Allergic Reactions to Drugs

Section I: General Aspects of Drug Allergies.- 1 Immunochemical Basis of Allergic Reactions to Drugs.- A. Introduction.- I. Definitions.- II. Miscellaneous Parameters in Sensitization.- 1. Chemical Characteristics of the Antigen.- 2. Antigen Metabolism.- 3. Genetic Aspects.- B. Cellular and Immunochemical Elements in Antigenicity.- I. Cellular Aspects.- II. Antigenic Determinants Reacting with Antibody.- III. Antigenic Determinants in Cellular Reactions.- C. Antigenicity and Drugs.- I. Agents of Intrinsic Immunogenicity.- II. Low Molecular Weight Drugs as Immunogens.- 1. The Formation of Antigenic Determinants.- 2. The Formation of Complete Immunogens.- III. Immunogenic Complexes not Involving Covalent Linkage Between Hapten and Carrier.- IV. Molecular Parameters in Elicitation and Inhibition of Allergic Reactions.- References.- 2 Chemical and Pharmaceutical Aspects of Drug Allergy.- With 23 Figures.- A. Introduction: Routes of Formation of Drug Antigens.- B. Immunologically Active Macromolecular Contaminants of Penicillins.- C. Polymerization of ?-Lactam Antibiotics.- I. Penicillin Polymers.- 1. Formation and Structure of Polymers.- 2. Immunologic Effects of Polymers.- 3. Prevention of Penicillin Polymerization.- II. Cephalosporin Polymers.- D. Reactions Between Penicillins and Pharmaceutical Adjuvants.- E. Chemically Reactive Impurities and Degradation Products.- I. Acetylsalicylic Acid.- II. Phenindione.- III. Phenylbutazone.- IV. Corticosteroids.- V. Penicillins.- References.- 3 Immunopathological Mechanisms and Clinical Aspects of Allergic Reactions to Drugs.- With 4 Figures.- A. Introduction.- B. Chemical Properties Involved in the Allergenic Potential of Drugs.- I. Formation of Immunogenic Conjugates.- II. Reactive Derivatives and Metabolites.- III. Requirements for Allergens Eliciting Antibody-Mediated Reactions.- IV. Requirements for Allergens Eliciting Cell-Mediated (Delayed-Type) Allergic Reactions.- V. Impurities and Galenic Factors Involved in Sensitization.- C. Induction of Immune Responses to Drugs: Main Factors Involved.- I. Factors Involving the Sensitizing Drug.- 1. Chemical Structure and Reactivity.- 2. Cross-Sensitization.- 3. Dose, Duration, and Number of Courses of Therapy.- 4. Mode of Administration.- II. Factors Involving the Patient.- 1. The Immune System and the Regulation of Immune Responses to Drugs.- 2. Age and Sex.- 3. Genetic Factors.- 4. Underlying Diseases.- 5. Variable Relationship Between the Immune Response to a Drug and the Incidence of Clinical Allergic Symptoms.- D. Immunopathological Mechanisms of Allergic Reactions to Drugs.- I. Antibody-Mediated Reactions.- 1. Anaphylactic Reactions.- 2. Cytotoxic Reactions.- 3. Immune Complex Reactions.- II. Cell-Mediated (Delayed-Type) Reactions.- III. Reactions by Photosensitivity.- IV. Pseudoallergic Reactions.- 1. Mast Cell and Basophil Degranulation by Complement Components (Anaphylatoxins).- 2. Liberation of Histamine Through Nonimmunologic Mechanisms.- 3. Pseudoallergic Reactions to Drugs Interfering with Prostaglandin Synthesis.- E. Clinical Forms of Allergic Reactions to Drugs.- I. Anaphylactic Shock.- II. Serum Sickness.- III. Fever.