University of Szeged Biopharmacy practice Editor: Árpád Márki, Ph.D. Authors: Árpád Márki, Ph.D. Adrienn Seres, Ph.D. Anita Sztojkov-Ivanov, Ph.D. Reviewed by: Szilárd Pál, Ph.D. Szeged, 2015. This work is supported by the European Union, co-financed by the European Social Fund, within the framework of "Coordinated, practice-oriented, student-friendly modernization of biomedical education in three Hungarian universities (Pécs, Debrecen, Szeged), with focus on the strengthening of international competitiveness" TÁMOP-4.1.1.C-13/1/KONV-2014-0001 project. The curriculum cannot be sold in any form! Contents Contents ...................................................................................................................................... 2 1. Definitions, routes of drug administration ............................................................................. 6 1.1. Definitions ....................................................................................................................... 6 1.2. Routes of drug administration ......................................................................................... 7 1.3. Questions ....................................................................................................................... 10 2. Receptors .............................................................................................................................. 11 2.1. Definitions ..................................................................................................................... 11 2.2. Characterization of receptors......................................................................................... 11 2.3. Classification of receptors ............................................................................................. 12 2.4. Questions ....................................................................................................................... 13 3. Dose vs. response curves ...................................................................................................... 14 3.1. Definitions ..................................................................................................................... 14 3.2. Standard dose vs. response curve .................................................................................. 15 3.2.1. Exercise 1 ............................................................................................................... 16 3.3. Semilogarithmic dose vs. response curve ..................................................................... 17 3.3.1. Exercise 2 ............................................................................................................... 18 3.4. Double reciprocal dose vs. response curve ................................................................... 18 3.4.1. Exercise 3 ............................................................................................................... 20 3.5. Specific activity ............................................................................................................. 21 3.6. Questions ....................................................................................................................... 22 4. Drug absorption .................................................................................................................... 23 4.1. Definitions ..................................................................................................................... 23 4.2. Factors affecting drug absorption .................................................................................. 23 4.3. Transport mechanisms during absorption ..................................................................... 23 4.4. Drug absorption from different sites ............................................................................. 24 4.4.1. Drug absorption from the oral cavity ..................................................................... 24 4.4.2. Drug absorption from the stomach ......................................................................... 24 4.4.3. Drug absorption from the intestines ....................................................................... 24 4.4.4. Pulmonary absorption ............................................................................................ 25 4.4.5. Transdermal absorption .......................................................................................... 25 4.4.6. Intramuscular and subcutaneous absorption .......................................................... 25 4.5. Questions ....................................................................................................................... 26 5. Distribution of drugs ............................................................................................................ 27 5.1. Volume of distribution .................................................................................................. 27 5.2. Factors influencing distribution .................................................................................... 27 5.2.1 The physicochemical properties of the drugs .......................................................... 27 5.2.2. The permeability of the membranes ....................................................................... 28 5.2.3. The effects of pH .................................................................................................... 29 5.2.4. The binding of the drugs to the tissues ................................................................... 29 5.2.5. The binding of the drugs to the plasma proteins .................................................... 30 5.3. Specialized distribution of drugs ................................................................................... 32 5.3.1. Distribution of drugs into the central nervous system (CNS) ................................ 32 5.3.2. The placental barrier ............................................................................................... 32 5.4. Exercises ........................................................................................................................ 33 5.5. Questions ....................................................................................................................... 37 6. Drug metabolism .................................................................................................................. 38 6.1. Definitions ..................................................................................................................... 38 6.2. Phases of drug metabolism ............................................................................................ 38 6.2.1. Phase 1 reactions .................................................................................................... 38 6.2.2. Phase 2 reactions .................................................................................................... 40 6.2.3. Phase 3 reactions .................................................................................................... 41 6.3. Exercise ......................................................................................................................... 41 6.4. Questions ....................................................................................................................... 43 7. Drug elimination .................................................................................................................. 44 7.1. Excretion of drugs ......................................................................................................... 44 7.1.1. Renal excretion ....................................................................................................... 44 7.1.2. Biliary excretion of drugs ....................................................................................... 46 7.1.3. Excretion in the saliva ............................................................................................ 46 7.1.4. Excretion in the breast milk ................................................................................... 47 7.1.5. Pulmonary excretion of drugs ................................................................................ 47 7.1.6. Excretion in the sweat ............................................................................................ 47 7.2. Multiple dosing - Exercise ............................................................................................ 47 7.2.1. Determination of the kinetic parameters of a drug ................................................. 48 7.2.2. Calculation of the maintenance dose of a drug ...................................................... 48 7.2.3. Administration of the loading dose ........................................................................ 48 7.3. Questions ....................................................................................................................... 49 8. Continuous infusion and multiple drug administration ........................................................ 50 8.1. Infusion .......................................................................................................................... 50 8.2. Multiple dosing ............................................................................................................. 53 8.3. Planning a continuous intravenous infusion .................................................................. 55 8.3.1. Calculation of the kinetic