Concepts in Biochemical Pharmacology: Part 1 by H.S. AckermannConcepts in Biochemical Pharmacology: Part 1 by H.S. Ackermann

Concepts in Biochemical Pharmacology: Part 1

byH.S. AckermannEditorBernard B. Brodie, James R. Gillette

Paperback | November 11, 2011

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This volume of the Handbook of Experimental Pharmacology (Concepts in Biochemical Pharmacology) will show that pharma­ cology has finally arrived as a true discipline in its own right, and is no longer the handmaiden of organic chemistry and physiology. Instead it is an amalgam of all the biological sciences including biochemistry, biophysical chemistry, physiology, pathology and clinical medicine. In the volumes that make up Concepts in Bioche­ mical Pharmacology we hope to convince Medical Schools what should now be obvious, that pharmacology is no longer that dull topic bridging the basic sciences with medicine, but is probably the most important subject in the medical curriculum. We are grateful for the advice of Dr. BYRON CLARKE, Director of the Pharmacology-Toxicology Program at the National Insti­ tutes of Health, whose support made possible much of the work described in this volume. Contents Section One: Routes of Drug Administration Chapter 1: Biological Membranes and Their Passage by Drugs. C. A. M. HOGBEN 1 References. . . . . . . . . . . . . . . . . . . . . . . . . . 8 Chapter 2: Absorption of Drugs from the Gastrointestinal Tract. L. S. SCHANKER. With 5 Figures. 9 I. Introduction. . . . . . . . . . . . . . . . . . . . . . . 9 II. Methods of Study. . . . . . . . . . . . . . . . . . . . . 9 III. Absorption from the Stomach . . . . . . . . . . . . . . . 11 IV. Intestinal Absorption of Non-Electrolytes and Weak Electrolytes 15 V. Absorption of Weak Electrolytes from the Colon and Rectum 18 VI. Intestinal Absorption of Organic Ions. . . . . . . . . . 19 VII. Intestinal Absorption of Macromolecules . . . . . . . . . . 19 VIII. Active Transport across the Intestinal Epithelium . . . . . 20 IX. Effect of EDTA on Drug Absorption from the Intestine . . . . . . .
Title:Concepts in Biochemical Pharmacology: Part 1Format:PaperbackDimensions:472 pages, 24.4 × 17 × 1.73 inPublished:November 11, 2011Publisher:Springer NatureLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:3642650546

