Farmacodynamics studies the biochemical and physiological effects of drugs, and their mechanisms of action. Most drugs produce effects by interacting with receptors on cells, leading to biochemical and physiological changes that constitute a characteristic response to the drug. The mechanism of action of drugs involves interaction with receptors like enzymes, ion channels, G-protein coupled receptors, and transcription factors. Understanding the structure-activity relationship of drugs is important for developing new drugs and synthesizing drugs with better therapeutic ratios or selectivity for certain tissues.
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Farmacodynamics studies the biochemical and physiological effects of drugs, and their mechanisms of action. Most drugs produce effects by interacting with receptors on cells, leading to biochemical and physiological changes that constitute a characteristic response to the drug. The mechanism of action of drugs involves interaction with receptors like enzymes, ion channels, G-protein coupled receptors, and transcription factors. Understanding the structure-activity relationship of drugs is important for developing new drugs and synthesizing drugs with better therapeutic ratios or selectivity for certain tissues.
Farmacodynamics studies the biochemical and physiological effects of drugs, and their mechanisms of action. Most drugs produce effects by interacting with receptors on cells, leading to biochemical and physiological changes that constitute a characteristic response to the drug. The mechanism of action of drugs involves interaction with receptors like enzymes, ion channels, G-protein coupled receptors, and transcription factors. Understanding the structure-activity relationship of drugs is important for developing new drugs and synthesizing drugs with better therapeutic ratios or selectivity for certain tissues.
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Download as PPT, PDF, TXT or read online from Scribd
Farmacodynamics studies the biochemical and physiological effects of drugs, and their mechanisms of action. Most drugs produce effects by interacting with receptors on cells, leading to biochemical and physiological changes that constitute a characteristic response to the drug. The mechanism of action of drugs involves interaction with receptors like enzymes, ion channels, G-protein coupled receptors, and transcription factors. Understanding the structure-activity relationship of drugs is important for developing new drugs and synthesizing drugs with better therapeutic ratios or selectivity for certain tissues.
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FARMAKODINAMIK
FARMAKODINAMIK:
Mempelajari efek biokimiawi dan fisiologi obat, serta mekanisme kerjanya Kebanyakan obat menimbulkan efek melalui interaksi dengan reseptornya pada sel organisme perubahan biokimiawi dan fisiologi yang merupakan respons khas untuk obat tersebut
MEKANISME KERJA OBAT
RESEPTOR
Komponen makromolekul fungsional yang dapat berinteraksi secara spesifik dengan obat/ligand. Agonis: (full agonist dan partial agonist)
obat yang efeknya menyerupai senyawa endogen
Antagonis:
obat yang menghambat kerja suatu agonis atau senyawa endogen
Agonis dengan efektivitas rendah efek maksimal lemah tetapi, dapat mengurangi efek maksimal yang ditimbulkan oleh agonis penuh
Agonis parsial / antagonis parsial:
Physiological receptors - Agonist - Antagonist - Negative / inverse agonist Binding of drugs to receptors - ionic - hydrogen - hydrophobic - van der Waals - covalent
Physiological receptors 1. Enzymes 2. Ion channels 3. G protein - coupled receptor systems 4. Transcription factors
Receptors I. Enzymes: - Tyrosine kinase: insulin, EGF, PDGF, lymphokines - Serine/threonine protein kinase: TGF - Guanylyl cyclase: ANF receptor, guanylin receptor - Tyrosine phosphatase II. Ligand-gated ion channels - Nicotinic Ach receptor - GABAA receptor - Glutamate, aspartate, glycine
III. G protein-coupled receptors - Biogenic amines - Eicosanoids - Peptide hormones Effectors: - Enzymes: adenylyl cyclase, PLA2, C, D - Ion channels: Ca++, K+, Na+ - Transport proteins IV. Transcription factors Cytosolic receptors: thyroid hormone, steroid, retinoid, vitamin D
G protein-coupled receptors
Plasma membrane-bound Ligands: biogenic amines, eicosanoids, peptide hormones Receptors-GTP binding to G proteins -- effector proteins Effector proteins : adenylyl cyclase, phospholipase A2, C, D, ion channels (Ca2+, K+, Na+), transport proteins G protein subunits a, , g
Associated with generation of second messenger
Ion (Na+, K+, Ca2+, Cl-)
Intracellular receptor
Nukleus
Ion channel receptor
NH2
Transkripsi gen
G protein-coupled receptor
I E PLC g a
II
III IV V
VI VI I a g
E AC
DAG + inositol trifosfat
ATP
cAMP
COOH
Transcription factors
Receptor : soluble DNA-binding protein
Steroids, thyroid, vitamin D, retinoids
The region nearest the carboxyl terminus binds hormone & serves a negative regulatory control The control region binds to nuclear DNA to inhibit or activate gene transcription
STRUCTURE ACTIVITY RELATIONSHIP
Struktur kimia suatu obat menetukan afinitasnya terhadap reseptor dan aktivitas intrinsiknya Perubahan kecil pada molekul obat, misalnya perubahan stereoisomer, dapat menimbulkan perubahan besar dalam sifat farmakologinya. Pengetahuan SAR penting dalam strategi pengembangan obat baru, sintesis obat yang rasio terapinya lebih baik, atau sintesis obat yang selektif terhadap jaringan tertentu.
