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General Pharmacology
Ari YSekolah Tinggi Farmasi Bandung
2 13Ari Y - STF Bandung'13
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Pharmacology
Pharmakocinetics/Drug Metabolism
BiochemicalPharmacology
MolecularPharmacology
Chemotherapy
Systems PharmacologyNeuropharmacologyCardiovascular pharmacologyGastrointestinal pharmacologyImmuno pharmacologyRespiratory pharmacology
Pharmacogenetic
GENETICS
Pharmacogenomic
GENOMIC PharmacoepidemiologyCLINICAL EPIDEMOLOGY
Pharmacoeconomics
HEALTH ECONOMICS
PSYCHOLOGY
Psycho
pharmacology
CLINICAL MEDICINE/
THERAPEUTICS
Clinicalpharmacology
VETERINARY
Veterinary
pharmacology
PHARMACYPharmaceutical
sciences
BIOTECHNOLOGY
Biopharmaceutics
PATOLOGY
Toxicology
CHEMISTRY
ChemistryMedical
pharmacology
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Know thedisease
Know the drug
Know thepatient
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Know the drug
Mechanism of Action
Dose-response relationship(how to adjust doses)
Sources of variability
pharmacokineticpharmacodynamic
Expected effects
beneficialadverse
Mechanism of Action
Dose-responserelationship (how to adjustdoses)
Sources of variabilitypharmacokineticpharmacodynamic
Expected effectsbeneficialadverse
Drug interactionAri Y - STF Bandung'13
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GENERALPHARMACOLOGY
PharmacokineticsPharmacodynamics
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Pharmacology
Pharmacokinetics
Pengaruh tubuh thd
obat
Pharmacodynamics
Pengaruh obat thd
tubuhDrug Drug
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Pharmacokinetics
QualitativeAbsorption
DistributionMetabolism
Elimination
QuantitativePharmacokinetics parameter(T , Vd, Cl, AUC)
PK PD ModelTherapeutic Drug Monitoring
Drug Drug Interactions
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Pharmacodynamics
Type of Pharmacology effectsReceptor ConceptsDrug Mechanisms
Dose response relationships
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General Pharmacology
PharmacokineticsPharmadynamics
The Right drug
The Right patient
The Right dose The Right time
The Right ResponseAri Y - STF Bandung'13
Ad i i d
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Phases of Drug Activity
Disintegration - Dissolution
Absorption
Distribution
Metabolism
Elimination
Drug Recept. interaction
Pharmacology Effect
Therapy Effect
Side Effect
Toxic Effect
Pharmaceutics Phase
Pharmacokinetics Phase
Pharmacodynamics Phase
Pharmacotherapy Phase
- Sources ofindividualvariation
- Drug interactions
Genetics,
Physiology,Pathophysiology
-Medication errors- Patient compliance
Administereddose
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Basic Process of
Pharmacokinetics
Absorption Distribution
blood
Tissues
Site of
Action
Metabolism
Excretion
GITliver
kidney
AnotherRoute
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Absorption Process
Biotransport Mechanism pH Partition Theory
Route of Administration First Pass Effects (FPE)
Bioavaibility
Other factors
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Biotransport
External Barrier (Outer systemic)Blood Tissue Barrier (Blood / plasmatissue / organ)- General
- Specific :Blood Brain BarrierBlood CFS BarrierBlood Placenta Barrier
Blood Ocular BarrierBlood Testis Barrier
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Drug Biotransport
Vascular System
DRUG
Molecule weight & chiralitylipophilicityIonic status
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Schematic diagram of membrane
Lattice ofprotein
Lattice ofprotein
Inner lipoidalmatrix
Aqueous pores
Hydrophilic tail
Hydrophobic head
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Biotransport
ATP
ADP-Pi
passivediffusion
carrier-mediatedtransport
endocytosis
Active Facilitated
Aqueouschannels
TransporterAri Y - STF Bandung'13
