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FARMAKODINAMI
Dr. dr. nurdiana, Mkes
Lab. Farmakologi FKUB
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DOSIS (R/)
DOSIS YG DIMINUMFaktor-2 FKA D M E
KONSENTRASI OBAT
DI TEMPAT KERJA
FisiologikPatologik
GenetikUmurInteraksi
Faktor-2 FDreseptorhomeostatik
EFEK / RESPON Px
terapeutik toksik
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Food-Drug Interaction
For example, a drug that causes chronic nausea ormouth pain may result in poor intake and weightloss
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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 denganproses biologi di tubuh mengubah kecepatan
kegiatan faal tubuh
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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, seringmerugikan, dapat berupa efek farmakologi yang lain atau reaksihipersensitif (alergi)
Efek toksik efek obat yang tidak dikehendaki,timbul pada dosis toksik/ supramaksimal
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Tolerans : terjadi pada tingkat f.kinetik &
f.dinamik Resistens
Takhifilaksis
Idiosinkrasi
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Sinergisme : Efek kombinasi dari 2 (/lebih)macam obat yang saling menunjang
Addisi : Bentuk sinergisme obat dimana efeknyamerupakan efek penambahan obat
tersebut (mis. 1+1=2)
Potensiasi : Bentuk sinergisme obat dimanaefeknya lebih besar dari efek penambahan masing-masing obat
(mis. 1+1>2) Antagonis : Efek 2 macam obat yang berlawanan
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Bound Free Free Bound
LOCUS OF ACTION
“RECEPTORS”
TISSUE
RESERVOIRS
SYSTEMICCIRCULATION
Free Drug
Bound Drug
ABSORPTION EXCRETION
BIOTRANSFORMATION
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EFEK OBAT
INTERAKSI OBAT DENGAN RESEPTOR PADA
SEL SUATU ORGANISME
PERUBAHAN BIOKIMIAWI DAN FISIOLOGI
RESPON
(KHAS UTK MASING-MASING OBAT)
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Farmakodinami mempelajari :Efek obat (biokimiawi & fisiologis) padasistim biologik serta mekanisme kerjanya
Efek obat :
Sebag besar ok interaksi obat dgreseptor, sebagian lagi tdk melalui resept
Reseptor obat :
Makromolekul (protein) pada sistimbiologik yang dapat merubah fungsi sistimtsb ok interaksinya dg obat
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Definisi
Efficacy
Derajat kemampuan obat menghasilkan responyang diinginkan
Potency
Jumlah obat yang dibutuhkan untuk menghasilkan respon terhadap obat
Digunakan untuk membandingkan komponenkandungan di dalam golongan obat
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Definisi Effective Concentration 50% (ED50)
Concentration of the drug which induces aspecified clinical effect in 50% of subjects
Lethal Dose 50% (LD50) Concentration of the drug which induces
death in 50% of subjects
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Definisi
Therapeutic Index
Measure of the safety of a drug
Calculation: LD50
/ED50
Margin of Safety
Margin between the therapeutic and lethaldoses of a drug
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Dose-Response
Relationship Drug induced responses are not an “all or
none” phenomenon
Increase in dose may:
Increase therapeutic response
Increase risk of toxicity
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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
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Agonis obat yang mampu berikatan
dg reseptor dan menimbulkan efek
(afinitas +, aktivitas intrinsik +)
Antagonis obat yang mampu berikatan
dg reseptor tetapi tidak dapat
menimbulkan efek(afinitas +, aktivitas intrinsik - )
Antagonis kompetitif ikatan dg reseptor dpt
digeser oleh agonis
(Emax sama, ED50 beda)
Antagonis ireversibel ikatan dg reseptor kuat,
Emax lebih rendah
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FUNCTIONAL ANTAGONISTS
1. Physiologic Antagonists
2. Chemical Antagonist
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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 Blood Sugar
Insulin Blood Sugar
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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 frombinding its receptor.
A chemical antagonist does not depend on interaction with theagonist’s 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.
