dr. Zulkarnain R.

MSi
Dep. Farmakologi & Terapeutik,

Fakultas Kedokteran
Universitas Sumatera
Utara
13 Oktober 2014, KBK-FAMED, FK USU

UBUNGAN PENDERITA dan DOKTE

keluhan

OBAT

keluhan

penyakit penderita

Dokter

OBAT

gejala
gejala

OBAT

etc,
etc,etc
etc
crying

fever
cough

antimicrobial
penem
agents

cipro

anxiety

dyspnea

diarrhea
insomnia

Dangerous
Doctor ?

Sakit kepala
Sakit gigi

Novalgin

Bisulan

Ponstan

Nyeri haid

Voltaren

Rematik
Gout

Feminax
Irgapan

Celebrex

etc,
etc,etc
etc
Sakit ?
Nyeri
bisul

Pegal
Linu

Asam
mefenamat
Nyeri
dada

Nyeri
haid
Sakit
in-partu
Sakit
gigi

Apakah . ?
Keluhan sama,
Diagnosa sama,
. . . . . . . . . . diterapi dengan obat
yang sama?

Rational prescription (WHO,1995)

Patient receive
appropriate medicines
according to their
clinical needs
at an appropriate
dosage,
administration
& duration
and in a way
that encourages
the patient compliance
and
at the lowest cost
to the community

Appropriate patient
( Tepat Pasien )
Appropriate indication
( Tepat Indikasi )

Appropriate drug
( Tepat Obat )
Appropriate dosage,
administration & duration
(Tepat dosis, cara & lama pemberian)

Appropriate information
( Tepat Information )
Appropriate cost
( Tepat biaya )

Kasus

Laki-laki, 32 tahun, datang ke dokter dengan keluahan batuk,

berdahak warna hijau, mual, demam dan pegal linu.
Dari pemeriksaan tensi 130/85 mmHg, nadi 112 x/menit reguler,
rhonchi kering (+), didiagnosa BRONCHITIS, diberi resep:

Codein Tab (30)

Levofloxacin Tab (15)
Parasetamol Tab (15)
Retaphyl SR Tab (10)
Salbutamol Tab (30)
Antasida Syrup (1)
Metil Prednisolon Tab (30)
Ranitidin Tab (20)
Ventolin 2,5 ml (3)
Viferron Tab (10)
Berotec Inh. (1)

Adakah yang irrasional, aneh atau lucu?

What is a P-Drug?
- a drug that is ready for action
- a drug you are going to use regularly
and with which you become familiar.
- a drug of first choice for a common condition
Not a drug for an individual patient
The P-drug concept include:
- the name of the drug
for a
- the dosage form
specific
- the dosage schedule
conditio
- the duration of treatment
n

Selecting your P(ersonal)

drugs
Guidelines for selecting P-drugs:
*Step i : Define the diagnosis
*Step ii : Specify the therapeutic objective
*Step iii: Make an inventory of
effective
group of drugs
*Step iv: Choose an effective group
according to criteria
*Step v: Choose a P-drug

DIAGNOSIS
FALSE

CORRECT

INSECURE

CLINICAL ONLY
OR
WITH DIAGNOSTIC TOOLS

FALSE
ASSUMPTION
+
IMAGINATION

THROUGH SCIENTIFIC OR
SCIENTIFIC ARGUMENT

DOCTOR :
PRIDE
PROFIT
IGNORANCE
DEFENSIVE
* THERAPY

DRUG INDUSTRY FACILITATING

SCIENTIFIC IMAGINATION
PATIENTS PRESSURE
MORE DRUGS USED
THAN NEEDED

IRRATIONALITY
+
ADVERSE REACTIONS INCREASED

Standard operating
procedure (SOP)
Anamnesis
Pemeriksaan
Diagnosis

PEDOMAN DIAGNOSIS

tentukan problema utama penderita yang

merupakan sasaran pengobatan

Pemilihan obat
Pengobatan
Evaluasi

PEDOMAN PENGOBATAN

Step 1. Define the patient problem

Laki-laki, 32 tahun, datang ke dokter dengan
keluahan batuk, berdahak warna hijau, mual,
demam dan pegal linu.
Dari pemeriksaan tensi 130/85 mmHg, nadi 112
x/menit reguler, ronchi kering (+), didiagnosa
BRONCHITIS.
Apakah problema utama pada pasien ini?

