Pharmacology-Lecture-2024__2.pdf

1. Pharmacokinetics 2. Pharmacodynamics ƒ The study of the fate of drugs in the body : ƒ drug disposition= the way in which th the he b body...

1. Pharmacokinetics 2. Pharmacodynamics ƒ The study of the fate of drugs in the body : ƒ drug disposition= the way in which th the he b body ody handles han ndles d drugs rugss - A branch of pharmacology that focuses on the study of the biochemical and physiological effects of drugs and the mechanisms by which they produce such effects. ƒ Target Protein mediated mechanism ƒ Non Ȃ target protein mediated mechanism ƒ Colligative mechanism ± osmotic pressure ƒ Chemical reaction ƒ NEUTRALIZATION ƒ LOCAL ƒ SYST SYSTEMIC TEMIC ƒ CHELATION ƒ OTHERS ƒ CN + Sodium m tthiosulfate hiosulfate e ƒ Counterfeit incorporation mechanism SITES OF DRUG ACTION Target protein - biologic site of action of drugs Microtubule - important site of action Drugs that inhibit microtubule synthesis/ spindle protein Griseofulvin Vinca alkaloids Colchicine  ‰ mediates the transmission of endogenous chemical signals such as neurotransmitters, autacoids, and hormones. 1. Transports/Channels 2. Enzymes 3. Carrier Molecules 4. Receptors 20  1. Channels/transport Proteins that take part in transmembrane signaling and regulates ionic composition Voltage-gated Na channel Voltage-gated Ca channel e.g. drugs act on: Na channel- Local anesthetic,CBZ, PHENYTOIN Ca++ channel ± Ca++ channel blockers 2. Carrier molecules Na+-K+ ATPase pump - Digitalis glycosides (inhibitor) H+-K+ ATPase pump - PPI Na+-K+-2Cl- cotransport  3. Enzymes protein catalysts Xanthine oxidase - allopurinol Cyclooxygenase - NSAIDs ACE - ACE inhibitors MAO - MAOI Phenelzine Isocarbozaxid Tranylcypromine Acetylcholinesterase - Edrophonium COMT -ENTACAPONE,TOLCAPONE 4. Receptors Functional macromoleular components of cells with specific stereochemical configuration and in which a ligand interacts SPECIFICITY SELECTIVITY Ligand ± any chemical that has ability to bind to a receptor 1. Type I Receptor 2. Type II Receptor 3. Type III Receptor 4. Type IV Receptor  - Controls movement of ions - Found in cell membranes memb branes mulated in milliseconds - Stimulated Stim GABA A receptors receptors control con ntrol Cl Cl- iions ons -Benzodiazepines -Barbiturates -Barbitu uratess ¾Nicotinic receptors ‡ controls the entry of Na+ ‡ inhibited by neuromuscular blocker. Neurotransmitter IIons ons - G-protein linked receptor / metabotropic GTP ± binding signal transducer protein is G-Protein. G-protein modulates production of an intracellular second messenger. location: cell membrane onset: in seconds Examples of Type II receptors alpha receptors Beta receptors Muscarinic receptors ‰ Examples of G-proteins: ¾ Gs Ȃ stimulates adenylyl cyclase ¾ Gi Ȃ inhibits adenylyl cyclase ¾ Gq Ȃ increases IP3, DAG 30 Second messengers cyclic adenosine monophosphate (cAMP) cyclic guanosine monophosphate (cGMP) Inositol triphosphate (IP3) 3. Type III receptors/tyrosine kinases-linked receptors Tyrosine kinase - catalyze phosphorylation of tyrosine residues to modulate a number of biochemical processes  glucokinase glucose =====Îglucose-6-phosphate location: nucleus onset: hours  ‰ Examples: ¾Imatinib-gastrointestinal stromal tumors (GIST) ¾Gefitinib-epidermal growth factor receptor ¾Erythropoietin receptor ¾Receptor for Insulin ± utilization of glucose 34 4. Type IV receptor/gene transcription-linked receptors Central dogma -replication (DNA copied into complimentary DNA) -transcription (DNA template is copied to RNA) -translation (RNA synthesize protein) -location: nucleus/cytosol (cytoplasm) -onset: hours  Drugs that act on Type IV receptors ƒ Corticosteroids ƒ Mineralocorticoids ƒ Sex steroids ƒ Vitamin D ƒ Thyroid hormone