ISBN - 13:9783642650543

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Table of Contents

Section One: Routes of Drug Administration.- 1: Biological Membranes and Their Passage by Drugs.- References.- 2: Absorption of Drugs from the Gastrointestinal Tract.- I. Introduction.- II. Methods of Study.- III. Absorption from the Stomach.- IV. Intestinal Absorption of Non-Electrolytes and Weak Electrolytes.- V. Absorption of Weak Electrolytes from the Colon and Rectum.- VI. Intestinal Absorption of Organic Ions.- VII. Intestinal Absorption of Macromolecules.- VIII. Active Transport across the Intestinal Epithelium.- IX. Effect of EDTA on Drug Absorption from the Intestine.- X. Physiological Factors and Dosage Forms of Drugs as Related to Absorption from the Gastrointestinal Tract.- References.- 3: Buccal Apsorption of Drugs.- A. H. Beckett.- R. D. Hossie.- A. General Considerations.- B. Administration of Drugs via the Buccal Route.- C. Buccal Absorption Characteristics of Drugs.- I. General Method for the Buccal Absorption Test.- II. Results of the Buccal Absorption Test.- III. Absorption of Basic Drugs.- IV. Absorption of Acidic Drugs.- V. Correlation with Partition Coefficients of Acidic and Basic Drugs.- VI. Kinetics of Buccal Absorption of some Acids and Bases.- D. Distribution and Excretion of some Basic Drugs after Buccal Absorption in Man.- References.- 4: Subcutaneous and Intramuscular Injection of Drugs.- A. Introduction.- B. Anatomy of Injections.- Local Events.- C. Mechanism of Absorption.- 1. Blood Flow Measurement.- 2. Absorption Kinetics.- 3. Pellet Absorption.- 4. Dynamic Events.- 5. Molecular Weight.- D. Biological Factors.- 1. Blood Flow.- 2. Connective Tissue.- 3. Glucocorticoids.- 4. Release of Biogenic Substances.- E. Injection Solutions.- 1. Injection Volume and Concentration.- 2. Tonicity.- 3. Hydrogen Ion Concentration.- F. Delayed Uptake.- 1. Prolonged Local Effect.- 2. Prolonged Systemic Effect.- G. Complications with Injections.- 1. Microbiological Contamination.- 2. Nerve Damage.- 3. Carcinogenesis.- H. Conclusion.- References.- 5: Absorption, Distribution and Excretion of Gaseous Anesthetics.- References.- 6: Aerosols.- I. Properties of Aerosols.- II. Measurement of Aerosols.- III. Generation of Aerosols.- IV. Deposition of Aerosols in the Respiratory Tract.- V. Absorption of Aerosols - Absorptive Surfaces.- VI. Absorption Studies.- VII. Summary.- References.- 7: Absorption of Drugs through the Skin.- A. Anatomy and Physiology.- I. Evolution.- II. Some Facts and Figures.- III. Anatomy.- 1. Epidermis.- 2. The Dermis (Corium).- 3. Subcutaneous Tissue.- 4. Appendages.- 5. pH.- IV. Dermatitis.- 1. Pathology.- 2. Structure Changes.- 3. Inflammation.- 4. Patterns.- B. Pathways of Percutaneous Absorption.- I. Introduction.- II. Alternate Pathways.- III. General Conclusions.- C. Factors Affecting Percutaneous Absorption.- I. Introduction.- II. Drug-skin Interactions.- 1. Skin Hydration.- 2. Circulatory Effects.- 3. Skin Metabolism.- 4. Binding of Drugs by Skin.- III. Vehicle-Skin Interactions.- 1. Effect on Skin Hydration.- 2. Temperature Effects.- 3. Solvent Effects.- IV. Drug-Vehicle Interactions.- 1. Release from Solutions.- 2. Release from Suspensions.- 3. Other Factors Influencing Release.- V. Drug-Vehicle-Skin Interactions.- 1. Diffusion Constant.- 2. Partition Coefficient.- 3. Drug Concentration.- VI. Summary.- D. Methods for Studying Percutaneous Absorption.- I. In Vitro.- 1. Diffusion Methods without a Membrane.- 2. Diffusion Methods with Membranes.- II. In Vivo.- 1. Animal Models.- 2. Remainder Analysis.- 3. Human Skin Window.- 4. Histology.- 5. Direct Observation.- 6. Systematic Observation.- 7. Dermal Perfusion.- E. Drugs and Methods for Percutaneous Absorption Studies.- F. Treatment.- I. Dermatologic Medications.- II. Anti-Inflammatory Agents - Topical Corticoids.- III. Vehicles.- References.- Section Two: Sites of Drug Transport and Disposition.- 8: The Nature of Drug-Protein Interaction.- A. Protein Structures.- B. Maintenance Forces of Protein Structure.- C. Protein Structure and Binding of Small Molecules.- I. Alterations of Structure at the Site of Binding of Small Molecules.- II. Alterations of Protein Structure at Sites Remote from the Binding Site of Small Molecules.- D. Forces in Protein-Small Molecule Interactions.- I. Bond Types.- II. "Hydrophobic Bonds".- III. Free Energy Considerations.- IV. Environmental Effects.- E. Albumins.- I. Structure of Albumin.- II. Albumin-Drug Interactions.- Conclusion.- References.- 9: Physical Methods for Studying Drug-Protein Binding.- A. Nonspectroscopic Techniques.- I. Rapid (or Kinetic) Dialysis.- II. Gel Filtration.- III. Heatburst Microcalorimetry.- B. Spectroscopic Techniques.- I. Ultraviolet and Visible Absorption Spectroscopy.- II. Fluorescence Spectroscopy.- III. Optical Rotatory Dispersion and Circular Dichroism.- IV. Nuclear Magnetic Resonance.- V. Other Spectroscopic Techniques.- VI. Stopped Flow and Relaxation Spectrometry.- References.- 10: Effect of Binding to Plasma Proteins on the Distribution, Activity and Elimination of Drugs.- A. Effect on Distribution and Activity.- 1. The Drug-Protein Complex.- 2. Tissue Distribution.- 3. Pharmacodynamic Activity.- 4. Antibacterial Activity.- 5. Entry into Transmembrane Compartments.- B. Effect on Elimination.