El. knyga: Mechanisms of Drug Interactions

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.