Mechanisms of Drug Interactions by Patrick F. D'ArcyMechanisms of Drug Interactions by Patrick F. D'Arcy

Mechanisms of Drug Interactions

byPatrick F. D'ArcyEditorJames C. McElnay, Peter G. Welling

Paperback | September 28, 2011

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Over the years a number of excellent books have classified and detailed drug­ drug interactions into their respective categories, e.g. interactions at plasma protein binding sites; those altering intestinal absorption or bioavailability; those involving hepatic metabolising enzymes; those involving competition or antagonism for receptor sites, and drug interactions modifying excretory mechanisms. Such books have presented extensive tables of interactions and their management. Although of considerable value to clinicians, such publica­ tions have not, however, been so expressive about the individual mechanisms that underlie these interactions. It is within this sphere of "mechanisms" that this present volume specialises. It deals with mechanisms of in vitro and in vivo, drug-drug, drug­ food and drug-herbals interactions and those that cause drugs to interfere with diagnostic laboratory tests. We believe that an explanation of the mechanisms of such interactions will enable practitioners to understand more fully the nature of the interactions and thus enable them to manage better their clinical outcome. If mechanisms of interactions are better understood, then it may be pos­ sible for the researcher to develop meaningful animal/biochemical/tissue cul­ ture or physicochemical models to which new molecules could be exposed during their development stages. The present position, which largely relies on patients experiencing adverse interactions before they can be established or documented, can hardly be regarded as satisfactory. This present volume is classified into two major parts; firstly, pharmacoki­ netic drug interactions and, secondly, pharmacodynamic drug interactions.
Title:Mechanisms of Drug InteractionsFormat:PaperbackDimensions:363 pages, 23.5 × 15.5 × 0.02 inPublished:September 28, 2011Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:3642646581

