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VETERINARY Veterinary pharmacology CLINICAL MEDICINE/ THERAPEUTICS Clinical pharmacology PSYCHOLOGY Psycho pharmacology PHARMACY Pharmaceutical sciences BIOTECHNOLOGY Biopharmaceutics Pharmakocinetics/ Drug Metabolism Biochemical Pharmacology
Pharmacology
Chemotherapy
PATOLOGY Toxicology
Systems Pharmacology
Neuropharmacology Cardiovascular pharmacology Gastrointestinal pharmacology Immuno pharmacology Respiratory pharmacology
CHEMISTRY Chemistry
Pharmacogenetic GENETICS
Pharmacogenomic GENOMIC
CLINICAL EPIDEMOLOGY
Mechanism of Action Dose-response relationship relationship (how to (how adjust to adjust doses) doses) Sources of variability Sources pharmacokinetic of variability pharmacodynamic pharmacokinetic Know the drug pharmacodynamic Expected effects Expected beneficial effects adverse beneficial adverse Drug interaction
Ari Y - STF Bandung'13
GENERAL PHARMACOLOGY
Pharmacokinetics Pharmacodynamics
Ari Y - STF Bandung'13
Pharmacology
Pharmacokinetics Pengaruh tubuh thd obat
Drug
Pharmacokinetics
Qualitative Absorption Distribution Metabolism Elimination Quantitative Pharmacokinetics parameter (T , Vd, Cl, AUC)
PK PD Model
Pharmacodynamics
Type of Pharmacology effects Receptor Concepts Drug Mechanisms Dose response relationships
Administered dose
Pharmacokinetics Phase
Distribution Metabolism
- Sources of
Elimination
Pharmacotherapy Phase
Pharmacology Effect
Physiology, Pathophysiology
Toxic Effect
pH = 1 - 3
dissolution disintegration absorption
Pharmacological effect
hepatic metabolism
pH = 5 - 7
intestinal transit rate
dissolution
intestinal metabolism
disintegration
absorption
faeces
clearance
GIT
Metabolism
blood
Another Route
kidney Excretion
Tissues
Absorption Process
Biotransport Mechanism pH Partition Theory Route of Administration First Pass Effects (FPE) Bioavaibility Other factors
Ari Y - STF Bandung'13
Biotransport
External Barrier (Outer systemic) Blood Tissue Barrier (Blood / plasma tissue / organ) - General - Specific : Blood Brain Barrier Blood CFS Barrier Blood Placenta Barrier Blood Ocular Barrier Blood Testis Barrier
Ari Y - STF Bandung'13
Drug Biotransport
Molecule weight & chirality lipophilicity Ionic status
Vascular System
DRUG
Lattice of protein
Inner lipoidal matrix
Hydrophilic tail
Aqueous pores
Ari Y - STF Bandung'13
Biotransport
passive diffusion
carrier-mediated transport
Active
ATP ADP-Pi
Facilitated
endocytosis
Transporter
Ari Y - STF Bandung'13
Aqueous channels
Biotransport Mechanisms
Passive diffusion (Most common of drugs) Concentration gradient Only for unionized form (lipid soluble) Didnt need energy Facilitated transport (e.g. Vit. B12, Cephalosporins)
- Blood brain barrier, renal tubule Active transport (e.g., 5-fluorouracil) - Neuron,choroid plexus, renal tubule, hepatocytes Pinocytosis (up take thyroglobuline oleh thyroid follicular cell) Aqueous channels (ion- ion)
Ari Y - STF Bandung'13
Properties of facilitated diffusion & active transport Membutuhkan carrier Transport menjadi jenuh (saturated) pada konsentrasi tinggi Proses selektif Dua obat yang ditranspor oleh mekanisme yg sama akan menghambat satu sama lain Melawan concentration gradient ( active transport) Tdk melawan cocentration gradient ( facilitated transport) Memerlukan energy Mekanisme transport dapat dihambat oleh obat obat yang mempengaruhi cellular Ari Y - STF Bandung'13 metabolism
Anti Transporters
P-Glycoprotein (Pgp)
ATP-dependent drug efflux pump Broad substrate specificity for drugs: Digoxin, quinadine, and others Coded by MDR-1 gene: Induced by rifampin Inhibited by verapamil, quinidine, macrolides, antifungals, etc Expressed on some cells like CYP3A: Intestine: influence of absorption Liver: biotransformation Kidney: drug excretion Brain: distribution
pH Partition Theory
Weak Acid : HA H+ + AHenderson-Hasselbach Equation : pH = pK + Log10[A-]/[HA]
Weak Base :BH+ B + H+ Henderson-Hasselbach Equation : pH = pK + Log10[B]/[BH+]
Ari Y - STF Bandung'13
Obat obat merupakan asam lemah atau basa lemah aspirin, barbiturates (acid) : propranolol, opioids (base)
Weak Acid
H+
Weak Base
H+ B BH+
HA
A-
AHA B BH+ H+
H+
ionized = polar = water soluble Ari Y - STF= Bandung'13 non-ionized = nonpolar more lipid-soluble
Route of Administration
ENTERAL
Oral
PARENTERAL
Intravenous (IV) Intra-arterial (IA) Subcutaneous (SC) Intradermal (ID) Intramuscular (IM) Intraperitoneal (IP) Lungs (Inhalation) Skin (Topical)
Ari Y - STF Bandung'13
Sublingual
Rectal
Nose (Intranasal) Eye (Opthalmic) Ear (Otic) Vagina Urethra Urinary Bladder Intrathecal Epidural Directly Into Target Tissue
Transdermal
Parenteral (SC, IM) Rectal
Topical
First-pass Effect
Pada beberapa obat menyebabkan tidak efektif bila digunakan peroral Dosis obat p.o lebih besar dari dosis i.v Bila obat dimetabolisme menjadi bentuk aktif,menyebabkan kumulatif dari metabolit
Dipilihkan rute pemberian lainnya (misalnya, IV atau intramuscular injection) Diberikan dosis oral permulaan yang tinggi ( loading) dengan tujuan menjenuhkan liver enzymes
Ari Y - STF Bandung'13
Bioavailability
AUC: Area Under Curve
Bioavailability = (AUC oral/AUC iv) x 100 IV Dose
Oral Dose
Dose
Time (hours)
Other Factors
Kecepatan pelepasan obat dari sediaan Ukuran dan bentuk molekul (BM dan chirality) Permeabilitas membran dari obat Kelarutan dlm lipid lipophilicity/hydrophobicity) Koefisien partisi Keadaan ionisasi Luas permukaan absorpsi Aliran darah menuju tempat pengabsorpsian Kerusakan obat pada/dekat tempat pengabsorpsian Ikatan obat dengan protein
Ari Y - STF Bandung'13