtful or unproven
efficacy
• The use of drugs of uncertain safety status
• Failure to prescribe available, safe, & effective
drugs
• Incorrect administration, dosages, or duration
THERE IS NO CLEAR CUT BETWEEN
RATIONAL AND IRRATIONAL

IRRATIONAL
RATIONAL
 Types of Irrational Drug
Use
• Incorrect prescribing
• Over-prescribing (dose, duration)

• Under-prescribing
• Extravagant prescribing (unnecessary drugs)

• Multiple prescribing
 Impact of Inappropriate
Use of Drugs

Reduced Waste of Risk of Psycho-social

quality of resources unwanted impacts
therapy effects

•reduced availability •patients rely on

•morbidity •increased cost
unnecessary drugs
•mortality •adverse reactions
•bacterial resistance
 Factors Underlying Irrational
Drug Use

Prescribers Drug
DrugRegulation
Regulation
Prescribers Industry
Industry
• Diagnosis Patients
Patients
uncertainty • availability of
• promotion
• lack of education, • drug • misleading unsafe drugs
training and drug misinformation • informal
information claims
prescribers
• heavy patient load • misleading • etc.
• pressure to beliefs Drug
DrugSupply
Supply
prescribe • inability to
• generalization of • inefficient
communicate
limited beliefs management
problems
• misleading beliefs • non-availability
about efficacy of required
drugs
 RATIONAL THERAPEUTIC MANEUVER

1. Define patients diagnosis

2. Define therapeutic goals: causal,
symptomatic, paliative, supportive
3. Chose therapeutic option: non
pharmacologic, pharmacologic, surgical
4. Information/instruction
5. Start treatment
6. Monitor therapeutic outcome
 1. Define Patients Diagnosis
• Anamnesis
• Physical examinations
• Advance examinations
– Laboratory
– Radiology
– Histopathology, etc
 Diagnosis
– Be selective
– Do not rely on laboratory test olone for D/
 2. 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 ?
3. Chose Therapeutic Option
Chose appropriate drug based on the
following criteria:
• Efficacy
• Safety
• Suitability
• Affordability ( cost)
 Write a clear and readable prescription
4. Give Clear Information and Instruction

• To assure patients adherence

(compliance)
• To create a good doctor-patient
relationship
• Clear instruction on:
– Drug administration
– Timing of adm. (before/after meal)
– Possible adverse effects
– Next consultation
 5. Start Treatment

• Verify the appropriateness of drugs

– Indication, doses, duration
• Efficacy
• Safety
• Suitability
• Affordability ( cost)
6. Monitor the Outcome/ Evaluation

• Is therapeutic goals obtained ?

• Under treatment ?
• Over treatment ?
• When to stop treament ?
 Some Important Issues
• Antibiotic misuse
• Antibiotic combination
• Polypharmacy
• Drug-drug Interaction

16
 Antibiotic Misuse
• Antimicrobial agents are the most commonly
used and misused of all drugs.
• The inevitable consequence : emergence of
antibiotic-resistant pathogens.
• Overprescribing remains widespread due to
diagnostic uncertainty, patient demand, and
time pressure on clinician
• Reducing inappropriate antibiotic use is thought
to be best way to control resistance..
Some Antibiotic Misuses
• Antibiotic in viral infections (exp. DHF).
• Therapy of fever 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, antibiotic
often may be used if disease is severe or life-
threatening
• The first consideration in
selecting antimicrobial is
whether it is even indicated.
 Selection of Antibiotics

Optimal and judicious selection of

AM requires
clinical judgment
adequate knowledge of pharmacological
and microbiological factors
knowledge of the most likely infecting
microorganisms and their susceptibility
to AMA.
ANTIBIOTIC COMBINATION
 Clinical Indications of AB
Combination

• Empirical therapy of severe infections in

which the cause is unknown
• Treatment of polymicrobial infections
• To have synergistic effect in specific
infection (endocarditis, Ps. aeruginosa, H.
influenza infection).
• To prevent the emergence of resistant
microorganism (tuberculosis, H. pylori)
 Disadvantages of AB
Combination

• 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
 Polypharmacy

• The use of more medication than is

clinically indicated or warranted.
• 5 or more drugs
• or even more
 Polypharmacy
• The use of multiple drugs is often essential
(or event unavoidable)
– to improve therapeutic effectiveness
– to reduce the dose of each drug
– to delay the emergence of resistant
microorganisms or malignant cells
– in cardiovascular diseases
• However, the use of multiple drugs increases
the risk of ADR and drug-drug interaction
 100

percent of patients with ADR

10

1
0 2 4 6 8 10 12 14 16 18 20
number of drugs taken
 Polypharmacy in the
Elderly
How Bad Can It Be?
• Elderly = 12% of population but
32% of prescriptions
• Average use for persons 65
– 2 to 6 prescription drugs +
– 1 to 3.4 over-the-counter medicine
 Polypharmacy in the
Elderly
• Polypharmacy leads to:
– More adverse drug reactions

– Decreased adherence to drug regimens

– Increase risk of interaction

Drug-Drug Interactions
 Drug-Drug Interactions
• The incidence of significant clinical drug-drug
interactions:
– 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
 Pharmacokinetic
interaction
• Absorption
– Antacids, sucralfate with most other drugs
 Give sufficient interval between antacid and others
– H2 antagonists and PPI alter gastric pH and may
have influence on other drugs absorption
– Anticholinergics slower gastric motility and increase
absorption of other drugs
• Distribution
– Displacement of drug from protein binding
 Pharmacokinetic
interaction
• 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
• Metabolism
– Phenobarbital, rifampicin, phenytoin: induces cyt P-
450
• increases metabolism of other drugs
• warfarin, quinidine, corticosteroids, estrogen contraceptives,
theophylline, mexiletine, and some b-blockers.
– Erithromycin, cimetidin: inhibits cyt P-450
 inhibits metabolism of other drugs
– Alcohol, phenobarbital: autoinduction of CYP
 drug tolerance
CYP3A4 : substrates
• lidocaine • erythromycin • lovastatin
quinidine clarithromycin simvastatin
amiodarone • cortisol atorvastatin
• diltiazem dexamethasone • ritonavir
verapamil • estradiol indinavir
felodipine tamoxifen
• carbamazepine • cyclosporin
• alprazolam • terfenadine
midazolam astemizole
triazolam • cisapride
CYP3A4 : inhibitors & inducers
Inhibitors Inducers
• ketoconazole • ritonavir • phenobarbital
itraconazole indinavir phenytoin
• erythromycin • grapefruit carbamazepine
clarithromycin • rifampicin
• nefazodone • dexamethasone
fluvoxamine • St. John’s wort
fluoxetine
• diltiazem
verapamil
 Some Irrational
Prescribings
• Antibiotic in viral infection
• Antibiotic used relied on laboratory
results (exp. Widal)
• Albumin to treat edema after
overhydration
• IVIG for thrombocytopenia of dengue
fever
• Too much vitamins
• Unnecessary immunostimulants
 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.
 Pearls of RDU
• 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 of
administration
• Always be updated in drug information