بسم الله الرحمن الرحيم Pharmacology I for dental students

1. بسم الله الرحمن الرحيم Pharmacology I for dental students Course Description:It consists of course concerning the action of drugs on physiological and pathological processes with special emphasis on agents of special importance in the practice of dentistry. Dr. Mahmoud H. Taleb

2. Educational Objectives: • The student will gain knowledge in the principles of general pharmacology. The objectives will be for the student to be able to describe (1) Different families of therapeutic agents taken by or prescribed to dental patients in terms of clinical pharmacology, • (2) indication, usage, precautions, • (3) adverse reactions, • (4) over dosage absorption, • (5) metabolic rate, • (6) distribution, • (7) excretion Dr. Mahmoud H. Taleb

3. Competencies Addressed/Assurance of Competencies: • This course is designed to assure that students are familiar with the mechanisms of action and potential druginteractions/ contraindications of the medications that their patients are most likely to be taking when they seek dental care. Dr. Mahmoud H. Taleb

4. Course outline • Unit I . general principles of pharmacology • **Definitions and history of Pharmacology ** Drug nature, sources and dosage forms . • ** Receptors • ** Signal transmission and signal transduction • ** Dose response curve and pharmacokinetics • ** Pharmacogenetics • ** Adverse effects and drug toxicity. • ** Mechanism of drug action and factors affecting on it. • ** Dug laws and prescription writing Dr. Mahmoud H. Taleb

5. UNIT II. ANTI-INFECTIVES - Sulfonamides - Penicillins - Cephalosporins and relatedantibiotics -Tetracyclines, Macrolides, andLincosamides - Fluroquinolones and aminoglycosides - Miscellaneous Anti-infectives - Antitubercular Drugs - Leprostatic Drugs - Antiviral Drugs - Antifungal Drugs - Antiparasitic Drugs Dr. Mahmoud H. Taleb

6. UNIT III. DRUGS USED TO MANAGE PAIN - Nonnarcotic Analgesics: Salicylates and Nonsalicylates -Nonnarcotic Analgesics: Nonsteroidal Anti-inflammatory Drugs -Narcotic Analgesics -Narcotic Antagonists Dr. Mahmoud H. Taleb

7. UNIT IV. DRUGS THAT AFFECT THERESPIRATORY SYSTEM • Antihistamines and Decongestants Bronchodilators and Antiasthma Drugs Antitussives, Mucolytics, Expectorants Dr. Mahmoud H. Taleb

8. UNIT V. DRUGS THAT AFFECTTHE CARDIOVASCULAR SYSTEM • - Cardiotonics Drugs • - Antiarrhythmic Drugs • Antianginal and Peripheral Dilating Drugs • Antihypertensives • -Antihyperlipidemic Drugs Dr. Mahmoud H. Taleb

9. UNIT VI. DRUGS THAT AFFEC THE GASTROINTESTINALAND URINARY SYSTEMS - Diuretics - Drugs That Affect the Gastrointestinal System • UNIT VII. DRUGS THAT AFFECT THE HEMATOLOGICAL SYSTEM Anticoagulant and Thrombolytic Drugs Agents Used in the Treatment of Anemia Dr. Mahmoud H. Taleb

10. References • Pharmacology and Therapeutics for Dentistry, Needle and Yagilla • Lippincott's Illustrated Reviews: Pharmacology, 4th Ed • Basic and clinical pharmacology; Bertam Katzung • annual review article published in the Journal of the American Dental Association on the top 50 prescription medications dispensed in pharmacies for the previous year. • Color atlas of pharmacology, 2nd Ed. (by H. Lullmann et al., Thieme 2000, ISBN 0865778434) Dr. Mahmoud H. Taleb

11. Unit I. General principles What is pharmacology?Pharmacology can be defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. These substances may be chemicals administered to achieve a beneficial therapeutic effect on some process within the patient or for their toxic effects on regulatory processes in parasites infecting the patient. Such deliberate therapeutic applications may be considered the proper role of medical. Dr. Mahmoud H. Taleb

12. Pharmacology is not concerned primarily with what the drug may be used for, but with what actions it has , and what fate it encounters in the living organism. Dr. Mahmoud H. Taleb

13. Such deliberate therapeutic applications may be considered the proper role of medical pharmacology,which is often defined as the science of substances used to prevent, diagnose, and treat disease. Dr. Mahmoud H. Taleb

14. Toxicologyis that branch of pharmacology which deals with the undesirable effects of chemicals on living systems, from individual cells to complex ecosystems. Dr. Mahmoud H. Taleb

15. WHAT IS A DRUG? • A drug can be defined as a chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. e.g. Vit C, penicillin, LSD, hydrocortisone Dr. Mahmoud H. Taleb

