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Cardiac Glycosides: Part II(56 / 2 Handbook of Experimental Pharmacology / Cardiac Glycosides)

Cardiac Glycosides: Part II(56 / 2 Handbook of Experimental Pharmacology / Cardiac Glycosides)

          
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About the Book

The pharmacokinetics of digitalis glycosides have been the subject of extensive re- view (IISALO, 1977; ARONSON, 1980; PERRIER et ai., 1977). Research on glycoside kinetics has progressed at a rapid pace, requiring continuing reevaluation of the state of our understanding of this problem. The present article focuses on the effect of disease states (renal, gastrointestinal, thyroid, and cardiac) on the absorption, distribution, and clearance of a number of digitalis glycosides. Evidence is critically reviewed, and interpreted with respect to possible clinical implications. A. Renal Insufficiency I. Strophanthin Strophanthin disposition in renal failure has been evaluated in only two studies. KRAMER et ai. (1970) determined an elimination half-life of 14 h in normals as com- pared to 60 h in anuric patients. Similar results were reported by BRASS and Pm- LIPPS (1970) using tritiated strophanthin. They found a half-life value of 18 h in healthy individuals as compared to 68 h in anuric patients. The findings clearly in- dicate that the elimination half-life of strophanthin is prolonged in renal failure.

Table of Contents:
Pharmacokinetics - Distribution, Metabolism, and Elimination.- 1 Pharmacokinetics of Digitoxin.- A. Introduction.- B. Drug Uptake and Tissue Distribution.- I. Rate of Distribution and Distribution Half-Life.- II. Tissue Compartments and the Apparent Volume of Distribution.- III. Tissue Distribution.- IV. Passage Across Biologic Membranes.- 1. Blood-Brain Barrier.- 2. Placental Transfer.- C. Metabolism.- I. Basic Studies with Tissue Preparations and in Animals.- II. Single-Dose Studies in Humans.- III. Digitoxin Metabolism in Humans on Maintenance Treatment.- D. Enterohepatic Circulation.- E. Elimination and Excretion Pathways.- I. Serum Elimination Half-Life.- II. Serum Digitoxin Concentrations on Maintenance Treatment.- III. Excretion Pathways.- F. Modifications by Age.- I. Neonates, Infants, and Children.- II. Old Age.- G. Modifications by Disease States.- I. Gastrointestinal Disease.- II. Thyroid Disease.- III. Hepatic Disease.- IV. Renal Disease.- 1. Uremic Patients on Hemodialysis.- 2. Uremia Per Se.- 3. Nephrotic Syndrome.- H. Concluding Remarks.- References.- 2 Pharmacokinetics of Digoxin and Derivatives.- A. Tissue Distribution.- B. Apparent Distribution Volume.- C. Elimination.- I. Metabolism.- 1. Cleavage of Digitoxose Residues.- 2. Conjugation Reactions.- 3. Hydrogenation.- II. Excretion.- 1. Renal Excretion.- 2. Renal Excretion of Metabolites.- 3. Factors Influencing Renal Elimination.- 4. Extrarenal Excretion.- 5. Effect of Extrarenal Excretion on Bioavailability.- 6. Prediction of Digoxin Elimination.- 7. Acceleration of Digoxin Elimination.- References.- 3 Pharmacokinetics of Strophanthus Glycosides.- A. Introduction.- B. Enteral Absorption.- I. Human Investigations.- 1. Ouabain.- 2. Strophanthoside K.- 3. Cymarin.- 4. Cymarol.- 5. Helveticoside Derivatives.- II Animal Experiments.- 1. Ouabain.- 2. Strophanthoside K.- 3. Cymarin.- 4. Convallatoxin.- 5. Other Derivatives of Strophanthidin K.- C. Blood Level and Tissue Distribution.- I. Human Investigations.- 1. Ouabain.- 2. Strophanthoside K.- 3. Acetylstrophanthidin.- II. Animal Experiments.- 1. Ouabain.- 2. Strophanthoside K.- 3. Cymarin.- 4. Convallatoxin.- D. Metabolism.- I. Human Investigations and Animal Experiments.- 1. Ouabain.- 2. Strophanthidin K Derivatives.- E. Excretion.- I. Human Investigations.