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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)
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Membutuhkan carrier
Transport menjadi jenuh (saturated) pada
konsentrasi tinggi Proses selektif
Dua obat yang ditranspor oleh mekanisme ygsama akan menghambat satu sama lain
Melawan concentration gradient ( activetransport)
Tdk melawan cocentration gradient (facilitated
transport)
Memerlukan energy
Mekanisme transport dapat dihambat olehobat obat yang mempengaruhi cellularmetabolism
Properties of facilitated diffusion & active transport
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A ti T t
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Anti TransportersP-Glycoprotein (Pgp)
ATP-dependent drug efflux pump
Broad substrate specificity fordrugs: Digoxin, quinadine, and others
Coded by MDR-1 gene:
Induced by rifampin
Inhibited by verapamil,quinidine, macrolides,antifungals, etc
Expressed on some cells likeCYP3A:
Intestine: influence ofabsorption
Liver: biotransformation
Kidney: drug excretion
Brain: distributionAri Y - STF Bandung'13
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pH Partition Theory
Weak Acid : HA H++ A-Henderson-Hasselbach Equation :
pH = pK
+ Log10[A-]/[HA]
Weak Base :BH+ B + H+
Henderson-Hasselbach Equation :pH = pK+ Log10[B]/[BH
+]
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Ion Trapping /Ph-Partition - Theory Obat obat merupakan asam lemah atau basa lemah
aspirin, barbiturates (acid) : propranolol, opioids (base)
Asam lemah : HA==H++ A-Persamaan Henderson-Hasselbach :
pH = pK+ Log10[A-]/[HA]
Basa lemah :BH+==B + H+
Persamaan Henderson-Hasselbach :
pH = pK
+ Log10[B]/[BH+]pKa dari suatu obat : pH obat dlm bentuk 50% ionised dan50% unionised
aspirin (pKa=3.5 ):pada pH =3.5 50% U/I
propranolol (pKa= 9.4) : pada pH = 9.450% U/I
Makin asam pH makin banyak obat asam dlm bentukunionized, dsb untuk obat basa
Unionized fraction : lipid soluble dan mudah menembus cellmembranes. Ionized fraction : lipid insoluble dan sulitmenembus membran
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Weak Acid Weak Base
H+
HA A-
HA
H+
A-
B BH+
H+
H+
B BH+
ionized = polar = water soluble
non-ionized = nonpolar = more lipid-solubleAri Y - STF Bandung'13
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Route of Administration
Oral
Sublingual
Rectal
ENTERAL
Intravenous (IV)
Intra-arterial (IA)Subcutaneous (SC)
Intradermal (ID)
Intramuscular (IM)
Intraperitoneal (IP)Lungs (Inhalation)
Skin (Topical)
PARENTERAL
Nose (Intranasal)
Eye (Opthalmic) Ear (Otic)
Vagina
Urethra
Urinary BladderIntrathecal
Epidural
Directly Into
Target TissueAri Y - STF Bandung'13
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Route of Administration (general)
Parenteral(IV)
Inhaled
Oral
Transdermal
Rectal
Topical
Parenteral
(SC, IM)
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First-Pass Effect (FPE)
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First-pass EffectPada beberapa obat menyebabkan tidak
efektif bila digunakan peroralDosis obat p.o lebih besar dari dosis i.v
Bila obat dimetabolisme menjadi bentuk
aktif,menyebabkan kumulatif dari metabolitDipilihkan rute pemberian lainnya (misalnya,IV atau intramuscular injection)
Diberikan dosis oral permulaan yang tinggi (loading) dengan tujuan menjenuhkan liverenzymes
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DrugConcent. On
plasma
(mcg/ml)
Time (hours)
Dose
Oral Dose
IV Dose
Bioavailability = (AUC oral/AUC iv) x 100
AUC: Area Under Curve
Bioavailability
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Pl L l Ti Pl t
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Plasma Level vs Time Plots
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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 pengabsorpsianKerusakan obat pada/dekat tempatpengabsorpsianIkatan obat dengan protein
Ari Y STF Bandung'13