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FARMAKODINAMI Dr. dr. nurdiana, Mkes Lab. Farmakologi FKUB.

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Presentasi berjudul: "FARMAKODINAMI Dr. dr. nurdiana, Mkes Lab. Farmakologi FKUB."— Transcript presentasi:

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2 FARMAKODINAMI Dr. dr. nurdiana, Mkes Lab. Farmakologi FKUB

3 DOSIS (R/) DOSIS YG DIMINUM Faktor-2 FK A D M E KONSENTRASI OBAT DI TEMPAT KERJA Fisiologik Patologik Genetik Umur Interaksi Faktor-2 FD reseptor homeostatik EFEK / RESPON Px terapeutiktoksik

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

5 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

6 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

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

8 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

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

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

11 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

12 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

13 Definisi Effective Concentration 50% (ED 50 ) Concentration of the drug which induces a specified clinical effect in 50% of subjects Lethal Dose 50% (LD 50 ) Concentration of the drug which induces death in 50% of subjects

14 Definisi Therapeutic Index Measure of the safety of a drug Calculation: LD 50 /ED 50 Margin of Safety Margin between the therapeutic and lethal doses of a drug

15 Dose-Response Relationship Drug induced responses are not an “all or none” phenomenon Increase in dose may: Increase therapeutic response Increase risk of toxicity

16 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

17 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

18 FUNCTIONAL ANTAGONISTS 1. Physiologic Antagonists 2. Chemical Antagonist

19 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

20 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.

21 Polar Polar Nonpolar

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

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

24 Classification Receptor  Transduction Mechanisms 1. 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 kinases 4. Intracellular receptors (e.g. corticosteroids, thyroid hormone)

25 Transmembrane Signaling Mechanisms  = drug Out In   gene  P   G XY

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

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

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

30 Mechanism of beta-1 receptor activation in cardiac muscle

31 Effect of beta-2 receptor activation on smooth muscle

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

33 Intracellular Mechanism: Steroid Plasma   R Nucleus R  XXXXXXXXXXXXX RNA mRNA Protein Effects drug 

34 Speed of responses

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

36 Agonist & Antagonist

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38 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

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

40 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

41 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

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

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

44 E max & ED 50 Log concentration [A] Response E max ½ E max ED 50 ED 100 I I I I

45 Therapeutic and Toxic Effects are Dose-Related: Phenobarbital % Responding SleepDeath Dose of Phenobarbital ED50 LD50

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

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

50 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

51 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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53 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

54 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 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

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

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57 Neurotransmission

58 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

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

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

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