- IV. Hematologic Reactions.- 1. Hemolytic Anemia.- 2. Agranulocytosis.- 3. Thrombocytopenia.- 4. Eosinophilia.- V. Hepatic Disorders.- VI. Renal Diseases.- VII. Reactions Affecting the Respiratory Tract.- 1. Asthma.- 2. Infiltrative and Fibrotic Pulmonary Reactions.- VIII. Drug-Induced Autoimmunity.- IX. Vasculitis.- X. Digestive Tract and Other Manifestations.- XI. Skin Manifestations.- References.- 4 Cutaneous Manifestations of Drug Allergy.- A. Pathogenesis and Classification.- I. Anaphylaxis, Urticaria, Angioedema.- II. Late Urticarial Reactions.- III. Serum Sickness.- IV. Maculopapular Rashes.- V. Erythema Multiforme and Stevens-Johnson Syndrome.- VI. Allergic Vasculitis.- VII. Erythema Nodosum.- VIII. Purpura.- IX. Purpura Pigmentosa Progressiva.- X. Fixed Eruptions.- XI. Lyell’s Syndrome (Toxic Epidermal Necrolysis).- XII. Drug-Induced Lupus Erythematosus.- XIII. Allergic and Photoallergic Contact Dermatitis.- B. Diagnosis of Allergic Drug Reactions Involving the Skin.- References.- 5 Allergy of the Respiratory Tract to Low Molecular Weight Chemical Agents.- A. Introduction.- B. Inorganic Chemicals.- I. Halide Complex Salts of Platinum.- 1. Allergy to Complex Platinum Salts.- 2. Immunochemical Analysis of Allergenicity of Platinum Salts.- 3. Inhalation Tests with Platinum Salts.- 4. Serological Findings.- II. Nickel Sulphate.- III. Allergy to Potassium and Sodium Persulphate.- C. Chemical Organic Dusts.- I. Amprolium Hydrochloride.- II. Chloramine-T.- III. Piperazine Hydrochloride.- IV. Antibiotic Dusts: Ampicillin, Benzylpenicillin, 6-Aminopenicillanic Acid and Related Substances.- V. Salbutamol.- VI. Azo and Anthraquinone Dyes.- D. Organic Chemical Fumes and Vapours.- I. Aminoethylethanolamine.- II. Diisocyanates.- 1. Reactions to Diisocyanates Other than TDI.- 2. Modes of Action of TDI.- 3. Antibodies to Other Diisocyanates.- III. Epoxy Resin System Activating Agents.- 1. Phthalic Anhydride-Specific IgE Antibodies.- 2. Trimellitic Acid-Specific IgE and IgG Antibodies.- IV. Miscellaneous Agents.- E. General Comments.- References.- 6 Epidemiology of Drug Allergy: Drug Monitoring.- With 3 Figures.- A. Introduction.- B. Methods of Epidemiology and Drug Monitoring.- I. Comprehensive Inpatient (Intensive) Drug Monitoring.- 1. Euler-Venn Diagram.- 2. Weighted Attributions.- II. Outpatient Drug Monitoring.- III. Spontaneous Reporting of Adverse Reactions to Drugs.- IV. Use of Record Linkage for Drug Surveillance.- C. The Patient.- I. Disposition.- 1. Allergy to Small Molecular Drugs.- 2. Atopy and Adverse Drug Reactions: Drug Allergies.- 3. Idiosyncrasy.- 4. Intolerance.- II. Basic Diseases.- D. Criteria Important to Epidemiology and Drug Monitoring.- I. The Patient and the Adverse Reaction.- 1. Characteristics of Clinical and Laboratory Adverse Reactions: Distinction from Non-Drug Reactions.- 2. Definition of Clinical Syndromes and Laboratory Findings.- 3. Time Factors in Adverse Drug Reactions.- 4. Frequency of Adverse Drug Reactions.- 5. Degree of Importance of Adverse Drug Reactions.- 6. Outcome and Duration of Adverse Drug Reactions.- II. The Drug and Drug Groups.- 1. Different Kinds of Drugs.- 2. Method of Administration of Drug and Drug Allergic Reactions.