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Polar
Polar
Nonpolar
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RESEPTOR
*RESEPTOR TRANSMEMBRAN
- IKT. ENZIM
- KANAL ION
- IKT. G-PROTEIN
*RESEPTOR DI SITOSOL
KOMUNIKASI SEL
INTRA SEL ANTAR SEL
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TRANSDUKSI SINYAL
MOLEKUL LIGAND 1ST messenger
RESEPTOR
( TARGET SEL)
EFEKTOR 2nd messenger
(cAMP, IP3, DAG)
EFEK BIOLOGI
Komunikasi sel
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Classification Receptor
Transduction Mechanisms1. Ion channel linked receptors e.g. Ach nicotinic
(Na+) and GABA (Cl-)
2. G protein & second messenger generation,adenylate cyclase stimulation or inhibition - cAMP,
guanylate cyclase - cGMP, phospholipase C -IP3,DAG
3. Some receptors are themselves protein kinases4. Intracellular receptors (e.g. corticosteroids,
thyroid hormone)
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Transmembrane Signaling
Mechanisms = drug
Out
In
gene
P
G
X Y
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Receptor activation
of a G protein
G prot regulation
of an enzyme or
ion channel
Change in the
cons.of second
messenger
Inactivation
mechanism
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The Major Effectors and Intracellular
Second Messengers in GPCR Systems
Effector
adenylyl cyclase
phospholipase C
2nd messenger
cyclic AMP (cAMP)
calcium, DAG, and
phosphoinositide (IP3)
Ob t d Ef k
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Obat dan Efek
D + R DR Efek
agonis
adrbeta
GDP GTP GDP
Gs
GTP
Adenilat
siklase
ATP cAMP
Enzim
Enzim-PO4
EFEK
R2C2
Protein kinase 2C
2R
ATP
ADP
Mechanism of beta 1 receptor activation in
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Mechanism of beta-1 receptor activation in
cardiac muscle
Effect of beta 2 receptor activation
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Effect of beta-2 receptor activation
on smooth muscle
Effect of alpha-1 /muskarinik3(M3) receptor activation
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Effect of alpha-1 /muskarinik3(M3) receptor activation
of smooth muscle contraction
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Intracellular Mechanism: Steroid
Plasma
R
Nucleus
XXXXXXXXXXXXX
RNA
mRNAProtein
Effects
drug
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Speed of responses
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Agonist vs antagonist
Ag
K +1
K -1 Ag
Ant
K +1
K -1
+
+
Response
Ant
R
R
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Agonist & Antagonist
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Agonist & Antagonist
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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
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Faktor faktor yg mempengaruhiFarmakokinetik & Farmakodinamik
Umur :
bayi, lansia
Interaksi :
makanan, obat
Farmaseutik
Farmakokinetik
Farmakodinamik
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Individual patient variations indrug responses
Body weight andcomposition
Age of client(youngand old)
Diet and Nutrition
Ethnic origin
Genetics
Pathophysiology(eg.Kidney disease, liverdisease etc.)
Immunity
Psychology
Environment
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OBAT YANG BEKERJA MELALUI RESEPTOR :
Contoh : OBAT YANG BEKERJA PADA SISTEM SARAFOTONOM
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 1PROPRANOLOL ANTAGONIS RESEPTOR ADRENERGIK 1
ATROPIN ANTAGONIS RESEPTOR MUSKARINIK
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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
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HUBUNGAN DOSIS-RESPON
Graded dose-responses
Full agonist
Agonist concentration [A]
R e s p o n s e
One tissue/organ can yield the full response range
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•Emax & ED50
Log concentration [A]
R e s p o n s e
Emax
½ Emax
ED50 ED100 I I I I I I I I
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Therapeutic and Toxic Effects are
Dose-Related: Phenobarbital
Sleep Death
Dose of Phenobarbital
ED50 LD50
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Autonomic Pharmacology
Central Nervous System (CNS)
Peripheral Nervous System
Somatic Nervous System
Autonomic Nervous System (ANS)
Sympathetic Branch Parasympathetic Branch
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Autonomic Nervous SystemCharacteristics
“ F i g h
t o r F l i g h t ”
“ F e
e d or B
r e e d ”
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ANS Anatomy & Physiology
The nerves of the ANS exit the CNS andsubsequently enter specialized structurescalled “autonomic ganglia” Preganglionic fibers
Pass between the central nervous system and the
ganglia Postganglionic fibers
Pass between the ganglia and the effector organ
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Sympathetic versusParasympathetic
Sympathetic ganglia
Located close to the spinal cord or midwaybetween the spinal cord and the effectororgan
Parasympathetic ganglia Located close to or within the walls of the
target organs
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Cholinergic and AdrenergicFibers
Cholinergic Fibers that release acetylcholine
All preganglionic and postganglionic of theparasympathetic division
Adrenergic Fibers that release norepinephrine
Most postganglionic fibers of the sympatheticdivision are adrenergic, but some arecholinergic
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Neurochemical Transmission
No actual physical connection exists between
two nerve cells or between a nerve cell and theorgan it innervates Synapse
Space between nerve cells
Neruroeffector junction Specialized synapse between two nerve cells or a nerve
cell and an organ
Neurotransmitter Chemical messenger that conducts a nervous impulse
across a synapse
PREGANGLION POST GANGLION
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Neurotransmission
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Neurotransmitters
Acetylcholine
Preganglionic nerves of sympathetic nervoussystem
Preganglionic and postganglionic nerves of the parasympathetic nervous system
Norepinephrine
Postganglionic nerves of the sympatheticnervous system
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Acetylcholine
For cholinergic synapses acetylcholinemolecules combine with cholinergicreceptor molecules
Nicotinic Receptors
Produces an excitatory response Muscarinic Receptors
Produce an excitatory or inhibition, depending onwhere the target receptors are found
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Norepinephrine
For adrenergic synapses norepinephrinemolecules combine with adrenergicreceptor molecules
Alpha Receptors
Blood vessels Beta Receptors
Heart
Lungs
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