1. Absorption, Distribution, Metabolism and Elimination (ADME)

2. Drug Absorption
Dependant on route, MW (size), solubility, availability of carrier molecules, etc.
Wide variation in rate among different genetic backgrounds, and specific cases (ex.- percutaneous absorption through abraded skin).
Greatly affects how quickly a drug elicits its biological response.

3. Routes of Absorption Most common routes include:
Topical (influenced by blood flow, dermal thickness, lipid solubility)
Oral (dependant on pH, solubility, formulation, stability)
Rectal (wide variation in absorption, but useful in comatose patients, or if drug is easily destroyed by GI pH or digestive enzymes)
Pulmonary (rapid absorption of many compounds, also for local treatment)

4. Routes of Absorption Parenteral
Subcutaneous (under dermis, nonirritating drugs only, slow absorption)
Intramuscular (into muscle, nonirritating only, faster absorption, depot injections)
Intravenous (into vein, irritating drugs OK if given slowly, instant absorption)
Intra-arterial (into artery, good for local therapy)
Intrathecal (into CSF, bypassing BBB)

5. GI Absorption Curve

6. Absorption vs. Route

7. Membrane Permeability to Drugs

8. Membrane Permeability Based on Water Solubility

9. Permeability vs. Lipid Solubility

10. Absorption vs. Lipid Solubility

11. Intestinal Permeability Barrier

12. Diffusion vs. Partition Coefficient

13. pH vs. Absorption

14. Absorption via Endocytosis

15. Absorption via Gap Junctions

16. Tight Junctions

17. Capillary Permeability

18. Fenestrated Capillaries

19. CSF/Plasma Equilibrium

20. Lung Permeability

21. Tissue Permeability Summary

22. Distribution Phase following absorption.
Describes how a drug gets to it’s target tissue for action.
Influenced by solubility, body water, protein binding, tissue binding, specific carriers.

23. Distribution Total body water (easily accessible)
Intracellular ~ 40%
Extracellular ~ 20%
Interstitial ~ 15%
Vascular ~ 5%
Remainder in body fluids, bone, tendons, etc.

24. Disposition Pathways

25. Apparent Volume of Distribution

26. Protein Binding vs. Disposition

27. ADME Following IV Dosing

28. IV Bolus Distribution

29. Perfusion Rate vs. Distribution

30. Redistribution of Halothane

31. Metabolism and Elimination
How a drug gets removed (or changed) from body.
Most drugs metabolized to some degree.
Prodrugs utilize metabolism to form active compounds.
Two primary types of metabolism
Phase 1 (breakdown)
Phase 2 (synthetic)

32. Metabolism and Elimination
Metabolic Locations:
Liver
Lungs
Skin
Kidney
Blood
Most all other tissues to a small degree

33. Drug Disappearance Curve

34. Biotransformation Reactions

35. Metabolic Enzymes

36. Phenytoin Metabolism

37. Cytochrome P-450 (CYP)

38. Cytochrome P-450 (CYP) Reactions

39. Reduction Reaction

40. Phase 2 Glucuronidation

41. Phase 2 Glutathione Conjugation

42. Phase 2 Sulfate Conjugation

43. Miscellaneous Phase 2 Reactions

44. Nonmicrosomal Hydrolysis