ISBN - 13:9783642646584

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Table of Contents

1 Introduction.- A. A Widening Problem.- I. Scope of This Present Volume.- B. Pharmacokinetic Drug Interactions.- I. Drug-Drug and Nutrient-Drug Interactions at the Absorption Site.- II. Drug Interactions at Plasma- and Tissue-Binding Sites.- III. Drug Interactions and Drug-Metabolising Enzymes.- IV. Interactions Involving Renal Excretory Mechanisms.- C. Pharmacodynamic Drug Interactions.- I. Drug-Drug Interactions at the Receptor and Other Active Sites.- II. Synergistic Interactions.- III. Drug Interactions In Vitro.- IV. Age and Genetic Factors.- V. Interference with Laboratory Testing.- VI. Herbal and Other Non-orthodox Medicines.- D. Comment.- I. Drug Interactions: Hazardous and Expensive Use of Resources?.- II. Sources of Information.- III. The Literature on Drug Interactions.- References.- Section I: Pharmacokinetic Drug Interactions.- 2 Drug Interactions in The Gastrointestinal Tract and Their Impact on Drug Absorption and Systemic Availability: A Mechanistic Review.- A. Introduction.- B. Physicochemical Interactions.- I. Complexation with Metal Ions.- II. Binding to Resins.- III. Complexation with Bile Salts.- IV. Nonspecific Adsorption.- C. Interactions with Drugs That Influence GI Motility and pH.- I. Alteration of Gastrointestinal Motility.- II. pH Alteration in the Gastrointestinal Tract.- D. Interactions Between Drugs That Share the Same Absorption Mechanism.- I. Passive Absorption.- II. Carrier-Mediated Absorption.- E. Interactions as a Function of Intestinal Metabolism.- F. Altered Absorption as a Result of Drug-Induced Mucosal Changes.- References.- 3 Drug-Food Interactions Affecting Drug Absorption.- A. Introduction.- I. Food.- II. Dosage Form.- B. Influence of Food on the Gastrointestinal Tract.- C. Direct Effect of Food on Drug Absorption.- D. Interactions Causing Reduced Drug Absorption.- E. Interactions Causing Delayed Drug Absorption.- F. Interactions Causing Increased Drug Absorption.- G. Interactions Causing Accelerated Drug Absorption.- H. Cases in Which Food Has No Effect on Drug Absorption.- I. Conclusions.- References.- 4 Drug Interactions at Plasma and Tissue Binding Sites.- A. Introduction.- B. Proteins Involved in Drug Binding.- C. Influence of Plasma and Tissue Binding on Drug Kinetics.- D. Displacement of Drugs from Binding Sites.- E. Therapeutic Consequences of Plasma Binding Displacement Drug-Drug Interactions.- I. Rapid Intravenous Infusion of Displacing Agent.- II. Parenteral Administration of Displaced Drug Having High Extraction Ratio.- III. Therapeutic Drug Monitoring and Drug Displacement from Plasma Binding Sites.- F. Therapeutic Consequences of Tissue Binding Displacement Interactions.- G. Displacement of Drugs from Binding Sites by Endogenous Materials.- H. Disease States and Altered Plasma Protein Binding.- I. Conclusions.- References.- 5 Drug Interactions and Drug-Metabolising Enzymes.- A. General Introduction.- B. Extrahepatic Microsomal Forms of Cytochrome P450.- C. Genetic Polymorphism.- D. Age and Disease and Cytochrome P450.- E. Clinical Importance of Enzyme Induction or Inhibition.- I. Enzyme Inducers.- II. Enzyme Inhibitors.- F. Conclusions.- References.- 6 Drug Interactions Involving Renal Excretory Mechanisms.- A. Introduction.- B. Mechanisms of Renal Excretory Clearance.- I. Anatomy and Physiology of the Kidney.- II. Glomerular Filtration.- III. Tubular Secretion.- 1. Physiological Considerations.- 2. Cellular Mechanisms.- 3. Pharmacokinetic Evidence for Tubular Secretion.- IV. Tubular Reabsorption.- C. Drug Interactions Involving Tubular Secretion.- I. Organic Anions.- 1. Probenecid.- 2. Methotrexate.- II. Organic Cations.- 1. Cimetidine.- 2. Ranitidine.- 3. Famotidine.- 4. Trimethoprim.- 5. Amiodarone.- 6. Quinine/Quinidine.- III. Organic Neutral Drugs.- 1. Digoxin.- D. Tubular Reabsorption.- I. Proximal Tubule Site.- 1. Lithium.- II. Distal Tubule/Collecting Duct Site.- 1. Urine pH and Flow Rate.- References.- Section II: Pharmacodynamic Drug Interactions.- 7 Drug-Drug Interactions at Receptors and Other Active Sites.- A. Introduction.- B. Mechanisms of Pharmacodynamic Interactions.- I. Transmitter Systems.- 1. Noradrenergic Synapse.- 2. Dopaminergic Synapse.- 3. Serotonergic Synapse.- 4. Cholinergic Synapse.