Yang dapat mematikan ???

Keluhan yang tak mengenakkan (batuk, demam)
Takikardi
Infeksi

Penggunaan ANTIBIOTIKA yang

rasional
SOP
INFEKSI

ANTIBIOTIKA
DOSIS &
PEMBERIAN

EVALUASI

KULTUR

SENSITIVITY

TEST
EDUCATED
GUESS
THERAPY

kekebalan kuman
efek samping
harga

Manifestation of Infection
Local Inflammation
initial and sometimes
final response
What is observed?

wound margins
exudates
sensations
skin temperature

Systemic Inflammation
fatigue,
malaise,
anorexia,
myalgia,
arthralgia, and
fever

The tree of antibiotics

Antimicrobial Policies: Classification

First-choice antimicrobials (non-restricted use)
Used by all prescribers without approval by senior prescribers
Safe, effective, reasonably priced antimicrobials

Restricted use
For more serious clinical conditions under certain conditions
Less safe, more expensive, newer antimicrobials
Conditions could include the following:
Specific infections known to be sensitive to the antimicrobial
medicine after culture and sensitivity testing
Empirical treatment for suspected life-threatening infections
pending the result of culture and sensitivity
Counter-signature by a senior physician approved by DTC

Reserve antimicrobials (very restricted use)

For life-threatening infections known to be resistant to other
antimicrobials
Approval needed by the DTC or microbiologist

Step 2: Specify the therapeutic objective

Laki-laki, 32 tahun, dengan keluahan batuk, berdahak
warna hijau, mual, demam dan pegal linu, takikardi
ronchi kering (+), didiagnosa BRONCHITIS.

Problema utama infeksi

What will be your therapeutic objective?

Redakan batuk?
Turunkan suhu tubuh
Redakan takikardi?
Enyahkan kuman patogen ANTIBIOTIK.

Step 3: Verify the suitability of

your P - drug
3A Are the active substance and dosage form
suitable?
Effective; Indication (drug really needed?
Convenience (easy to handle)
Safety ; Side-effects, contraindication
(high risk groups, other diseases)
Interaction (drugs, food, alcohol)
Cost
; It is always an important criterion.
Always look at the total cost of
treatment rather than the cost per unit

Pertimbangan dalam
menentukan obat pilihan
Efficacy (khasiat)
Indikasi
Safety (keamanan) Efek samping
Tolerability,
Kontra indikasi
Suitability
Cost, Price (harga) Ketersediaan

Price, always look at the total cost of treatment rather than the cost per-u

How to select the

appropriate drug
1. WHO Manual
2. The STEPS criteria:
- Safety
- Tolerability
- Effectiveness
- Price
- Simplicity

the concept of selecting P-drug

give values to the worst drug first,
the drug we would never prescribe
give it a value according to the criteria;
should be the minimum value.

Then we start ascending on the values

for the better drugs
As pain killer:
Paracetamol (=1) < NSAID (=2) < morfin (=3)

PERTIMBANGAN PEMILIHAN
ANTIBIOTIK
Tempat infeksi
Tipe infeksi
Sumber infeksi
Keadaan klinis pasien
Faktor obat /
antibiotik
Sensitivitas kuman terhadap
antibiotik

Bacteria by Site of
Infection

the concept of selecting P-drug

would never prescribe
ascending on the values for the better drugs
BRONCHITIS with PRODUCTIVE COUGH
MIS-USE
Codein Tab (30)
Tab (15)
(15)
Levofloxacin
Levofloxacin Tab
Parasetamol Tab (15)
Bronchodila
Retaphyl SR Tab (10)
Bronchodila
tor
Salbutamol Tab (30)
tor
OFF-LABEL
Antasida
Syrup DRUG
(1)
OFF-LABEL
Metil
PrednisolonDRUG
Tab (30)
Tab (20)
OFF-LABEL
DRUG
Bronchodila Ranitidin
Ventolin 2,5 ml (3)
tor
OFF-LABEL
DRUG
Tab (10)
Bronchodila Viferron
Berotec Inh. (1)
tor