- 1. Ouabain.- 2. Strophanthoside K.- 3. Cymarin.- 4. Acetylstrophanthidin.- II Animal Experiments.- 1. Ouabain.- 2. Strophanthoside K.- 3. Cymarin.- 4. Acetylstrophanthidin.- 5. Dihydroouabain.- 6. Convallatoxin.- F. Conclusions.- References.- 4 Pharmacokinetics of Squill Glycosides.- A. Introduction.- B. Distribution After Intravenous and Oral Administration.- I. Proscillaridin A.- II. Meproscillarin.- C. Metabolism and Excretion Pathways.- I. Proscillaridin A.- II. Meproscillarin.- D. Elimination Rate.- I. Proscillaridin A.- II. Meproscillarin.- References.- Pharmacokinetics - Additional Pharmacokinetic Parameters of Cardiac Glycosides.- 5 Plasma Protein Binding of Cardiac Glycosides.- A. Introduction.- B. Characterization of Plasma Protein Binding.- C. Role of Albumin Binding in Pharmacokinetics.- D. Conclusion.- References.- 6 Intestinal Absorption and Secretion of Cardiac Glycosides.- A. Introduction.- B. Intestinal Absorption of Cardiac Glycosides.- I. Dependence on Polarity.- 1. Results Compatible with Diffusion.- a) Natural Glycosides.- b) Semisynthetic Glycosides.- 2. Results Incompatible with Diffusion.- II. Dependence on Dose.- 1. Results Compatible with Diffusion.- 2. Results Incompatible with Diffusion.- III. Dependence on Inhibitors.- 1. Results Compatible with Diffusion.- 2. Results Incompatible with Diffusion.- IV. Dependence on Time.- 1. Results Compatible with Diffusion.- 2. Results Incompatible with Diffusion.- V. Dependence on Blood Flow and Lymph Drainage.- C. Intestinal Secretion of Cardiac Glycosides.- I. Secretion by the Isolated Mucosa of Guinea Pig Jejunum.- II. Secretion by the Isolated Mucosa of Guinea Pig Ileum and Colon.- III. Secretion by the Isolated Mucosa of Human Intestine.- IV. Intestinal Secretion of Glycosides in Vivo.- V. Comparative Aspects of Intestinal Glycoside Secretion.- D. A Concept for the Intestinal Permeation of Cardiac Glycosides.- E. Conclusions.- References.- 7 Cardiac Uptake and Binding of Cardiac Glycosides.- A. Introduction.- B. Experimental Approaches.- C. Uptake of Radiolabeled Cardiac Glycosides by Superperfused Cardiac Preparations.- I. General Characteristics and Kinetic Properties.- II. Characteristics of Uptake in Relation to Rate of Stimulation.- D. Uptake of Cardiac Glycosides by Perfused Cardiac Preparations.- I. Gross Cardiac Uptake of Cardiac Glycosides in Relation to their Effects.- II. Kinetic Properties of Cardiac Glycoside Extraction by Cardiac Preparations.- III. Translocation of Cardiac Glycosides from their Initial Site of Interaction.- IV. Characteristics of Microsomal Cardiac Glycoside-Binding Sites.- 1. Microsomal Content in Relation to Pharmacologic Effect.- 2. General Kinetic Considerations.- 3. Species Differences.- 4. Agents that Reduce the Microsomal Content of Cardiac Glycosides.- E. Binding of Cardiac Glycosides to Fragmented Cardiac Membranes.- F. Summary.- References.- 8 Bioavailability of Cardiac Glycosides.- A. General Aspects.- B. Methods of Measurement.- C. Digoxin Tablets.- D. Other Digoxin Formulations.- E. Other Cardiac Glycosides.- I. Digitoxin.- II. Lanatoside C.- III. Methyldigoxin and Acetyldigoxin.- F. Effect of Nonbiopharmaceutical Factors.- I. Impairment by Drug Interaction.- 1. Neomycin.- 2. Sulphasalazine.- 3. Diphenylhydantoin.- 4. p-Amino salicylic Acid.- 5. Antacids.- 6. Anion-Exchange Resins.- 7. Activated Charcoal.- II. Gastrointestinal Disease.- G. Conclusions.- References.- 9 Pharmaceutical Quality Control Standards for Cardiac Glycosides.- A. Introduction.- B. Cardiac Glycoside Preparations in Clinical Use.- C. Quality Control Standards and Test Procedures.- I. Bulk Drug.- 1. Description and Solubility.- 2. Identity Tests.- 3. Specific Optical Rotation.- 4. Assay Methods.- a) Biologic.- b) Chemical Assays.