- E. Practical Consequences.- F. Summary.- References.- 7 Diagnostic Procedures in Drug Allergy.- A. Introduction.- B. Clinical Diagnosis.- C. Immunologic Diagnosis.- D. Skin Testing.- I. Phenylbutazone — BSA Conjugates.- II. Penicillins.- III. Patch Testing.- E. Laboratory Procedures for Investigating Type I Allergic Drug Reactions.- I. Dosage of Serum IgE.- II. Radioallergosorbent Test (RAST).- III. Basophil Degranulation Test.- IV. Histamine Release from Sensitized Leukocytes.- F. In Vitro Investigation of Type II Reactions.- I. Drug-Induced Allergic Hemolysis.- II. Drug-Induced Thrombocytopenia.- 1. Inhibition of Clot Retraction.- 2. Drug-Dependent Platelet Agglutination.- 3. Complement Fixation Test for Drug-Induced Thrombocytopenia.- III. Drug-Induced Agranulocytosis.- 1. Serologic Methods.- 2. Lymphocyte Stimulation.- G. Laboratory Procedures to Detect Serum-Sickness Syndrome (Type III).- I. Determination of Immune Complexes.- II. Determination of Circulating Antibodies.- H. Laboratory Diagnosis of Type IV Reactions or Delayed Hypersensitivity.- I. Lymphocyte Transformation Test.- II. Leukocyte Migration Inhibition Test.- J. Conclusions.- References.- 8 Prevention and Treatment of Drug Allergies.- A. Evaluation of the Allergenic Potential of Drugs.- B. Preventive Measures in Drug Allergy.- C. Prevention of Allergic Reactions by Accurate Diagnosis of Drug Allergy in the Allergic Patient.- D. Specific Inhibition of Antibody-Mediated Reactions to Drugs.- E. Symptomatic Treatment of Allergic Reactions to Drugs.- F. Hyposensitization and Induction of Long-Lasting Immunological Tolerance to Drugs.- References.- Section II: Allergic Reactions to Specific Drugs.- 9 Major Drugs Acting on the Central Nervous System.- A. General Anesthetics.- I. Halothane.- II. Other General Anesthetics.- III. Intravenous Anesthetic Agents.- B. Sedatives, Hypnotics, and Tranquillizers.- I. Phenothiazines.- II. Barbiturates.- III. Others.- C. Narcotics.- D. Anti-Epileptic Drugs.- E. Ethanol.- F. Anti-Depressive Drugs.- G. Stimulants and Hallucinogens.- H. L-Dopa.- J. Relaxants.- K. Analgesic Agents.- References.- 10 General and Local Anaesthetics.- With 6 Figures.- A. Hypersensitivity Reactions to Intravenous Anaesthetics.- I. Clinical Manifestations.- II. Predisposing Factors.- III. Relative Incidence with Various Agents.- 1. Barbiturates.- 2. Eugenols.- 3. Steroid Anaesthetics.- B. Hypersensitivity Reactions to Volatile General Anaesthetics.- I. Halothane-Associated Liver Damage.- 1. Incidence.- 2. Evidence in Support of an Allergic Mechanism.- 3. Reactions to Other Halogenated Volatile Anaesthetics.- 4. Possible Role of Idiosyncrasy in Hepatitis Associated with Halogenated Volatile Anaesthetics.- C. Allergy to Local Anaesthetics.- I. Structural Basis.- II. Investigation of Reactions to Local Anaesthetics.- 1. Skin Tests.- 2. Other In Vivo Tests.- 3. In Vitro Allergy Tests.- References.- 11 Analgesics and Nonsteroidal Anti-Inflammatory Drugs.- With 2 Figures.- A. Classification and Mode of Action of Analgesics and Nonsteroidal Anti-Inflammatory Drugs.- B. Prevalence of Adverse Drug Reactions.- C. Clinical Manifestations of Adverse Reactions.