- 1. Renal Excretion.- 2. Excretion into Bile.- 3. Salivary Excretion.- 4. Drug Metabolism.- C. Effect on Pharmacokinetics.- 1. A Model.- 2. Distribution.- 3. Kinetics.- D. Conclusions.- References.- 11: Competition between Drugs and Normal Substrates for Plasma and Tissue Binding Sites.- I. Introduction.- II. Bilirubin.- III. Thyroxine.- IV. Steroids.- V. Fatty Acids.- VI. Summary.- References.- 12: Drug Entry into Brain and Cerebrospinal Fluid With.- A. Introduction.- B. Anatomical Basis of Blood, Brain and CSF Barriers.- C. Blood-CSF Relationships.- D. CSF-Brain Relationships.- E. Drug Entry into CSF and Brain from Blood.- F. Methods for Studying Drug Entry and Exit.- G. Pathological Situations.- References.- 13: Translocation of Drugs into Bone.- I. Introduction.- II. The Nature of Bone.- III. Bone Mineral.- IV. Bone Mineral Dynamics and Ion Binding.- V. Binding of Heterogeneous Materials.- 1. Tetracyclines.- 2. Other Organic Drugs.- 3. Fluorides.- References.- 14: Translocation of Drugs and Other Exogenous Chemicals into Adipose Tissue.- Adipose Tissue as a Unique Body Compartment.- References.- 15: Placental Transfer of Drugs and their Distribution in Fetal Tissues.- I. Physicochemical Properties.- II. Maternal Hemodynamics and Pharmacokinetics.- 1. Maternal Hemodynamics.- 2. Maternal Pharmacokinetics.- 3. Special Considerations.- III. The Placenta.- 1. Anatomic Considerations.- 2. Hemodynamic Considerations.- 3. Other Considerations.- IV. The Fetal Circulation.- Practical Applications.- References.- 16: The Use of Autoradiography in Experimental Pharmacology.- A. Introduction.- B. Light Microscope Autoradiography.- I. Extracellular Space.- II. 3H Nicotine in Ganglia.- III. Estradiol in Uterine Tissue - Localization by Autoradiographic and Biochemical Techniques.- IV. 3H Estradiol in Nervous Tissue.- V. Neuromuscular Junction - Measurement of Active AchE Enzyme Sites in Endplates.- 1. Curare Alkaloids.- 2. Decamethonium.- 3. Diisopropylfluorophosphate (DFP).- C. Electron Microscope Autoradiography (EMAR).- I. DFP at Motor Endplates.- II. Norepinephrine at Sympathetic Nerve Terminals.- D. Organ and Whole Body Autoradiography.- References.- 17: Accumulation of Drugs at Sympathetic Nerve Endings.- A. Introduction.- B. Accumulation of Amines in Adrenergic Neurones.- C. Functional Significance of Amine Accumulation in Sympathetic Nerve Endings.- D. Effects on Norepinephrine Synthesis.- E. Chemical Sympathectomy with 6-Hydroxydopamine.- F. Uptake of Other Cyclic Bases.- Summary.- References.- Section Three: Sites of Drug Excretion.- 18: Excretion of Drugs by the Kidney.- I. The Components of the Renal Excretory System.- II. Assessment of Tubular Function.- III. Characteristics of Clearances Determined Mainly by Passive Processes.- IV. The Secretory System.- 1. Organic Anion Mechanism.- 2. The Organic Cation Mechanism.- 3. Other Components and Compounds Apparently Secreted by Two Mechanisms.- V. The Reabsorptive Systems: Bidirectional Transport.- VI. Analogous Aspects of Studies of Drug Metabolism and Excretion.- References.- 19: Excretion of Drugs in Bile.- A. Introduction.- B. Historical Aspects.- C. Types of Compounds Excreted in Bile.- D. Factors Involved in the Biliary Excretion of Chemicals.- I. Molecular Size.- II. Polarity.- 1. Polar Substances Excreted in Bile Unchanged.- 2. Compounds which are Excreted in Bile after Metabolism to a Polar Conjugate.- III. Molecular Structure and Biliary Excretion.- IV. Inter-Relationship of Molecular Size, Polarity and Structural Factors in Biliary Excretion.- E. Biliary Excretion of Quaternary Ammonium Compounds.- F. Biliary Excretion of Glycosides.- G. Mechanism of Excretion of Organic Compounds in Bile.- H. Biological Factors Influencing Biliary Excretion.- I. Binding to Plasma Proteins.- II. Metabolism.- III. Unusual Conjugates Found in Bile.- IV. Inter-Relationship of Urinary and Biliary Excretion.- V. Species Differences in Biliary Excretion.- 1. Biliary Excretion of Simple Mono- and Di-substituted Benzene Derivatives in Various Species.- 2. Biliary Excretion of Compounds of Molecular Size in the Range of 300-500 in Various Species.- 3. Biliary Excretion of Polar Compounds of Molecular Weight in the Range of 500-1000 in Various Species.- VI. Strain and Sex Factors in Biliary Excretion.- J. Pharmacological and Toxicological Implications of Biliary Excretion of Drugs.- I. Enterohepatic Circulation.- II. Metabolism by the Gut Flora.- References.- 20: Excretion of Drugs by Milk.- I. The Mammary Gland.- II. Distribution of Drugs in the Phases of Milk.- III. Passage of Drugs from Blood Plasma to Milk.- 1. Amount of Milk.- 2. Dependence on Drug Ionization.- 3. Experimental and Theoretical Ratios M. Ultr./P. Ultr..- 4. Active Excretion.- IV. Passage of Drugs from Milk to Blood Plasma.- V. Conclusion.- References.- 21: Extracorporeal and Peritoneal Dialysis of Drugs.- A. Introduction.- B. History of the Dialysis of Poisons.- C. Membrane Aspects of Drug Dialysis.- I. Peritoneal Dialysis.- II. Hemo or Extracorporeal Dialysis.- D. Problems in Methodology.- E. The Clinical Aspects of Dialysis of Drugs.- I. Antibacterials.- II. Sedatives and Tranquilizers.- III. Analgesics.- IV. Alcohol.- V. Other Foreign Compounds and Toxicants.- VI. Fluids and Electrolytes.- F. Summary.- References.- Author Index.