General Pharmacology - Absorption

8/13/2019 General Pharmacology - Absorption

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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

Ari Y - STF Bandung'13


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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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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

Documents

General Pharmacology - Absorption