- c) Presence of Foreign Substances.- d) Loss on Drying.- e) Ash.- f) Microbial Tests.- II. Pharmaceutical Preparations.- 1. Injections.- 2. Elixirs/Tinctures/Solutions.- a) Elixirs.- b) Tinctures.- c) Solutions.- 3. Tablets and Capsules.- a) Tests for Identity and Assay.- b) Physicochemical Test Requirements for Solid Dosage Products.- III. General Pharmacopeial Tests Applied for Formulated Products.- IV. Product Stability.- V. The Future.- References.- Clinical Pharmacology.- 10 Effects of Cardiac Glycosides on the Failing and Nonfailing Heart.- A. Introduction.- B. Fundamental Positive Inotropic Action.- I. Failing Ventricle.- II. Normal Ventricle.- III. Diseased Nonfailing Ventricle.- IV. Atrial Myocardium.- C. Cardiac Energetics.- I. Normal Ventricle.- II. Failing Ventricle.- III. Coronary Artery Disease.- D. Acute Myocardial Infarction.- I. Failing Ventricle.- II. Diuretics and Nitrates.- III. Digitalis Mechanisms in Infarcted Ventricle.- E. Dose-Contractile Response Relationship.- F. Time Course of Contractile Action.- G. Unified Concept of Digitalis Cardiocirculatory Effects.- I. Failing Versus Normal Heart.- II. Digitalis Effectiveness Relative to Type of Heart Disease.- H. Conclusions.- References.- 11 The Effect of Disease on Cardiac Glycoside Pharmacokinetics.- Abstract/Summary.- A. Renal Insufficiency.- I. Strophanthin.- II. Ouabain.- III. Digoxin.- IV. Digitoxin.- 1. Absorption and Excretion.- 2. Protein Binding.- 3. Nephrotic Syndrome.- B. Gastrointestinal Disease.- I. Effect of Surgical Intervention on Digoxin Absorption and Excretion.- II. Effect of Abdominal Radiation Therapy on Digoxin Absorption and Excretion.- III. Malabsorption Syndrome.- IV. Absorption of Digoxin from the Colon in Normal Subjects and Patients with Colitis.- V. Kinetics of Digoxin and ?-Methyldigoxin in Patients with Acute Hepatitis and Cirrhosis.- VI. Pharmacokinetics and Metabolism of Digitoxin in Patients with Chronic Active Hepatitis.- VII. Kinetics of Digitoxin in Patients with Acute and Chronic Hepatic Insufficiency.- C. Thyroid Disease.- D. Cardiovascular Disease.- E. Conclusion.- References.- 12 Clinical Indications and Choice of Cardiac Glycosides, Clinical Conditions Influencing Glycoside Effects.- A. Indications for Glycoside Therapy.- I. General Considerations.- II. The Pathogenesis and Severity of Myocardial Insufficiency as Factors Governing the Indications for the Management of Digitalis Therapy.- III. Contraindications.- IV. Special Factors Governing the Indications for Glycoside Therapy in Various Heart Diseases.- 1. Mitral Stenosis.- 2. Chronic Cor Pulmonale.- 3. Angina Pectoris.- 4. Myocardial Infarction.- 5. Myocarditis.- 6. Hypertension.- B. Criteria of Adequate Glycoside Treatment.- I. Experimental Studies Under Clinical Conditions.- II. Clinical Criteria.- III. Interpretation of Serum Glycoside Measurements.- C. Guidelines for the Therapeutic Use of Glycosides.- I. Significance of the Pharmacological Data.- II. Misuse of the Pharmacological Data.- 1. Therapeutic Saturation Dose (Therapeutic Body Pool).- 2. Absorption.- 3. Elimination.- III. Dosage and Body Weight.- IV. Choice of Digitalis Glycoside.- V. Technique of Glycoside Administration.- VI. Alterations in Dosage Consequent on Changes in Glycoside Requirements.- 1. Dosage for Patients with Impaired Renal Function.- 2. Dosage for Patients with Impaired Hepatic Function.- 3. Hormonal. Factors.- D. Interactions.- E. Prophylactic Digitalization?.- F. Do Digitalis Glycosides Differ in Their Mode of Action?.- G. Digitalis Treatment in Infancy and Childhood.- H. Other Drugs Used in Conjunction with Digitalis for the Treatment of Heart Failure.- J. Strophanthin.- K. Meproscillarin.- References.- 13 Side Effects and Intoxication of Cardiac Glycosides: Manifestations and Treatment.