16. Drugs may be ( Plant sources, animal sources, mineral sources or synthetic) • -- synthetic chemicals,e.g. aspirin - chemicals obtained from plants or animals. • - products of genetic engineering. • A medicine is a chemical preparation, which usually but not necessarily contains one or more drugs, administered with the intention of producing a therapeutic effect. Dr. Mahmoud H. Taleb

17. DrugNomenclature • - Chemical name • - Nonpropietary drug name( generic name). • Propietary drug name ( trade name). • Common name. Dr. Mahmoud H. Taleb

18. Dr. Mahmoud H. Taleb

19. Medicines usually contain other substances (excipients, stabilisers, solvents, etc.) besides the active drug, to make them more convenient to use. To count as a drug, the substance must be administered as such, rather than released by physiological mechanisms. Many substances, such as insulin or thyroxine, are endogenous hormones but are also drugs when they are administered intentionally. Dr. Mahmoud H. Taleb

20. Dr. Mahmoud H. Taleb

21. Figure 1.1 Schematic representation of drug absorption, distribution, metabolism, and elimination. Dr. Mahmoud H. Taleb

22. The chief aspects of pharmacology includes: • *** Pharmacokinetics: kinetics of ADME • *** Pharmacodynamics: study biochemical, pharmacological effect of drugs & their mechanism of action. • *** Pharmacotherapeutics: proper selection &use of drugs ( pharmacology of drugs----- physiology & pathology of disease). Dr. Mahmoud H. Taleb

23. Dose of drug Drug conc in target organ ADME • Receptor binding Mechanism & Therapeutic effect of drug Dr. Mahmoud H. Taleb

24. Mechanism of drug action • 1- physically e.g. adsorption • 2- chemically e.g. neutralization • 3- Action on enzymes e.g. acetozolamide • 4- action on cell membrane e.g. procaine • 5- Interferance with normal metabolic pathway e.g. sulphonamide • 6- Action on cell receptor e.g. most common drugs Dr. Mahmoud H. Taleb

25. The dosage of drugs • Therapeutic dose. • Maximal tolerated dose. • Initial dose. • Maintenance dose • Lethal or fatal dose. Dr. Mahmoud H. Taleb

26. Drug standard & references • The definition and standardization of drugs are regulated by law in term of name, purity, potency, preparation and disribution to the public. • The standards are published in pharmacopoeias. • A drug listed in pharmacopoeia is termed an “ official”. Dr. Mahmoud H. Taleb

27. Other sources of information • There are other sources of information as scientific journals • * Drugs • * Pharmacological Reviews • * British Journal of Pharmacology • *Biochemical Pharmacology • * Pharmacy & Pharmacology Dr. Mahmoud H. Taleb

28. Factors modifying the dosage and action of drugs • 1-Age, weight & BSA Child require smaller dose. 2- Sex • Female require smaller dose • Female pass during pregnancy, labour and lactation. 3- Route of administration. 4- Time of administration 5- Drug intolerance 6- Drug allergy 7- Tolerance Dr. Mahmoud H. Taleb

29. 8- Pathological state 9- Accumulation 10- Emotional factors 11- Genetic abnormalities 12- Drug interactions 13- Drug toxicity 14- Drug dependence Dr. Mahmoud H. Taleb

30. Drug ToxicityKnowledge of toxic effects of drug is of importance indetermining their safety. Before a new drug is introduced clinically, it is usually subjected to a variety of a animal toxicity tests. Animal toxicity studies The acute toxicity of drugs is usually measured by the median lethal dose or LD50 will vary according to many factors. Therapeutic index This is the ratio of LD50/ED50 . The therapeutic index is a good guide to the safety of a drug.The higher the index, the safer is the drug. Dr. Mahmoud H. Taleb

31. Toxic effect of drug in man The toxicity of therapeutic agents in man may be due to any of the following causes: 1- overdose 2- Allergy 3- Teratogenicity 4-Intolerance 5- Secondary effects 6- Production of disease 7- Iodiosyncrasy Dr. Mahmoud H. Taleb

32. 8- Hepatotoxicity 9- Nephrotoxicity 10- Nerve damage 11- Hematological toxicity 12- Drug dependance 13- Carcinogenesis 14- Drug interaction Dr. Mahmoud H. Taleb

33. Drug dependence It is a phenomenon which is related to tolerance , It may either take the form of habituation or addiction. Where continued presence of the drug is required for normal function is called physical dependence, which is defined as signs& symptoms make withdrawal symptoms or abstinence syndrome. Addiction. e.g. morphine, tramadol, barbiturates Habituation e.g. tea Dr. Mahmoud H. Taleb

