FARMAKODINAMI

Dr. dr. nurdiana, Mkes Lab. Farmakologi FKUB

DOSIS (R/)
DOSIS YG DIMINUM

Faktor-2 FK A D M E KONSENTRASI OBAT DI TEMPAT KERJA Faktor-2 FD

reseptor homeostatik

Fisiologik Patologik Genetik Umur Interaksi

EFEK / RESPON Px
terapeutik toksik

Food-Drug Interaction

For example, a drug that causes chronic nausea or mouth pain may result in poor intake and weight loss

PRINSIP KERJA OBAT

Obat tidak menimbulkan fungsi baru, tetapi mempengaruhi/memodulasi fungsi yang sudah ada
Tidak ada obat yang mempunyai efek tunggal

(efek terapeutik dan efek samping) Efek obat ditentukan oleh interaksinya dengan proses biologi di tubuh mengubah kecepatan kegiatan faal tubuh

EFEK OBAT (farmakologi):

Efek terapi efek obat yang dikehendaki untuk tujuan terapi, timbul pada dosis terapi Efek samping efek obat yang tidak dikehendaki, timbul pada dosis terapi, sering merugikan, dapat berupa efek farmakologi yang lain atau reaksi hipersensitif (alergi) Efek toksik efek obat yang tidak dikehendaki, timbul pada dosis toksik/ supramaksimal

Tolerans : terjadi pada tingkat f.kinetik & f.dinamik Resistens Takhifilaksis Idiosinkrasi

Sinergisme : Efek kombinasi dari 2 (/lebih) macam obat yang saling menunjang Addisi : Bentuk sinergisme obat dimana efeknya merupakan efek penambahan obat tersebut (mis. 1+1=2) Potensiasi : Bentuk sinergisme obat dimana efeknya lebih besar dari efek penambahan masing-masing obat (mis. 1+1>2) Antagonis : Efek 2 macam obat yang berlawanan

LOCUS OF ACTION RECEPTORS

TISSUE RESERVOIRS

Bound

Free

Free

Bound

ABSORPTION

Free Drug Bound Drug

SYSTEMIC CIRCULATION

EXCRETION

BIOTRANSFORMATION

EFEK OBAT

INTERAKSI OBAT DENGAN RESEPTOR PADA SEL SUATU ORGANISME

PERUBAHAN BIOKIMIAWI DAN FISIOLOGI

RESPON (KHAS UTK MASING-MASING OBAT)

Farmakodinami mempelajari : Efek obat (biokimiawi & fisiologis) pada sistim biologik serta mekanisme kerjanya
Efek obat : Sebag besar ok interaksi obat dg reseptor, sebagian lagi tdk melalui resept Reseptor obat : Makromolekul (protein) pada sistim biologik yang dapat merubah fungsi sistim tsb ok interaksinya dg obat

Definisi

Efficacy
Derajat kemampuan obat menghasilkan respon yang diinginkan

Potency

Jumlah obat yang dibutuhkan untuk menghasilkan respon terhadap obat Digunakan untuk membandingkan komponen kandungan di dalam golongan obat

Definisi

Effective Concentration 50% (ED50)

Concentration of the drug which induces a specified clinical effect in 50% of subjects Concentration of the drug which induces death in 50% of subjects

Lethal Dose 50% (LD50)

Definisi

Therapeutic Index

Measure of the safety of a drug Calculation: LD50/ED50 Margin between the therapeutic and lethal doses of a drug

Margin of Safety

Dose-Response Relationship

Drug induced responses are not an all or none phenomenon Increase in dose may:

Increase therapeutic response Increase risk of toxicity

RESEPTOR UNTUK

LIGAND ENDOGEN OBAT hormon nerotransmiter

AGONIS : SUBSTANSI YANG EFEKNYA MENYERUPAI SENYAWA ENDOGEN/LIGAND ANTAGONIS : MENGHAMBAT EFEK SUATU AGONIS DI TEMPAT IKATAN AGONIS

Kompetitif
Non kompetitif

Agonis

obat yang mampu berikatan dg reseptor dan menimbulkan efek (afinitas +, aktivitas intrinsik +)
obat yang mampu berikatan dg reseptor tetapi tidak dapat menimbulkan efek (afinitas +, aktivitas intrinsik - ) ikatan dg reseptor dpt digeser oleh agonis (Emax sama, ED50 beda) ikatan dg reseptor kuat, Emax lebih rendah

Antagonis

Antagonis kompetitif

Antagonis ireversibel

FUNCTIONAL ANTAGONISTS
1.