Second messenger(s) cAMP cGMP Inositol trisphosphate, diacylglycerol Ca++ NO
Transmisi sinyal biologis dengan second messenger cAMP
Transmisi sinyal biologis dengan second messenger diasilgliserol (DAG) dan IP3 (inositol trifosfat)
a1-adrenoseptor
respons seluler protein kinase C fosforilasi protein
E = intensitas efek obat Emax = efek maksimal (aktivitas intrinsik) [D] = kadar obat bebas KD = konstanta disosiasi 1/KD = afinitas
HUBUNGAN KADAR / DOSIS INTENSITAS EFEK
E (% Emax)
E (% Emax)
[D]
(A)
(B) log [D]
HUBUNGAN DOSIS OBATPERSEN RESPONSIF
Distribusi frekuensi kumulatif (sigmoid)
Distribusi frekuensi normal
Indeks Terapi
Dosis terapi median atau dosis efektif median (=ED50) adalah dosis yang menimbulkan efek terapi pada 50% individu Dosis letal median (=LD50) ialah dosis yang menimbulkan kematian pada 50% individu, sedangkan TD50 ialah dosis toksik 50%. Indeks terapi merupakan parameter keamanan obat Indeks terapi = LD50/ED50 atau TD50/ED50
INDEKS TERAPI (= therapeutic window)
Contoh: obat hipnotik-sedatif
Indeks terapi =
LD50 ED50
ANTAGONISME FARMAKODINAMIK
Antagonisme pada reseptor, yaitu antagonisme melalui reseptor yang sama
1. 2.
Antagonisme kompetitif Antagonisme non kompetitif
Antagonisme fisiologik, yaitu antagonisme pada sistem fisiologik yang sama, tetapi pada sistem reseptor yang berlainan.
Antagonisme kompetitif.
Antagonis mengikat reseptor di tempat ikatan agonis (receptor site atau active site) secara reversibel Efek antagonisme dapat diatasi dengan meningkatkan kadar agonis tidak dapat diatasi dengan meningkatkan kadar agonis Ikatan antagonis secara ireversibel di receptor site maupun di tempat lain Ikatan antagonis pada komponen lain dalam sistem reseptor (reversible maupun ireversible)
Antagonisme nonkompetitif.
Actions of drugs not mediated by receptors
Binding to other molecules or ions : antacid Colligative effects : mannitol Structural analogs of biological chemicals : some antiviral & anticancer agents Desinfectants, detergent, alcohol, etc.
ISTILAH LAIN
Hiperreaktif:
respons berlebihan dg dosis rendah dosis tinggi sekali dibutuhkan untuk menimbulkan efek efek yang berhubungan dengan alergi obat.
Hiporeaktif:
Hipersensitif:
Supersensitif:
hiperreaktif akibat denervasi atau akibat pemberian kronik suatu bloker reseptor yang merupakan denervasi farmakologik.
ISTILAH LAIN
Toleransi:
Menurunnya respons akibat pajanan obat berulang-ulang jangka panjang. Toleransi yang terjadi dengan cepat setelah pemberian hanya beberapa dosis obat Efek aneh (bizarre)
