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)
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 albuminChloroquin Tissue protein
Amount of drug in the body
Conc. Of drug in blood
=
Vd
Biotransformation process
Polarizationlipid soluble -------- water soluble
Deactivationmost of active drug -------- inactive
Activationprodrug --------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 groupEnzyme 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 milkRenal excretion
Glomerular FiltrationTubular active secretionReabsorption
Excretion