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FARMAKODINAMI

FARMAKODINAMI. Dr. dr. nurdiana, Mkes Lab. Farmakologi FKUB. DOSIS (R/). DOSIS YG DIMINUM. Faktor-2 FK A D M E. Fisiologik Patologik Genetik Umur Interaksi. KONSENTRASI OBAT DI TEMPAT KERJA. Faktor-2 FD reseptor homeostatik. EFEK / RESPON Px. terapeutik. toksik.

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FARMAKODINAMI

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

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

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

  4. 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

  5. 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

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

  7. 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

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

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

  10. 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

  11. 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

  12. 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

  13. 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

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

  15. 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

  16. Agonis obat yang mampu berikatan dg reseptor dan menimbulkan efek (afinitas +, aktivitas intrinsik +) Antagonis obat yang mampu berikatan dg reseptor tetapitidak 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

  17. FUNCTIONAL ANTAGONISTS • Physiologic Antagonists • Chemical Antagonist

  18. 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

  19. 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.

  20. Polar Nonpolar Polar

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

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

  23. Classification Receptor Transduction Mechanisms • 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)

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

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

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

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

  28. Mechanism of beta-1 receptor activation in cardiac muscle

  29. Effect of beta-2 receptor activation on smooth muscle

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

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

  32. Speed of responses

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

  34. Agonist & Antagonist

  35. Agonist & Antagonist

  36. 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

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

  38. 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 Individual patient variations in drug responses

  39. 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

  40. 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

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

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

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

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

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

  46. 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

  47. Sympathetic versusParasympathetic • 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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