Drug

Body /

Living system

Actions of a drug on the body.

( Pharmacodynamics )

Actions of the body on the drugs

( Pharmacokinetics )

Drugs

( Pharmacokinetics ) Absorption

Systemic circulation

Free drug Protein bound drug

Distribution

Site of action

(Pharmacodynamics)

Biotransformation

Excretion

Absorption

Passive difusion (lipid difusion)

Filtration (aqueous difusion)

Active Transport

Passive difusion

Filtration

Transport

active

C

Endocytosis

passive difusion
(lipid difusion)

Degree of acidityDegree of ionizedLipid solubility

50 % ionized

pKa drug 3,5 dl. pH 3,5

50 % unionized

9 % ionized

dl. pH 2,5

91 % unionized

pasive lipid diffusion absorption

Weak acid drugs

In acid medium

More ionized, less unionized

Water soluble

Difficult to absorb

More unionized, less ionized

lipid soluble

Easy to absorb

In basic medium

Percentage of ionized

For weak acid

100

% ionized= -----------------

1 + antilog (pKa-pH)

For weak base

100

% ionized= -----------------

1 + antilog (pH-pKa)

contoh

Aspirin : pKa 3,5

pH lambung 2,5

Berapa % yang ionized di lambung ?

Distribution :

Size of the organ Blood flow to organ Solubility Protein binding Warfarin Plasma albumin

Chloroquin Tissue protein

Amount of drug in the body

Conc. Of drug in blood

=

Vd

Biotransformation process

Polarization

lipid soluble -------- water soluble

Deactivation

most of active drug -------- inactive

Activation

prodrug --------active drug

Biotransformation

water soluble drug

lipid soluble drug

liver

intestine

Ekskresi

excretion

Metabolism/ biotransformation

Phase I reaction / Asyntetic Oxidation (cytochroom P450) Reduction Deamination Hydrolysis Phase II reaction ( syntetic ) conjugation Glucuronate Acetate Glutathione Glycine Sulphate Methyl group

Enzyme induction / Enzyme inducer

Barbiturate : Barbiturate

(phenobarbital) Coumarin

Pill contraception

Phenytoin :Dexamethasone

Pill contraception

Merokok : Nicotine

(Nicotine ) Pill contraception

Theophyllin

Rifampicin :Pill contraception

Carbamazepine: Warfarin

Enzyme Inhibitor / inhibisi enzim

Chloramphenicol Phenytoin

Tolbutamide

Cimetidine Chlordiazepoxide

Diazepam

Chlorazepate

Phenytoin

Theophyllin

Ketokonazole

Grapefruit juice

Ritonavir

First pass effect / First pass elimination

Systemic circulation

liver

Drugs

Drugs + metabolites

Excretion of drugs

RenalGI tractLung Sweat Tear Breast milk

Renal excretion

Glomerular FiltrationTubular active secretion

Reabsorption

Excretion