- 5. GABAergic Synapse.- II. Ion Channels.- 1. Cardiac Ion Channels and Antiarrhythmic Drugs.- 2. Potassium Channels and Drug-Induced Torsades de Pointes.- 3. ATP-Sensitive Potassium Channels.- III. Hormonal Systems.- 1. Adrenal Corticosteroids.- 2. Glycaemic Regulation.- IV. Homeostatic Regulations.- 1. Renal Haemodynamics and Drug-Induced Acute Renal Failure.- 2. Prostaglandins, Natriuresis and Antihypertensive Therapy.- 3. Potassium Homeostasis.- References.- 8 Synergistic Drug Interactions.- A. Introduction: "Mithridatium".- B. Early Use of Probenecid with Penicillin.- C. Diuretic Combinations.- D. Co-trimoxazole.- E. Combination Treatment in Control of Epilepsy.- F. Antitubercular Drugs.- G. Anti-Leprosy Treatments.- H. Peptic Ulcer Therapy.- I. Non-Insulin-Dependent (Maturity Onset) Diabetes.- J. Cancer Chemotherapy.- K. Beneficial Interactions: A Philosophical Approach.- References.- 9 In Vitro Drug Interactions.- A. Introduction.- B. Incompatibility Interactions.- C. In Vitro Drug Interactions with Pharmaceutical Packaging and Intravenous Administration Equipment.- I. General Properties of Plastics.- II. General Properties of Glass.- III. Mechanisms of Interaction with Pharmaceutical Packaging.- 1. Sorption.- 2. Leaching.- 3. Permeation.- 4. Polymer Modification.- IV. Drug Interactions with Contact Lenses.- D. In Vitro Drug Interactions in Therapeutic Drug Monitoring and Drug Analysis.- I. Cyclosporin.- II. Chloroquine.- E. In Vitro Drug Interactions as a Result of Formulation Changes.- I. Problems with Sustained-Release Formulations.- II. Drug Excipient Interactions.- III. Formulation Effects on Rectal Bioavailability.- F. Conclusions.- References.- 10 Age and Genetic Factors in Drug Interactions.- A. Introduction.- B.Age.- I. Pharmacokinetics in the Elderly.- 1. Absorption.- 2. Distribution.- 3. Metabolism.- 4. Excretion.- II. Pharmacodynamics in the Elderly.- III. Inappropriate, Unnecessary and Interacting Medication.- IV. Logistics: Age and Medicine Consumption.- V. Long-Term Treatments.- C. Genetic Factors.- D. Comment.- References.- 11 Drugs Causing Interference with Laboratory Tests.- A. Introduction.- B. Mechanisms of Drug-Test Interactions.- I. Pharmacological Interferences.- 1. Effect on Glucose Determination.- 2. Effect on Uric Acid Determination.- 3. Intramuscular Injections and Muscle Enzyme Determination.- 4. Effect of Drug-Drug Interactions.- II. Methodological Interferences.- 1. Colorimetrie Interferences.- 2. Effect on pH of the Assay Environment.- 3. Interference with Chromatographic Methods.- 4. Interference with Enzymatic Reactions.- 5. Interference with Immunoassays.- C. Design of a Study for Evaluation of Analytical Interference.- D. Conclusions.- References.- 12 Drug Interactions with Herbal and Other Non-orthodox Remedies.- A. Introduction.- B. Animal Agents.- I. Fish Oil.- II. Chinese Toad Venom.- C. Amino Acids.- I. l-Tryptophan.- D. Vitamins.- E. Minerals.- F. Dietary Fads.- G. Herbal Drugs.- I. Effects of Herbal Drugs on Orthodox Drug Pharmacokinetics: Effects on Absorption.- 1. Dietary Fibres.- 2. Guar Gum.- 3. Tannins.- II. Effects of Herbal Drugs on Orthodox Drug Pharmacokinetics: Effects on Elimination.- 1. Cola Nut.- 2. Eucalyptus Species.- 3. Grapefruit Juice.- 4. Herbal Smoking Preparations.- 5. Kampo Medicines.- 6. Liquorice.- III. Effects of Orthodox Drugs on Herbal Drug Pharmacokinetics.- 1. Caffeine-Containing Herbs.- 2. Sparteine-Containing Herb.- 3. Teucrium chamaedrys.- IV. Pharmacodynamic Interactions Between Herbal Drugs and Orthodox Drugs.- 1. Betel Nut (Areca catechu).- 2. Garlic (Allium sativum).- 3. Karela (Momordica charantia).- 4. Liquorice (Glycyrrhiza glabra).- 5. Picrorhiza kurroa.- V. Multiple or Unclarified Interactions Between Herbal Drugs and Orthodox Drugs.- 1. Anthranoid Laxatives.- 2. Berberine.- 3. Ginseng (Pamax ginseng).- 4. Piperine.- 5. "Shankhapusphi".- 6. Yohimbine.- VI. Interactions Between Different Herbal Drugs.- H. Comment.- References.

Editorial Reviews

"The volume reflects the actual state-of-the-art and gives a good summary of what is currently known about drug interactions. The present volume is of interest not only to pharmacologists ... it should find a great number of interested readers among physicians." International Journal of Clinical Pharmacology, Therapy and Toxicology