FARMAKOLOGI KLINIK 2

dr. Gestina Aliska, Sp.FK

Bagian Farmakologi & Terapi Fakultas
Kedokteran Universitas Andalas
 WHO

Clinical Pharmacology is the scientific

discipline that involves all aspects of the
relationship between drugs and humans

The term ’clinical pharmacologist’ is commonly used

in the professional sense to refer to physicians who
are specialists in clinical pharmacology.
 Therapeutic drug monitoring
 Dose adjustment
 Clinical Use of Pharmacokinetic data
1. Pharmacology
 Pharmacodynamics.

 Pharmacokinetics.

2. Therapeutic evaluation
 Whether a drug is of value.

 How it may best be used.

 Formal therapeutic trials.

 Surveillance studies for both efficacy and safety (adverse

effects) – pharmacoepidemiology and pharmacovigilance.
3. Control
 Rational prescribing and formularies.

 Official regulation of medicines.

 Social aspects of the use and misuse of medicines.

 Pharmacoeconomics.
 Clinical Pharmacology in Pediatrics
 Clinical Pharmacology in Pregnancy
 Clinical Pharmacology in Geriatric
 etc
 Teaching

Patient Care Clinical Research

Pharmacology

Goverment
 clinical care of patients can be improved
 The RATIONAL USE of medicines  individual
patients & patient populations
 Clinical care of paediatric and geriatric patients needs
special attention
 the critical evaluation of new and old therapies 
pharmacoepidemiological
 Drug and Therapeutics Committees where they help
the rational introduction and use of new and
expensive medicines into the delivery of health care.
 Therapeutic drug monitoring

 Monitoring adverse reactions

Measuring the plasma drug conc.

Provide useful information about

the adequacy of the dosage
regimen or the likehood toxicity
Therapeutic Drug Monitoring (TDM)

Ph kinetic Ph dynamic

Drug-
interaction
• Measuring/ • Therapeutic
interpreting response
plasma drug conc. • Side effects
• Toxic effects
 Time-drug conc. relationship
40

30
Drug toxicity

20

Therapeutic level
10
m.e.c
Low therapy

1 2 3 4
Time (hour)
 Therapeutic Drug Monitoring (TDM)

1. Narrow margin of safety drugs

2. Drugs for prevention/ therapy of life threatening

diseases or life saving drugs

3. Difficulty in ditinguishing between the effects

of a disease and the toxic effects of a drug
4. Potent drugs  drug amount is very small
5. Drugs that show variability of drug conc.
in plasma
Factors that modify drug plasma
concentration for a given dose

• Drug formulation
• Drug interaction
• Environmental factors
• Genetic variation
• Renal and hepatic function
Reasons for monitoring
drug treatment

1. To see whether there is

therapeutic response

2. To assess drug toxicity

3. To assess compliance
Examples of difficulty in ditinguishing between
the effects of a disease and
the toxic effects of a drug

1. Digoxin toxicity Congest.Heart Failure

Nausea / anorexia / arrythmias

2. Gentamycin toxicity Gram (–) septicaemia

Renal damage
 Renal failure  Stage of failure
◦ penyesuaian dosis pada gangguan fungsi ginjal tidak
diperlukan jika
 (a) fraksi obat yang diekskresi utuh oleh ginjal (fR) < 0.33
dan metabolitnya tidak aktif, berapapun LFGnya, dan juga
 (b) pada gangguan fungsi ginjal ringan atau LFG > 0.67
nilai normal, berapapun fRnya.
◦ penyesuaian dosis diperlukan pada semua derajat
gangguan fungsi ginjal
 untuk obat dengan margin of safety yang sempit dan
eliminasi terutama melalui ginjal, misalnya
aminoglikosida, vankomisin, dan digoksin.
 Hepar impairment
 Rumus Cockcroft & Gault
 Penyesuaian dosis pada gagal ginjal terutama
dilakukan untuk DM (dosis pemeliharaan)
dengan menggunakan persamaan Giusti-
Hayton sbb. :
ClCrU
G = 1 – fR 1 –
ClCrN
G = faktor koreksi Giusti-Hayton
ClR
fR = fraksi eliminasi obat oleh ginjal
ClT
ClCrU = klirens kreatinin pada uremia
ClCrN = klirens kreatinin normal
 Penurunan DM dengan interval T yang tetap
DMU = DMN x G
◦ DMU = DM pada uremia
◦ DMN = DM yang normal

 Perpanjangan interval dosis dengan DM yang

tetap
IU = IN x 1/G
◦ IU = interval dosis pada uremia
◦ IN = interval dosis yang normal
 Seorang pasien laki-laki berusia 60 tahun
datang dengan keluhan demam sejak 3 hari
yang lalu. Keluhan disertai batuk berdahak.
Dari pemeriksaan fisik dan penunjang, dokter
mendiagnosis dengan sepsis ec.
Bronkopneumonia.
 Rencana terapi :
◦ Levofloxacin : 1x 750 mg
◦ Gentamisin : 7 mg/kgBB/hari  BB : 60 kg
 Setelah 1 hari terapi didapatkan hasil
pemeriksaan fungsi ginjal :
 Kreatinin serum: 0,8 mg/dL
Pharmacokinetic parameters

Cmax (peak)

Half life
AUC 24

Cmin
(trough)
Time
 Visualisation of half-life
First order elimination of a drug (t ½ : 2 hours)
20 The plasma conc. falls by half each half-life

10
t½

5 t½
2.5 t½

2 4 6
Hours
Clinical application of half life (t½)

1. Designing drug 2. Determining time to

dosage regimen reach steady state drug
level which show clinical
effect

3. Determining time to reach the drug level

which have no clinical effect anymore