Pharmacology

1. Pharmacology Pharmacon = drug in Greek. -Logy = science. Pharmacology is the science that studies the effects of chemicals (drugs) on the living tissue.

2. Sources of drugs • Microorganisms as fungi & yeast e.g. penicillin’s • Plants e.g. digitalis. • Animals e.g. traditional insulin. • Synthetic in labs. e.g. sulfonamides. • Recombinant DNA technology & genetic engineering e.g. human insulin & growth factors.

3. Drug nomenclature: • Chemical name: • It indicates its atomic and molecular structure. • It may be given as a chemical formula or accompanied by diagram of its structure e.g. aspirin=acetylsalicylic acid C6H4COOHOCOCH3. • These names are of particular interest to the chemist & research . • Generic names • These names usually proposed by the company that first developed the drug. • E.g. generic name of acetylsalicylic acid is aspirin. • Generic name should be concise & it should signify a chemical derivation.

4. Trade names ( commercial or brand) • Are interchangeable terms used to identify the drugs manufactured by various drug companies. • Thus a specific generic drug may have many different trade names. e.g. Aspirin: ecotrin, bufferin, easparin.

5. Drug families: • Drugs may be classified according to one of the following: • 1-Chemical structure: e.g. barbiturates, &B-lactam. • 2-Mode of action: e.g. antacids, central nervous system stimulant. • 3-Physiological action: e.g. diuretics, anticholinergic • 4-Therapeutic effect: e.g. anticonvulsants, analgesics,…..

6. Toxicology • It is a branch of pharmacology that study harmful effects of chemicals on the biological system (environmental, economic, forensic are the major divisions of this science).

7. Chemotherapy: • Is a branch that deals with treatment of bacterial, fungal, viral, parasitic & malignant cells.

8. General pharmacology • Study Pharmacokinetics & Pharmacodynamics of drugs: • Pharmacokinetics: • Means what the body does to the drug. • It is the study of drug: • Absorption (A), • Distribution (D), • Metabolism (M) & • Excretion (E) ----ADME. • Pharmacodynamics: • Means what the drug does to the body. • It is the study of the mechanism of action & pharmacological effects of the drugs.

9. Pharmacology • The science that deals with drugs. • Pharmacokinetics of Drugs: Absorption, distribution, metabolism, and excretion. • Pharmacodynamics of Drugs: Drug actions, mechanism of action, and adverse effects of drugs.

10. Pharmacokinetics of Drugs

11. First, drug absorption from the site of administration (Absorption) permits entry of the therapeutic agent into plasma. • Second, the drug may then reversibly leave the blood stream and distribute into the interstitial and intracellular fluids (Distribution). • Third, the drug may be metabolized by the liver, kidney, or other tissues (Metabolism). • Finally, the drug and its metabolites are removed from the body in urine, bile, or feces (Elimination).

12. Schematic representation of drug absorption, distribution, metabolism, and elimination.

13. Commonly used routes of drug administration. IV = intravenous; IM = intramuscular; SC = subcutaneous.

14. Absorption of Drugs • Absorption is the transfer of a drug from its site of administration to the blood stream. Mechanisms of transport of drugs across cell membranes: 1. Passive diffusion: The driving force for passive absorption of a drug is the concentration gradient across a membrane separating two body compartments; the drug moves from a region of high concentration to one of lower concentration.

15. Continue…passive absorp. • The vast majority of drugs gain access to the body by this mechanism. • Lipid-soluble drugs readily move across most biologic membranes due to their solubility in the membrane bilayers.

16. 2. Facilitated diffusion: Other agents can enter the cell through specialized transmembrane carrier proteins that facilitate the passage of large molecules. • These carrier proteins undergo conformational changes allowing the passage of drugs or endogenous molecules into the interior of cells, moving them from an area of high concentration to an area of low concentration. • This process is known as facilitated diffusion. • This type of diffusion does not require energy, • can be saturated.

17. Schematic representation of drugs crossing a cell membrane of an epithelial cell of thegastrointestinal tract. ATP = adenosine triphosphate; ADP = adenosine diphosphate.

18. 3. Active transport: • A few drugs that closely resemble the structure of naturally occurring metabolites are actively transported across cell membranes using these specific carrier proteins. • This mode of drug entry also involves specific carrier. • Energy-dependentand is driven by the hydrolysis of adenosine triphosphate. • It is capable of moving drugs against a concentration gradient, that is, from a region of low drug concentration to one of higher drug concentration. • Shows saturation kinetics for the carrier.

19. 4. Endocytosis: This type of drug delivery transports drugs of exceptionally large size across the cell membrane. • Endocytosis involves engulfment of a drug molecule by the cell membrane and transport into the cell by pinching off the drug-filled vesicle. • For example, vitamin B is transported across the gut wall by endocytosis.

20. Effect of pH on drug absorption: Most drugs are either weak acids or weak bases. Acidic drugs (HA) release an H + causing a charged anion (A-). • However, the protonated form of basic drugs is usually charged, and loss of a proton produces the uncharged base (B). • Passage of an uncharged drug through a membrane. • A drug passes through membranes more readily if it is uncharged . • Thus, for a weak acid, the uncharged HA can permeate through membranes, and A cannot. • For a weak base, the uncharged form, B, penetrates through the cell membrane, but BH+ does not.

21. Continue…Effect of pH on drug absorption: • Therefore, the effective concentration of the permeable form of each drug at its absorption site is determined by the relative concentrations of the charged and uncharged forms. • The ratio between the two forms is, in turn, determined by the pH at the site of absorption and by the pka. (Henderson-Hasselbalch equation)

22. A. Diffusion of the non-ionized form of a weak acid through a lipid membrane. B. Diffusion of the nonionized form of a weak base through a lipid membrane.

23. This equation is useful in determining how much drug will be found on either side of a membrane that separates two compartments that differ in pH, for example, stomach (pH 1.0-1.5) and blood plasma (pH 7.4). [Note: The lipid solubility of the non-ionized drug directly determines its rate of equilibration.]