- I. Systemic Anaphylaxis.- II. Aspirin-Induced Asthma.- 1. Definition.- 2. Prevalence.- 3. Pathogenesis.- 4. Clinical Symptoms and Laboratory Findings.- 5. Diagnosis.- 6. Prevention and Therapy.- III. Asthma Relieved by Aspirin.- IV. Urticaria and Angioedema.- 1. Intolerance to Aspirin.- 2. Hypersensitivity to Pyrazolone Drugs.- V. Other Skin Reactions Produced by Analgesics.- VI. Liver Damage.- VII. Kidney Injury.- VIII. Hypersensitivity in Lupus Erythematosus.- IX. Blood Dyscrasias.- 1. Agranulocytosis and Pancytopenia.- 2. Aspirin-Induced Thrombocytopenia.- X. Peripheral Neuropathies.- References.- 12 Neuromuscular Blocking Drugs.- With 8 Figures.- A. Introduction.- B. In Vivo Diagnostic Procedures.- I. Skin Tests.- II. Response to an Intravenous Test Dose.- C. In Vitro Tests.- I. Histamine Release from Leucocytes.- II. Passive Sensitisation Experiments.- III. Lymphocyte Transformation Test.- IV. Serum IgE Measurements.- D. Mechanism of Reactions to Depolarising Agents (Suxamethonium).- I. Clues from Case Histories and Other Clinical Findings.- II. Immunochemical Considerations on the Nature of the Allergen.- III. Leucocyte Histamine Release by Suxamethonium.- 1. Effect of Serum.- 2. Dose-Response Relationships.- 3. Effect of Acetylcholine on the Response to Suxamethonium.- 4. Effect of Non-Depolarising Blockers on Histamine Release by Suxamethonium.- 5. Effect of Calcium on Histamine Release.- IV. Histamine Release as a Manifestation of Idiosyncrasy.- E. Mechanism of Reactions to Non-Depolarising Agents.- I. General Structural Features Associated with Histamine Release.- II. Relation of Leucocyte Histamine Release to Skin Wheal and Flare Responses and Related Phenomena.- III. Calcium Dependence of Histamine Release.- IV. Effect of Acetylcholine on Histamine Release by Non-Depolarising Agents.- V. Relation Between Allergy and Idiosyncrasy.- References.- 13 Drugs Used Topically.- A. Epidemiology.- B. Clinical Aspects of Contact Allergy.- C. Immunochemical, Pharmaceutical, and Pharmacologic Aspects.- D. Diagnostic Tests.- E. Anti-Psoriasis Agents.- I. Tar.- II. Dithranol.- III. Corticosteroids.- IV. Salicylic Acid.- V. Mechlorethamine.- VI. 6-Aminonicotinamide.- VII. Thioxolone.- VIII. 1,8,9-Triacetoxyanthracene.- IX. Tretinoin.- X. 8-Methoxypsoralen.- F. Local Anesthetics.- I. Benzocaine.- II. The Amide Group of Local Anesthetics.- III. Propanidid.- IV. Proxymetacaine.- V. Falicain.- VI. Benzamine Lactate.- G. Antipruritic Agents.- I. Antihistamines.- II. Phenol and Resorcinol.- III. Menthol.- IV. Crotamiton.- V. Nitrofurylaminothiadazoles.- VI. Oxypolyethoxydodecane.- VII. Dimethisoquin.- VIII. Zirconium Compounds.- IX. Fragrances and Preservatives in Antipruritic Agents.- H. Antiperspirants.- I. Aluminum Salts.- II. Formaldehyde.- III. Glutaraldehyde.- IV. Anticholinergic Agents.- V. Zirconium Salts.- J. Local Antibiotics and Chemotherapeutics.- I. Neomycin.- II. Gentamycin.- III. Penicillin.- IV. Chloramphenicol.- V. Bacitracin.- VI. Polymyxin-B Sulfate.- VII. Tetracyclines.- VIII. Erythromycin.- IX. Sulfonamide.- X. Nitrofurazone.- XI. Clindamycin.- XII. Sodium Fusidate.- XIII. Streptomycin.- XIV. Yirginiamycin.- XV. Xanthocillin.