Tachycardia
Tachycardia

Tachycardia
Tachycardia

STEPS framework:

Laki-laki, 32 tahun, datang ke dokter dengan keluahan batuk, berdahak

warna hijau, mual, demam dan pegal linu. Dari pemeriksaan tensi 130/85
mmHg, nadi 112 x/menit reguler, ronchi kering (+), didiagnosa BRONCHITIS

Antibiotics

Eff
Saf
Suit
AMOXICILLIN Ondansetron
3
4
4
Ramipril
GENTAMICIN
4
1
4
Micardis (telmisartan)
METRONIDAZOLClopidogrel
1
3
4
OFLOXACIN
4
3
3
Aspilet
(lisinopril
)3
LEVOFLOXACIN Noperten
4
2
Amlodipin
TETRACYCLIN
2
3
4
Meloxicam
COTRIMOXAZOL
2
2
4
RIFAMPICIN

4 = terbaik, termurah, tersedia di pasaran

1 = terburuk, termahal, tak tersedia

Price

Total

15

11

11

13

10

13

12

11

Relationship between PK
and PD

Dosage
regimen

Concentration
vs time in
plasma
Absorption
Protein binding
Distribution
Biotransformation
Excretion

Concentration
vs time in
tissue and
other body fluids

Pharmacologic
or toxicologic
effect

Concentration
vs time in
site of
infection

Antibiotic
effect vs time

pharmacokinetics

pharmacodynamics

Craig WA. Pharmacokinetic/pharmacodynamic parameters:

Rationale for antibacterial dosing of mice and men. Clin Infect Dis.
26:112,1998

PD parameters predictive
of outcome
Parameter
correlating
with efficacy
Representative

Antimicrobial
Agents

T>MIC
Penicillins
Cephalosporins
Carbapenems
Macrolides

AUC:MIC

Cmax:MIC

Azithromycin
Fluoroquinolones
Fluoroquinolones Aminoglycosides
Ketolides
Metronidazole

Organism kill Time-dependent Concentrationdependent

Concentrationdependent

Maximize
concentration
exposure

Maximize
concentration
exposure

Therapeutic
goal

Optimise
duration of
exposure

Drusano & Craig. J Chemother ;9:3844,1997

Drusano et al. Clin Microbiol Infect 4(Suppl. 2):S2741,1998
Vesga et al. 37th ICAAC 1997

Kasus

Laki-laki, 32 tahun, datang ke dokter dengan keluahan batuk,

berdahak warna hijau, mual, demam dan pegal linu.
Dari pemeriksaan tensi 130/85 mmHg, nadi 112 x/menit reguler,
rhonchi kering (+), didiagnosa BRONCHITIS, diberi resep:

Codein Tab (30)

Levofloxacin Tab (15)
Parasetamol Tab (15)
Retaphyl SR Tab (10)
Salbutamol Tab (30)
Antasida Syrup (1)
Metil Prednisolon Tab (30)
Ranitidin Tab (20)
Ventolin 2,5 ml (3)
Viferron Tab (10)
Berotec Inh. (1)

Amoxicillin !
Dosis dan cara pemberian ?

4 x 500 mg >> 2 x 1000 mg

Kalau dari uji kepekaan
dinyatakan levofloxacin
paling sensitif, maka dosis dan
cara pemberiannya

5 x 400 mg << 2 x 1000 mg

Antibiotik yang RASIONAL?

Step 4: Write a
prescription

Step 5: Give information,

instruction and warning
1.Effects of the drug:
- why the drug is needed
- which symptoms will disappear, which will not
- when the effect is expected to start
- what will happen if the drug is not taken correctly

2.Side-effects:

- what side effect will occur

- how to recognize them
- how long, how serious
- what action to take

3.Instructions:

- how and when the drug should be taken

- how long the treatment should continue
- how long the drug should be stored
- what to do with the left-over drug

Step 5: Give information,

instruction and warning
4.Warnings:
- when the drug should not be taken
- what is the maximum dose
- full treatment course should be taken

