2. PHARMACOLOGY INTRODUCTION Lecture one

3. Introduction What is pharmacology? Why do we need to take pharmacology? Significance of pharmacology to Dentistry

4. History of Pharmacology In 1897, Felix Hoffman, a research chemist employed by the "Farbenfabrikin vorm. Freidr. Bayer and Co." synthesized acetylsalicylic acid. On February 1, 1899, Aspirin ® was registered as a trademark. On March 6 th of the same year, this drug was registered with the Imperial Patent Office in Berlin. Aspirin quickly become popular worldwide, and remains an important drug today. (Interestingly, it was not until 1971 that Sir John Vane discovered the mechanism of action of aspirin, a feat that earned him the 1981 Nobel Prize for Medicine.)

5. Pharmacology DEFINITIONS: Pharmacology : is the science dealing with interactions between chemicals ( drugs ) and living systems. pharmakol : medicine Logia: study

6. DEFINITIONS: Drug: chemical substances that, when introduced into the body, alters the body's function by interactions at the molecular level. Prodrug: a chemical that is readily absorbed and distributed and then converted to the active drug by biologic processes — inside the body.

7. DEFINITIONS: Medical pharmacology : is the science of materials used to prevent, diagnose, and treat disease. Toxicology : IS that branch of pharmacology that deals with the undesirable effects of chemicals in biological system.

8. DEFINITIONS: Pharmacogenomics (or pharmacogenetics) is the study of the genetic variations that cause individual differences in drug response. Responses that are not found in the general population, such as general toxic effects, allergies, or side effects, but due to an inherited trait that produces a diminished or enhanced response to a drug. Differences in Enzyme Activity –Acetylation polymorphism –Butylcholinesterase alterations –Cytochrome P450 aberration

9. General Concepts Drug Dose Administration Drug Effect or Response Pharmaceutical Pharmacokinetics Pharmacodynamics Pharmacotherapeutics Disintegration of Drug Absorption/distribution metabolism/excretion Drug/Receptor Interaction

10. Pharmaceutical Phase -describes the stage during which the medication enters the body in one form and changes into another form to be utilized.

11. Pharmacokinetics Is what the body does to the drug. The magnitud of the pharmacological effect of a drug depends on its concentration at the site of action. Absorption Distribution Metabolism Elimination

12. Pharmacodynamics Is what the drug does to the body. Interaction of drugs with cellular proteins, such as receptors or enzymes, to control changes in physiological function of particular organs. Drug-Receptor Interactions –Binding Dose-Response –Effect Signal Transduction –Mechanism of action, Pathways

13. Drugs Drugs can be defined as chemical agents that uniquely interact with specific target molecules in the body, thereby producing a biological effect. Drugs can be stimulatory or inhibitory

14. How are Drugs Administered?

15. Routes of Drug Delivery Parenteral (IV) Inhaled Oral Transdermal Rectal Topical Parenteral (SC, IM)

16. Routes of Administration ENTERAL(GI route ) ORAL- most absorbed from small intestine. Pay close attention to presence or absence of food or antacid. Rectal - highly vascular-at times excellent site absorbs quickly. Sublingual- are valuable in administering drugs subject to a high degree of first-pass Metabolism.

17. Routes of Administration Parenteral route: IV, IM, SC most common –IV provides immediate availability –IM/SC-must rely on vascular system perfusion to site to be absorbed-if poor circulation use cautiously

20. The ROA is determined by the physical characteristics of the drug, the speed which the drug is absorbed and/ or released, as well as the need to bypass hepatic metabolism and achieve high conc. at particular sites ImportantInfo

21. No single method of drug administration is ideal for all drugs in all circumstances Very Important Info!

22. What Happens After Drug Administration? Drug at site of administration Drug in plasma Drug/metabolites in urine, feces, bile Drug/metabolites in tissues 1. Absorption 2. Distribution 4. Elimination 3. Metabolism

23. We are now talking about … Pharmacokinetics

24. Drug Absorption Absorption: is the process by which a drug enters the bloodstream without being chemically altered or The movement of a drug from its site of application into the blood or lymphatic system

25. Introduction Steps in appearance of intact drug in circulation pH = 1 - 3 pH = 5 - 7 disintegration disso- lution disso- lution absorption intestinal metabolism absorption hepatic metabolism clearancefaeces Pharmacological effect gastric emptying rate intestinal transit rate

26. Schematic diagram of an absorption membrane Lattice of protein Lattice of protein Inner lipoidal matrix Aqueous pores Hydrophilic tail Hydrophobic head

27. Mechanisms for drug transport across membranes

28. Pharmacokinetics I. Absorption A. Passive (simple) diffusion 1. Rate of transfer of substances are directly proportional to the concentration gradient on both sides of the membrane 2. Rapid for lipophilic, nonionic, small molecules 3. No energy or carrier required

29. Mechanisms of transport across the GIT/blood barrier A- Passive diffusion Drug in solution GIT fluidGIT membraneBlood Drug in solution carried away by blood h K1K1 K2K2 D (unionized concentration)

30. Pharmacokinetics B. Pore transport (Aqueous channels) 1. Small hydrophilic drugs (<200 MW) diffuse along conc gradient by passing through pores (aqueous channels) 2. No energy required

31. B_ Pore transport Intestinal lumen Apical cell membraneCell interior Drug Examples: water, urea, low weight sugars, organic electrolytes, etc. High concentration Lower concentration

32. Pharmacokinetics C. Facilitated diffusion – –drugs bind to carrier noncovalently. –No energy is required

33. Facilitated transport Intestinal lumen Apical cell membraneCell interior Drug Drug + Carrier CarrierDrug Carrier Examples: thymine etc. High concentration Lower concentration

34. Pharmacokinetics D. Active transport – identical to facilitated diffusion except that ATP (energy) powers drug transport against conc gradient

35. Active transport Intestinal lumen Apical cell membraneCell interior Drug Drug + Carrier CarrierDrug Carrier Examples: 5-fluorouracil, levodopa, riboflavine, body nutrients, l - amino acids, thiamine, nicotinic acid, vit B 6, etc. Higher concentration Low concentration ATP

36. Pharmacokinetics E. Pinocytosis and phagocytosis Engulfing of drug For large substances to enter the cells Ex: iron and vitamin B12 Each complexed with appropriate binding proteins

37. E- Pinocytosis Intestinal lumen Apical cell membraneCell interior Drug Not important for drug absorption High concentration Lower concentration vacoule

38. THAT ’ S IT!!