- A. Introduction.- B. Electrophysiologic Properties.- I. Automaticity, Conduction, and Responsiveness.- II. Refractoriness.- III. Disorders of Impulse Formation.- IV. Disorders of Impulse Conduction.- V. Subcellular Basis of Toxicity.- C. Recognition of Toxicity.- I. Digoxin Pharmacodynamics.- II. Digitoxin Pharmacodynamics.- III. Digitalis Radioimmunoassay.- IV. Acetylstrophanthidin Tolerance Test.- V. Electrical and Vagal Stimulation Tests.- D. Conditions Affecting Toxicity.- I. Hypokalemia, Hypomagnesemia, and Alkalosis.- II. Hypercalcemia.- III. Hypoxemia, Stroke, and Renal Disease.- IV. Hormone and Related Influences.- V. Heart Disease.- VI. Patient Age.- VII. Atrial Fibrillation.- E. Potassium-Digitalis Interactions.- F. Quinidine-Digoxin Interactions.- G. Digitalis-Induced Arrhythmias.- H. Treatment of Toxicity.- I. Quinidine and Procainamide.- II. Lidocaine and Phenytoin.- III. Propranolol.- IV. Bretylium and Colestyramine.- V. Ventricular Pacemaker Overdrive.- VI. Rapid Right Atrial Pacing.- VII. Atrioventricular Block.- J. Conclusions.- References.- 14 Interactions Between Cardiac Glycosides and Other Substances in the Body.- A. Introduction.- B. Interactions with Cardiac Glycosides Influencing the Amount of Active Drug Available at the Site(s) of Action (Pharmacokinetic Interactions).- I. Interactions in the Gastrointestinal Tract.- 1. Chemical Interactions.- a) Hydronium Ion.- b) Enzyme Activity.- 2. Physical Interactions.- a) Activated Charcoal.- b) Anion-Exchange Resins.- c) Fibers and Bulk-Forming Agents.- d) Antacids and Antidiarrheals.- 3. Physiology Interactions.- a) Gastric Emptying Time and Intestinal Motility.- b) Damaged Mucosa.- II. Interactions with Systemic Drug Disposition.- 1. Plasma Protein Binding.- 2. Tissue Binding.- 3. Metabolism.- a) Hydroxylation.- b) Conjugation.- 4. Excretion.- a) Renal Excretion.- b) Biliary Excretion and Enterohepatic Circulation.- 5. Effects on Both Distribution and Elimination.- a) Potassium.- b) Spironolactone.- c) Quinidine.- d) Thyrostatic Agents and Thyroid Hormones.- C. Interactions with Cardiac Glycosides at the Receptor Level (Pharmacodynamic Interactions).- I. Substances Associated with Electrolyte and Acis-Base Balance.- 1. Ions Influencing Cardiac Function.- a) Potassium.- b) Magnesium.- c) Sodium.- d) Calcium.- e) Lithium.- 2. Acid-Base Balance.- 3. Diuretics.- a) Potassium-Depleting Diuretics.- b) Potassium-Sparing Diuretics.- 4. Miscellaneous Agents.- a) Insulin and Glucose.- b) Cathartics and Liquorice.- II. Drugs Known to Affect the Autonomic Nervous System.- 1. Sympathomimetic Amines.- 2. ?-Adrenoceptor Blocking Drugs.- 3. ?-Adrenoceptor Blocking Drugs.- 4. Adrenergic-Neuron Blocking Drugs.- 5. Cholinergie and Anticholinergic Drugs.- III. Antiarrhythmic Drugs.- 1. Group 1 Antiarrhythmic Drugs.- 2. Group 2 Antiarrhythmic Drugs.- IV. Other Drugs Used in Cardiovascular Therapy.- 1. Vasodilatating Drugs.- 2. Calcium Antagonists.- V. Miscellaneous Drugs.- 1. Doxorubicin.- 2. Thyrostatic Agents and Thyroid Hormones.- 3. Xanthines.- 4. Tricyclic Antidepressive Drugs.- 5. Drugs Used During Anesthesia.- D. Concluding Remarks.- References.- Author Index.


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Product Details
  • ISBN-13: 9783540109181
  • Publisher: Springer-Verlag Berlin and Heidelberg GmbH & Co. KG
  • Publisher Imprint: Springer-Verlag Berlin and Heidelberg GmbH & Co. K
  • Language: English
  • Returnable: N
  • Sub Title: Part II
  • ISBN-10: 3540109188
  • Publisher Date: 01 Nov 1981
  • Binding: Hardback
  • No of Pages: 394
  • Series Title: 56 / 2 Handbook of Experimental Pharmacology / Cardiac Glycosides
  • Weight: 955 gr


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