5.Future consultation:
- when to come back (or not)
- when to come back earlier
- what information the doctor will need then

6.Everything clear?
- Ask the patient whether everything is understood
- Ask the patient to repeat the most important information
- Ask whether the patient has any more question

Step 6: Monitor (and stop?)

the treatment
Was the treatment effective?
a. Yes, and disease cured;-stop the treatment
b. Yes, but not yet completed;
- any serious side effect?
= no --- treatment continue
= yes--- reconsider dosage or drug choice
c. No, disease not cured; verify all steps
= Diagnosis correct?
= Therapeutic objective correct?
= P-drug suitable for this patient?
= Drug prescribed correctly?
= Patient instructed correctly?
= Effect monitored correctly?

Selecting your P(ersonal)

drugs
Guidelines for selecting P-drugs:
*Step i : Define the diagnosis
*Step ii : Specify the therapeutic
objective
*Step iii: Make an inventory of effective
group of drugs
*Step iv: Choose an effective group
according to criteria
*Step v: Choose a P-drug

Is P-Drug the same everywhere?

P-Drug is differ
- from country to country
- from company to company
- from area to area
EVEN:
- from doctor to doctor
WHY ???
because varying in:
= availability and cost of drugs
= different country formularies and essential
drug list

Discharge Medication Guidelines for

the Secondary Prevention of CV
Disorders:
Coronary Artery Disease:
1. Aspirin
2. Statin/HmG
(ie simvastatin, atorvastatin, pravastatin)
Target LDL < 100 mg/dl
3. Beta Blocker if MI

Discharge Medication Guidelines for

the Secondary Prevention of CV
Disorders:
Heart Failure (EF < 45%)
1. ACE Inhibitor (titrated to maximize
dosage)
2. Beta Blocker (initiated and titrated as
outpatient when patient is euvolemic)
3. Spironolactone (Class III, IV HF)
4. (Digoxin, diuretics for symptoms)

Discharge Medication Guidelines for

the Secondary Prevention of CV
Disorders:
Atrial Fibrillation
1. Warfarin
Patients older than 65 yo
Patients with structural heart disease
Titrate to INR 2.0 3.0
All medications should be prescribed at time
of discharge unless a contraindication exists
and is documented

Estimated Benefit to the

Heart Failure Patient Population
550 readmissions are prevented per
year
$ 2,480,000 are saved based on avoided
readmissions
331 lives are saved per year

Estimated Benefit to the

CAD Patient Population
430 readmissions are prevented per
year
Significant cost savings
430 lives are saved per year

You Manage
What You Measure
&
Do Not Measure
What You Will Not
Manage

Pertimbangan dalam
menentukan analgetik pilihan
Analgesic

Efficacy

Safety

Contraindication

Cost

Availability
formula

Sum
score

Paracetamol

19

Ibuprofen

15

Meloxicam

11

Celecoxib

10

Codeine

15

Morphine

10

Laki-laki, 52 tahun, MIALGIA. tensi 230/135 mmHg, nadi 112 x/menit reg
0 = the worst, expensive; .; 4 = the best, cheapest

Pertimbangan dalam
menentukan obat pilihan
Grup drug
(analgesic)

Efficacy

Safety

Contraindication

Cost

Availabilit
y formula

Sum
score

Paracetamol

12

Ibuprofen

13

Diclofenac

17

Celecoxib

Codeine

13

Morphine

13

Ucok (28) tahun, nyeri akibat patah tulang akibat KLL dibawa ke IGD.
Perlu sediaan analgetika dalam bentuk injeksi
0 = the worst, expensive; .; 4 = the best, cheapest

STEPS framework:
An example of how to select a P-drug for a pt
laki2, 32 tahun, 220/150 mmHg, nadi 120 x/mnt, nafas
pendek, wajah hitam, extremitas dingin, SP paru bawah
melemah
problema utama: diastolic hypertension

DRUG*

Eff

Saf Suit Pric Ava

e
e
il

Alfa-blocker

ACE-inhibitor

ARB

Ca Channel
3
2
1
Blocker
4
= terbaik, termurah, tersedia di pasaran

1 = terburuk, termahal, tak tersedia