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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

EFEK / RESPON Px
terapeutik

toksik

Fisiologik
Patologik
Genetik
Umur
Interaksi

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. dapat berupa efek farmakologi yang lain atau reaksi hipersensitif (alergi)  Efek toksik  efek obat yang tidak dikehendaki. sering merugikan. timbul pada dosis toksik/ supramaksimal .

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

1+1>2) Antagonis : Efek 2 macam obat yang berlawanan .    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.

LOCUS OF ACTION “RECEPTORS” Bound ABSORPTION Free TISSUE RESERVOIRS Free Bound Free Drug Bound Drug SYSTEMIC CIRCULATION BIOTRANSFORMATION EXCRETION .

EFEK OBAT INTERAKSI OBAT DENGAN RESEPTOR PADA SEL SUATU ORGANISME PERUBAHAN BIOKIMIAWI DAN FISIOLOGI RESPON (KHAS UTK MASING-MASING OBAT) .

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

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 Lethal Dose 50% (LD50)  Concentration of the drug which induces death in 50% of subjects .

Definisi  Therapeutic Index    Measure of the safety of a drug Calculation: LD50/ED50 Margin of Safety  Margin between the therapeutic and lethal doses of a drug .

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

Chemical Antagonist . Physiologic Antagonists 2.FUNCTIONAL ANTAGONISTS 1.

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

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 agonist’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.

Polar

Nonpolar

Polar

KANAL ION .IKT.IKT.RESEPTOR *RESEPTOR TRANSMEMBRAN . ENZIM . G-PROTEIN *RESEPTOR DI SITOSOL KOMUNIKASI SEL INTRA SEL ANTAR SEL .

IP3. DAG) EFEK BIOLOGI Komunikasi sel .TRANSDUKSI SINYAL MOLEKUL LIGAND 1ST messenger RESEPTOR ( TARGET SEL) EFEKTOR 2nd messenger (cAMP.

DAG Some receptors are themselves protein kinases Intracellular receptors (e. Transduction Mechanisms Ion channel linked receptors e. Ach nicotinic (Na+) and GABA (Cl-) G protein & second messenger generation. 3. guanylate cyclase .Classification Receptor  1. 4. 2.cGMP. thyroid hormone) .g. corticosteroids. phospholipase C IP3. adenylate cyclase stimulation or inhibition cAMP.g.

Transmembrane Signaling Mechanisms = drug  Out In    G  X Y P gene .

.

of second messenger of a G protein G prot regulation of an enzyme or ion channel Inactivation mechanism .Change in the Receptor activation cons.

DAG.The Major Effectors and Intracellular Second Messengers in GPCR Systems Effector adenylyl cyclase phospholipase C 2nd messenger cyclic AMP (cAMP) calcium. and phosphoinositide (IP3) .

Obat dan Efek D +R DR Efek agonis adr beta Gs   GDP  GTP ATP GDP Adenilat siklase GTP Enzim ATP cAMP R2C2 Protein kinase 2C ADPEnzim-PO4 EFEK 2R .

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 Plasma RNA mRNA R  R   drug .

Speed of responses .

Agonist vs antagonist Ag Ant + K+1 R K-1 Ag K+1 + R K-1 Ant Response .

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 .

obat Farmaseutik Farmakokinetik Farmakodinamik . lansia Interaksi : makanan.Faktor faktor yg mempengaruhi Farmakokinetik & Farmakodinamik Umur : bayi.

Individual patient variations in drug responses      Body weight and composition Age of client(young and old) Diet and Nutrition Ethnic origin Genetics     Pathophysiology(e g. 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 .

Al (OH)3 PERUBAHAN SIFAT OSMOTIK  DIURETIK OSMOTIKUREA.OBAT YANG BEKERJA TIDAK MELALUI RESEPTOR : PERUBAHAN ASAM BASAANTASIDA  Mg(OH)2. MANITOL GLISEROLMENGURANGI OEDEM SEREBRAL GANGGUAN FUNGSI MEMBRANANESTESI UMUMETER .

HUBUNGAN DOSIS-RESPON Graded dose-responses One tissue/organ can yield the full response range Response Full agonist Agonist concentration [A] .

•Emax & ED50 Response Emax ½ Emax I I I I ED50 I I I ED100 Log concentration [A] I .

% Respondin g Therapeutic and Toxic Effects are Dose-Related: Phenobarbital Sleep ED50 Death LD50 Dose of Phenobarbital .

.

Autonomic Pharmacology   Central Nervous System (CNS) Peripheral Nervous System   Somatic Nervous System Autonomic Nervous System (ANS)   Sympathetic Branch Parasympathetic Branch .

.

“Feed or Breed” “Fight or Flight” Autonomic Nervous System Characteristics .

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 Postganglionic fibers  Pass between the ganglia and the effector organ .

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 .

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

Keringat < ACH NIC < < NE alpha beta ACH NIC < D1 D ACH NIC < < EPINEPRINE SIMPATIS Otot jantung Ot. Darah Ginjal ADRENAL MEDULLA ACH NIC < VOLUNTARY MOTOR NERVE SOMATIC Otot rangka .PREGANGLION POST GANGLION PARASIMPATIS Otot jantung ACH NIC ACH MUS Otot polos < < Glandula MEDULLA ACH NIC ACH MUS < SPINALCORD SIMPATIS Kel.polos p darah SIMPATIS Pemb.

.

Neurotransmission .

Neurotransmitters  Acetylcholine    Preganglionic nerves of sympathetic nervous system Preganglionic and postganglionic nerves of the parasympathetic nervous system Norepinephrine  Postganglionic nerves of the sympathetic nervous system .

depending on where the target receptors are found .Acetylcholine  For cholinergic synapses acetylcholine molecules combine with cholinergic receptor molecules  Nicotinic Receptors   Produces an excitatory response Muscarinic Receptors  Produce an excitatory or inhibition.

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Norepinephrine  For adrenergic synapses norepinephrine molecules combine with adrenergic receptor molecules  Alpha Receptors   Blood vessels Beta Receptors   Heart Lungs .

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