34. Drug interaction 1- Synergism 2- Potentiation 3- Addition 4- Antagonism Dr. Mahmoud H. Taleb

35. Classification of drug interaction Consequence 1- Beneficial ( enhancement of therapeutic effectiveness , or diminished of toxicity). 2- Adverse ( diminished of therapeutic effectiveness or enhancement of toxicity0. Dr. Mahmoud H. Taleb

36. Site of interaction • External ( Physicochemical incompatibility • Internal This can be a body site or system e.g. GIT, Liver) or the site of drug action e.g.cell membrane, receptor. Dr. Mahmoud H. Taleb

37. Mechanism Pharmacodyanmic interaction: refers to drug-induced changes in the effects of other drugs. Pharmacokinetic interaction: change in the pharmacokinetics of one drug introduced by another drug ADME Dr. Mahmoud H. Taleb

38. Absorption Physicochemical interaction Altered gastrointestinal motility Change in bacterial flora Mucosal damage Distribution Blood flow Serum binding Tissue binding Dr. Mahmoud H. Taleb

39. Dr. Mahmoud H. Taleb

40. Drug Receptor and Pharmacodynamics Definition of receptors: A range of different biological components that may serve as binding sites , mediating the actions of drugs or chemical reactive area on cell and as a result produce biological action e.g. enzymes They are targets of drug action that may be protein in nature, and these include lipids, ions, and water. Dr. Mahmoud H. Taleb

41. Receptor Mechanistic concept 1- Receptors are membrane protein, have more one subtypes of binding site. 2- Binding of compound for the receptor result in activation of the receptor and transmission of a signal to intracellular side. 3- The magnitude of transmembrane signal may depend on the % of available receptor that are occupied or rate of occupancy. Dr. Mahmoud H. Taleb

42. Drug interaction with specific receptors ** Intetaction of a drug with a receptor involve various types of chemical forces ( electrostatic forces, hydrogen bonds. Vandervals forces)…. with molecular complementarily with fitness of molecular shape and location. ** Minor alteration of the drug molecule , alter the ability of the drug to bind to the receptor ( Stereoselective). Dr. Mahmoud H. Taleb

43. Drug receptor binding Affinity of a receptor for a drug can be measured and the index of this affinity referred to association constant Ka D + R → DR → effect K1 → rate of binding k2 → rate of dissociation Association constant = K1/ k2 =Ka Dissociationconstant =K2/ k1 =Kd • The value of Kd can be used to determine the affinity of a drug for its receptor. Affinity describes the strength of • the interaction (binding) between a ligand and its receptor. The higher the Kd value, the weaker the interaction • and the lower the affinity. Dr. Mahmoud H. Taleb

44. Effect of drug on receptor • Agonists: If a drug binds to a receptor and produces a biologic response that mimics the response to the endogenous ligand, it is known as an agonist. For example, phenylephrine is an agonist at α1-adrenoceptors, • because it produces effects that resemble the • action of the endogenous ligand,norepinephrine. Dr. Mahmoud H. Taleb

45. Upon binding to α-adrenoceptors on the membranes of vascular smooth muscle, phenylephrine mobilizes intracellular Ca2+, causing contraction of the actin and myosin filaments. The shortening of the muscle cells decreases the diameter of the arteriole, causing an increase in resistance to the flow of blood through the vessel. Blood pressure therefore rises to maintain the blood flow. • All of these actions are attributable to interaction • of the drug molecule with the receptor molecule. In general, a full agonist has a strong affinity for its receptor and good efficacy. Dr. Mahmoud H. Taleb

46. Antagonists: Antagonists are drugs that decrease the actions of another drug or endogenous ligand. Antagonism may occur in several ways. • Many antagonists act on the identical receptor macromolecule as the agonist. • Antagonists, however, have no intrinsic activity and, therefore, produce no effect by themselves. Although • antagonists have no intrinsic activity, they are able to bind avidly to target receptors because they possess strong affinity. • If both antagonist and agonist bind to the same site on the receptor, they are said to be competitive Dr. Mahmoud H. Taleb

47. Dr. Mahmoud H. Taleb

48. Dr. Mahmoud H. Taleb

49. Figure 2.2 Transmembrane signaling mechanisms. A. Ligand binds to the extracellular domain of a ligand-gated channel. B. Ligand binds to a domain of a serpentine receptor, which is coupled to a G protein. C. Ligand binds to the extracellular domain of a receptor that activates a kinase enzyme. D. Lipid-soluble ligand diffuses across the membrane to interact with its intracellular receptor. Dr. Mahmoud H. Taleb

50. Drug solubility and Absorption Routes of drug administration. Choice of route…. Must depend on therapeutic objectives Dr. Mahmoud H. Taleb