Physiologic Antagonists
Chemical Antagonist

2.

Agonists and Antagonists

Physiologic ANTAGONIST

A drug that binds to a non-related receptor, producing an effect opposite to that produced by the drug of interest. Its intrinsic activity is = 1, but on another receptor.

Glucocorticoid Hormones Insulin

Blood Sugar Blood Sugar

Agonists and Antagonists

Chemical ANTAGONIST

A chelator (sequester) of similar agent that interacts directly with the drug being antagonized to remove it or prevent it from binding its receptor. A chemical antagonist does not depend on interaction with the agonists receptor (although such interaction may occur).

Heparin, an anticoagulant, acidic

If there is too much bleeding and haemorrhaging

Protamine sulfate is a base. It forms a stable inactive complex with heparin and inactivates it.

Polar

Nonpolar

Polar

RESEPTOR
*RESEPTOR TRANSMEMBRAN - IKT. ENZIM - KANAL ION - IKT. G-PROTEIN *RESEPTOR DI SITOSOL

KOMUNIKASI SEL INTRA SEL ANTAR SEL

TRANSDUKSI SINYAL
MOLEKUL LIGAND RESEPTOR ( TARGET SEL) EFEKTOR EFEK BIOLOGI 2nd messenger
(cAMP, IP3, DAG)

1ST messenger

Komunikasi sel

Classification Receptor
Transduction Mechanisms
1. 2.

3.

4.

Ion channel linked receptors e.g. Ach nicotinic (Na+) and GABA (Cl-) G protein & second messenger generation, adenylate cyclase stimulation or inhibition - cAMP, guanylate cyclase - cGMP, phospholipase C IP3,DAG Some receptors are themselves protein kinases Intracellular receptors (e.g. corticosteroids, thyroid hormone)

Transmembrane Signaling Mechanisms

= drug

Out In

G X Y

gene

Change in the Receptor activation cons.of second messenger of a G protein

Inactivation mechanism

G prot regulation of an enzyme or ion channel

The Major Effectors and Intracellular Second Messengers in GPCR Systems

2nd messenger

Effector

adenylyl cyclase
phospholipase C

cyclic AMP (cAMP)

calcium, DAG, and
phosphoinositide (IP3)

Obat dan Efek

D +R
agonis adr beta
Gs

DR

Efek

GDP GTP GDP

GTP

Adenilat siklase

ATP

Enzim

ATP

cAMP

2C ADPEnzim-PO4 2R

R2C2 Protein kinase

EFEK

Mechanism of beta-1 receptor activation in cardiac muscle

Effect of beta-2 receptor activation on smooth muscle

Effect of alpha-1 /muskarinik3(M3) receptor activation of smooth muscle contraction

Intracellular Mechanism: Steroid

Nucleus
XXXXXXXXXXXXX

Effects Protein RNA mRNA

drug

Plasma

Speed of responses

Agonist vs antagonist
K+1
Ag

K-1

Ag

Response

K+1 Ant

R K-1

Ant

Agonist & Antagonist

Agonist & Antagonist

PENGATURAN FUNGSI RESEPTOR

BILA SUATU SEL DIRANGSANG TERUS MENERUS OLEH AGONISNYA DESENSITISASI

BILA RANGSANGAN PADA RESEPTOR BERKURANG SECARA KRONIK, MISAL PEMBERIAN BLOCKER JANGKA PANJANG SUPERSENSITIVITAS (HIPERAKTIVITAS) TERHADAP AGONIS

Faktor faktor yg mempengaruhi Farmakokinetik & Farmakodinamik

Umur : bayi, lansia
Interaksi : makanan, obat Farmaseutik Farmakokinetik Farmakodinamik

Individual patient variations in drug responses

Body weight and composition Age of client(young and old) Diet and Nutrition Ethnic origin Genetics

Pathophysiology(eg. Kidney disease, liver disease etc.) Immunity Psychology Environment

OBAT YANG BEKERJA MELALUI RESEPTOR :