- XVI. Mafenide.- XVII. Sulfur.- XVIII. Halogenated Hydroxyquinolines.- K. Antifungal Agents.- I. Nystatin.- II. Variotin.- III. Undecylenic Acid.- IV. Imidazole Derivatives.- V. Tolnaftate.- VI. Dibenzthione.- VII. Pyrrolnitrin.- VIII. Zinc Pyrithone.- L. Steroids.- I. Corticosteroids.- II. Dianabol Cream.- III. Estrogens.- M. Antiseptics and Disinfectants.- I. Quaternary Ammonium Compounds.- II. Chlorhexidine.- III. Hexachlorophene.- IV. Dichlorophene.- V. Triphenylmethane Dyes.- VI. Acridine Dyes.- VII. Rivanol.- VIII. Fenticlor.- IX. Formaldehyde.- X. Tetramethylthiuram Disulfide.- XI. Hexomedine.- XII. Iodine and Iodides.- XIII. Alcohols.- XIV. Triclosan.- XV. Triclocarban.- XVI. TEGO.- XVII. Glutaraldehyde.- XVIII. Mercurials.- XIX. Silver Nitrate.- N. Preservatives.- I. Parabens.- II. Propylene Glycol.- III. Sorbic Acid.- IV. Chlorocresol and p-Chloro-m-xylenol.- V. Chloracetamide.- VI. Nordihydroguaiaretic Acid.- VII. BHA and BHT.- VIII. Propyl Gallate.- IX. Imidazolidinyl Urea.- X. Other Preservatives.- O. Vitamins.- I. Tretinoin.- II. Thiamine.- III. ?-Tocopherol.- IV. Other Vitamins.- P. Photocontact Dermatitis.- I. Halogenated Salicylanilides.- II. Chloro-2-phenylphenol.- III. Bithionol.- IV. Hexachlorophene.- V. Fenticlor.- VI. Multifungin.- VII. Jadit.- VIII. Chlorhexidine.- IX. Esters of p-Aminobenzoic Acid.- X. Sulfonamides and Phenothiazines.- XI. Digalloyl Trioleate.- XII. Captan.- XIII. Coal Tar.- XIV. 8-Methoxypsoralen.- XV. 6-Methylcoumarin.- XVI. Hydrocortisone.- Q. Vehicle Constitutents.- I. Petrolatum.- II. Lanolin.- III. Emulsifiers.- IV. Aliphatic Alcohols.- V. Polyethylene Glycol.- VI. Glycerol.- VII. Propylene Glycol.- VIII. Ethylenediamine Hydrochloride.- IX. Ethylsebacate.- X. Freons.- R. Perfumes.- S. Plant-Derived Topical Drugs.- I. 8-Methoxypsoralen.- II. Arnica Tincture.- III. Camomile.- IV. Coumarin.- V. Tincture of Benzoin.- VI. Podophylin.- VII. Rosin (Colophony).- VIII. Gums.- IX. Vegetable Turpentine.- X. Wood and Coal Tar.- XI. Propolis.- T. Miscellaneous Agents.- I. 5-Fluorouracil.- II. Tromantidine Hydrochloride.- III. Idoxuridine.- IV. Neutral Red.- V. Suntan Preparations.- VI. Dihydroxyacetone.- VII. Hydroquinone and Derivatives.- VIII. Resorcinol.- IX. Benzoyl Peroxide.- X. Epinephrine and Derivatives.- XI. Pyrazolone Compounds.- XII. Bufexamac.- XIII. Nitroglycerin.- XIV. Allylthiocarbamide.- XV. Heparinoid.- XVI. TEA-Coco Hydrolyzed Protein.- XVII. Metoprolol.- U. Conclusions.- References.- 14 Antihistamines.- A. Introduction.- B. The Nature and Classification of the Antihistamines.- C. The Role of Tartrazine in Allergic Antihistamine Reactions.- D. The Nitrogen-Linked Ethylenediamines.- I. The Asthmatic Patient and Ethylenediamine Sensitivity.- II. Industrial Dermatitis due to Ethylenediamine Sensitivity.- 1. Epoxy Resin Dermatitis.- 2. Machine Worker’s Dermatitis.- III. The Relationship of the Hydroxyzines to Ethylenediamine.- IV. The Relationship of the Piperazine (Cyclizine) Antihistamines to Ethylenediamine.- E. The Oxygen-Linked Ethanolamine Antihistamines.- I. Systemic “Endogenic” Contact Dermatitis to Ethanolamines.- II. Photoallergic Dermatitis due to Diphenhydramine.- F. The Phenothiazines.