Bagian Farmakologi & Terapi Fakultas Kedokteran Universitas Andalas FARMAKOLOGI KLINIK Rahmatini Bagian Farmakologi & Terapi Fakultas Kedokteran Universitas Andalas

DEFINISI WHO ( 1988) Disiplin dalam bidang kedokteran berdasarkan prinsip ilmiah, menyatukan keahlian farmakologi & keahlian klinik dengan tujuan meningkatkan manfaat & keamanan obat

Terapi Efektif, Aman , Rasional TUJUAN FARMAKOLOGI KLINIK Terapi Efektif, Aman , Rasional

RATIONAL DRUG USE Benefit – Risk - Cost Ratio F.Kinetika F Dinamika F Ekonomi

PHARMACOLOGICAL ASPECTS IN CLINICAL PRACTICE Pharmacokinetic Pharmacodynamic How drugs act The dynamics of drug conc. in the body * Absorption / bioavailability * Distribution * Biotransformation * Excretion

THERAPEUTIC DRUG MONITORING (TDM)

Measuring the plasma drug conc. Provide useful information about the adequacy of the dosage regimen or the likehood toxicity

Measuring/ interpreting plasma drug conc. Therapeutic Drug Monitoring (TDM) Ph dynamic Ph kinetic Drug-interaction Measuring/ interpreting plasma drug conc. Therapeutic response Side effects Toxic effects

Time-drug conc. relationship 40 30 Drug toxicity 20 Drug conc. (mg/l) 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 2. To assess drug toxicity drug treatment To see whether there is therapeutic response 2. To assess drug toxicity 3. To assess compliance

DRUG THERAPEUTIC TOXIC DIGOXIN 0,0010-0,0022 µg/ml > 0,0025 DIPHENYLHI DANTOIN 10- 20 > 25 LIDOCAIN 1,5-5 > 9 PHENOBARBITAL 15-30 > 40 THEOPHYLINE 10-20 > 20

the toxic effects of a drug Nausea / anorexia / arrythmias 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

Pharmacokinetic parameters Cmax (peak) Drugs- plasma conc. Half life AUC 24 Cmin (trough) Time

Visualisation of half-life First order elimination of a drug (t ½ : 2 hours) The plasma conc. falls by half each half-life 20 Drug conc. (mg/l) t ½ 10 t ½ 5 t ½ 2.5 2 4 6 Hours

Clinical application of half life (t½) * Designing drug dosage regimen * Determining time to reach steady state drug level which show clinical effect * Determining time to reach the drug level which have no clinical effect anymore

RATIONAL & GOOD CLINICAL THERAPY CONSIDERATION Ph’kinetic Ph’dynamic Ph’economic RATIONAL & GOOD CLINICAL THERAPY

SESUNGGUHNYA BAGIMU, ADA MALAIKAT- MALAIKAT YANG SELALU MENGAWASI PEKERJAANMU QS 82 :10