Contoh : OBAT YANG BEKERJA PADA SISTEM SARAF OTONOM
AGONIS NOREPINEFRIN RESEPTOR ADRENERGIK 1 ADRENALIN/EPINEFRIN RESEPTOR ADRENERGIK DAN SALBUTAMOL RESEPTOR ADRENERGIK 2 ASETILKOLIN RESEPTOR NIKOTINIK DAN MUSKARINIK

ANTAGONIS/BLOCKER PRAZOSIN ANTAGONIS RESEPTOR ADRENERGIK 1 PROPRANOLOL ANTAGONIS RESEPTOR ADRENERGIK 1 ATROPIN ANTAGONIS RESEPTOR MUSKARINIK

OBAT YANG BEKERJA TIDAK MELALUI RESEPTOR :

PERUBAHAN ASAM BASAANTASIDA Mg(OH)2, Al (OH)3 PERUBAHAN SIFAT OSMOTIK DIURETIK OSMOTIKUREA, MANITOL

GLISEROLMENGURANGI OEDEM SEREBRAL

GANGGUAN FUNGSI MEMBRANANESTESI UMUMETER

HUBUNGAN DOSIS-RESPON Graded dose-responses

One tissue/organ can yield the full response range
Full agonist
Response Agonist concentration [A]

Emax & ED50

Emax
Response

Emax

ED50

ED100

Log concentration [A]

Therapeutic and Toxic Effects are Dose-Related: Phenobarbital

Sleep

Death

ED50

LD50

Dose of Phenobarbital

Autonomic Pharmacology

Central Nervous System (CNS) Peripheral Nervous System

Somatic Nervous System Autonomic Nervous System (ANS)

Sympathetic Branch Parasympathetic Branch

Autonomic Nervous System Characteristics Feed or Breed Fight or Flight

ANS Anatomy & Physiology

The nerves of the ANS exit the CNS and subsequently enter specialized structures called autonomic ganglia

Preganglionic fibers

Pass between the central nervous system and the ganglia Pass between the ganglia and the effector organ

Postganglionic fibers

Sympathetic versus Parasympathetic

Sympathetic ganglia

Located close to the spinal cord or midway between the spinal cord and the effector organ

Parasympathetic ganglia

Located close to or within the walls of the target organs

Cholinergic and Adrenergic Fibers

Cholinergic

Fibers that release acetylcholine All preganglionic and postganglionic of the parasympathetic division

Adrenergic

Fibers that release norepinephrine Most postganglionic fibers of the sympathetic division are adrenergic, but some are cholinergic

Neurochemical Transmission

No actual physical connection exists between two nerve cells or between a nerve cell and the organ it innervates

Synapse

Space between nerve cells Specialized synapse between two nerve cells or a nerve cell and an organ Chemical messenger that conducts a nervous impulse across a synapse

Neruroeffector junction

Neurotransmitter

PREGANGLION

POST GANGLION
PARASIMPATIS Otot jantung ACH NIC ACH MUS Otot polos < < Glandula

MEDULLA
ACH NIC

<
ACH MUS

SIMPATIS Kel. Keringat

<
ACH NIC

<
NE alpha beta

<
SPINALCORD
ACH NIC

SIMPATIS Otot jantung Ot.polos p darah

<
ACH NIC

D1 D

<

<

EPINEPRINE

SIMPATIS Pemb. Darah Ginjal

ADRENAL MEDULLA ACH NIC

SOMATIC Otot rangka

<

VOLUNTARY MOTOR NERVE

Neurotransmission

Neurotransmitters

Acetylcholine

Preganglionic nerves of sympathetic nervous system Preganglionic and postganglionic nerves of the parasympathetic nervous system Postganglionic nerves of the sympathetic nervous system

Norepinephrine

Acetylcholine

For cholinergic synapses acetylcholine molecules combine with cholinergic receptor molecules

Nicotinic Receptors

Produces an excitatory response Produce an excitatory or inhibition, depending on where the target receptors are found

Muscarinic Receptors

Norepinephrine

For adrenergic synapses norepinephrine molecules combine with adrenergic receptor molecules

Alpha Receptors

Blood vessels Heart Lungs

Beta Receptors

farmako@fk.unibraw.ac.id nurdianafarmako@yahoo.com