- I. Promethazine Hydrochloride.- II. Cross-Reactions Between the Phenothiazine Antihistamines and Other Phenothiazine Compounds.- III. Exposure of Medical and Nursing Personnel to Phenothiazines.- IV. Exposure of Veterinarians and Farmers to Phenothiazines.- V. Exposure to Methylene Blue.- VI. Varieties of Allergic Reactions to Phenothiazine Compounds.- G. The Carbon-Linked Alkylamine (Propylamine) Antihistamines.- H. Miscellaneous Antihistamines.- J. Facial Dyskinesia from the Antihistamines.- References.- 15 Drugs Acting on the Cardiovascular System.- With 9 Figures.- A. Incidence of Hypersensitivity Reactions.- I. Cardiac Glycosides.- II. Quinidine.- III. Procainamide.- IV. Adrenergic Neuron Blocking Agents.- V. Hydralazine.- VI. Beta-Adrenoceptor Blocking Drugs.- B. Clinical Aspects of the Adverse Effects.- I. Drug-Induced Lupus Erythematosus.- II. Thrombocytopenia.- III. Hemolytic Anemia.- IV. Cutaneous Manifestations.- V. Specific Organ Damage Induced by Cardiovascular Drugs.- 1. Liver.- 2. Heart.- VI. Oculomucocutaneous Syndrome.- 1. Cutaneous Manifestations.- 2. Eye Lesions.- 3. Sclerosing Peritonitis.- 4. Oral/Nasal Lesions.- 5. Hearing Impairment.- 6. Fibrotic Reactions.- VII. Oculomucocutaneous Syndrome and ?-Blocking Drugs Other than Practolol.- 1. Propranolol.- 2. Alprenolol.- 3. Timolol.- C. Immunopharmacological Aspects.- I. Cardiac Glycosides.- 1. Digitoxin.- 2. Digoxin.- 3. Gitaloxin.- 4. Gitoxin.- 5. Lanatoside C.- 6 Ouabain.- 7. Proscillaridin.- II. Quinidine.- III. Procainamide.- IV. Hydralazine.- V. Beta-Adrenoceptor Blocking Drugs.- VI. Methyldopa.- D. Clinical Immunological Aspects.- I. Drug-Induced Lupus Erythematosus.- II. Thrombocytopenia.- III. Oculomucocutaneous Syndrome.- IV. Mechanism of Practolol-Induced Tissue Damage.- V. Hemolytic Anemia.- 1. Stibophen.- 2. Penicillin.- 3. Methyldopa.- E. Conclusion.- References.- 16 Penicillins and Cephalosporins.- With 10 Figures.- A. Introduction.- B. Penicillins.- I. The Formation of Antigenic Determinants from Penicillins.- 1. The Penicilloyl Determinant.- 2. The Penicillenate Determinant.- 3. Penicilloic Acid.- 4. The Penicillanyl Determinant.- 5. The Penamaldate and Penaldate Determinants.- 6. The D-Penicillamine Determinant.- 7. The Penicoyl Derivatives.- 8. Penicillin Polymers.- 9. Protein Impurities.- 10. Role of the Side Chain in Penicillin Allergy.- II. Clinical Aspects.- 1. Anaphylactic and Anaphylactoid Reactions.- 2. Urticaria.- 3. Serum-Like Disease.- 4. Morbilliform Exanthema.- 5. Hematologic Disorders.- 6. Kidney and Vascular Disorders.- 7. Other Manifestations.- III. Epidemiology and Frequency of Allergic Reactions.- IV. Diagnostic Tests.- 1. Skin Tests.- 2. Antibody Detection Techniques.- 3. Cellular Tests.- C. Cephalosporins.- I. Immunologic Aspects of Hypersensitivity to Cephalosporins.- 1. Immunogenicity of the Cephalosporins.- 2. Formation of Antigenic Determinants.- 3. Role of the Side Chain in Immunological Reactivity.- 4. Protein Impurities and Polymers.- II. Clinical Aspects.- III. Epidemiology and Frequency of Allergic Reactions.- IV. Diagnostic Tests.- D. Conclusions.- References.- 17 Other Antibiotics.- With 8 Figures.- A. Introduction.