Presentation is loading. Please wait.

Presentation is loading. Please wait.

Pawitra Pulbutr B.Pharm (Hon), M.Sc. In Pharm (Pharmacology) Pharmacodynamics How drugs act: Molecular aspects Pharmacodynamics How drugs act: Molecular.

Similar presentations


Presentation on theme: "Pawitra Pulbutr B.Pharm (Hon), M.Sc. In Pharm (Pharmacology) Pharmacodynamics How drugs act: Molecular aspects Pharmacodynamics How drugs act: Molecular."— Presentation transcript:

1

2 Pawitra Pulbutr B.Pharm (Hon), M.Sc. In Pharm (Pharmacology) Pharmacodynamics How drugs act: Molecular aspects Pharmacodynamics How drugs act: Molecular aspects

3 Objectives อธิบายถึงเป้าหมายที่ยาออกฤทธิ์ที่สำคัญได้ อธิบายถึงกลไกการออกฤทธิ์ของยาผ่าน Receptor ชนิด Channel-linked receptor, G- protein receptor, Kinase-linked receptor และ Receptor that regulate gene transcription รวมทั้งความแตกต่างของการออก ฤทธิ์ผ่าน Receptors แต่ละชนิดได้ อธิบายถึงกลไกการออกฤทธิ์ของยาผ่าน Ion channel อธิบายถึงกลไกการออกฤทธิ์ของยาผ่าน Enzymes อธิบายถึงกลไกการออกฤทธิ์ของยาผ่าน Carrier molecules

4 Target for drug action Protein Receptors Ion channels Enzymes Carrier molecules Other :- Tubulin, DNA, RNA Chemotherapy >>> Anticancer, Antimicrobial

5 Receptors ตัวรับสัญญาณ ของเซลล์ เซลล์ ทำงานได้ สอดคล้อง กัน การสื่อสารกัน ระหว่างเซลล์ neurotransmitters, hormones, cytokines, growth factors สาร = Chemical messenger… neurotransmitters, hormones, cytokines, growth factors Receptor Chemical messenger

6 Ligand Drug (Agonist or Antagonist) Receptor Signal transduction Physiological response

7 Drugs act at receptor AgonistAntagonist Receptor activation Physiological response Block receptor No activation No Physiological response

8 Drugs act at receptor Receptor Receptor of chemical messenger in the body Receptor of specific drug Receptors are mostly named after their ligand.

9 Receptor classification by their localization Cell membrane receptor Cell membrane receptor Nuclear receptor or intracellular receptor Nuclear receptor or intracellular receptor Receptor families Channel linked receptor (Ionotropic receptor) G-protein coupled receptor (Metabotropic receptor, 7- transmembrane receptor) Receptor that regulate gene transcription Kinase linked receptor

10 Figure 2.1 Types of receptor-effector linkage

11 Channel linked receptor Nicotinic receptor … prototype Nicotinic receptor … prototype ACh … natural ligand ACh … natural ligand Ligand binding Channel lining One subunit 5 subunits 2  + 1  + 1  + 1  One receptor

12 G-protein coupled receptor (GPCR) o Cell membrane receptor o Single polypeptide chain o Muscarinic receptor o Adrenergic receptor o Dopamine receptor o 5-HT receptor o Opiate receptor o GPCR >>> Major drug target

13 G-protein coupled receptor Comprised of ….. 1. Extracellular N-terminal 2. 7-Transmembrane alpha helices 3. Intracellular C-terminal ligand binding Linked with “ G-protein ” Single peptide

14 Role of G-protein G protein “ free ” Effector molecule GTPase Second messenger production

15 Effector molecule or target protein 1. Membrane enzyme Adenylate cyclase Adenylate cyclase Phospholipase C Phospholipase C 2. Ion channels

16

17 Ligand G-protein coupled receptor Active G protein (  GTP) EnzymeIon channel Adenylate cyclase Phospholipase C cAMP IP 3 Increase intracellular calcium DAG Activate protein kinase C cAMP dep. Protein kinase phosphorylate enzyme Ion channel Open channel

18 Tyrosine kinase receptor/ Guanylate cyclase linked receptor Insulin receptor Insulin receptor Cytokine receptor *** Cytokine receptor *** Growth factor receptor *** Growth factor receptor *** Atrial natriuretic peptide receptor Atrial natriuretic peptide receptor Tyrosine kinase receptor Guanylate cyclase linked receptor

19 1. Extracellular domain 2. Transmembrane region 3. Intracellular domain Kinase linked receptor Ligand binding Single helix Catalytic domain (Enzyme activity)

20 Ras/ Raf pathway Ras = membrane protein

21 Jak/ Stat pathway Jak = cytosolic Tyrosine kinase Stat = transcriptional factor

22 Receptor that regulate gene transcription Intracellular receptor (Nuclear receptor) Intracellular receptor (Nuclear receptor) Lipophilic ligand Lipophilic ligand Steroid receptor, Thyroid receptor, Steroid receptor, Thyroid receptor, Vitamin A receptor, Vitamin D receptor Vitamin A receptor, Vitamin D receptor

23 Receptor Structure 1. DNA binding domain 2. Ligand binding domain 3. Transcription control domain Zinc finger Bind with DNA at response element

24 Peroxisome Proliferator Activated Receptor(PPARs) Nuclear receptor PPAR alpha, PPAR beta, PPAR gamma

25 Figure 2.1 Types of receptor-effector linkage

26 Receptor dynamics Desensitization Decrease response (decrease sensitivity) fast occur Phosphorylation of RC >>> Steric hindrance Receptor down regulation Decrease number of receptor slow occur … receptor internalization Prolonged agonist activation Decrease Response Tolerance

27 Receptor upregulation Increase number of receptor antagonist Prolonged antagonist blockade Over Response  -blocker (  -adrenergic receptor antagonist) May induce RC upregulation If sudden stop >>> Over response >>> hypertension Should be slowly stop the drugs

28 Ion channels Drugs which directly acting at ion channels 1. Block ion channels Physical properties Local anesthetics Block sodium channels See table 2.2

29 2. Bind with accessory site on ion channel Dihydropyridine Calcium channel blocker Benzodiazepine Chloride channel opening See table 2.2

30 Enzymes 1. Enzyme inhibitor Substrate analog Reversible Irreversible 2. False substrate Substrate analog Abnormal products See table 2.3

31 Carrier molecules

32 1.Inhibitors Inhibit carrier molecule function 2. False substrates False uptake See table 2.4

33 Target for drug action Protein Receptors Receptors Ion channels Ion channels Enzymes Enzymes Carrier molecules Carrier molecules Other :- Tubulin, DNA, RNA Chemotherapy >>> Anticancer, Antimicrobial

34 A, B, C, D, F


Download ppt "Pawitra Pulbutr B.Pharm (Hon), M.Sc. In Pharm (Pharmacology) Pharmacodynamics How drugs act: Molecular aspects Pharmacodynamics How drugs act: Molecular."

Similar presentations


Ads by Google