- B. Tetracyclines.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Tetracycline-Specific Antibodies.- 3. Tetracycline-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- C. Chloramphenicol and Thiamphenicol.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Chloramphenicol-Specific Antibodies.- 3. Chloramphenicol-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- D. Aminoglycosides.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- 1. Streptomycin and Dihydrostreptomycin.- 2. Deoxystreptamine Aminoglycosides.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Aminoglycoside-Specifie Antibodies.- 3. Aminoglycoside-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- E. Polymyxins.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Polymyxin-Specific Antibodies.- 3. Polymyxin-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- F. Rifamycins.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Rifamycin-Specific Antibodies.- 3. Rifamycin-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- G. Macrolides.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Macrolide-Specific Antibodies.- 3. Macrolide-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- H. Lincomycins.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Lincomycin-Specific Antibodies.- 3. Lincomycin-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- J. Miscellaneous Antibiotics.- I. Vancomycin.- II. Spectinomycin.- III. Novobiocin.- References.- 18 Other Antibacterial Drugs.- A. Introduction.- B. Sulfonamides Including Benzylpyrimidine Sulfonamides.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Sulfonamide-Specific Antibodies.- 3. Sulfonamide-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- C. Nitrofurantoin.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Nitrofurantoin-Specific Antibodies.- 3. Nitrofurantoin-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- D. Nalidixic, Pipemidic, and Oxolonic Acids.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Nalidixic, Pipemidic, and Oxolonic Acid-Specific Antibodies.- 3. Nalidixic, Pipemidic, and Oxolonic Acid-Specific Lymphocyte Reactions.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- E. Isoniazid.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Isoniazid-Specific Antibodies.- 3. Isoniazid-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- F. Ethambutol.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Ethambutol-Specific Antibodies.- 3. Ethambutol-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- G. Sulfones.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Sulfone-Specific Antibodies.- 3. Sulfone-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- H. Clofazimine.- I. Physicochemical and Pharmacologic Properties.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Clofazimine-Specific Antibodies.- 3. Clofazimine-Specific Lymphocyte Reactivity.- V. Experimental Studies in Animals.- VI. Conclusions Concerning Possible Pathomechanisms.- References.- 19 Antifungal, Anthelmintic, and Antiprotozoal Drugs.- With 9 Figures.- A. Introduction.- B. Antifungal Drugs.- I. Systemic Agents.- II. Topical Agents.- C. Anthelmintic Drugs.- I. Piperazines.- II. Benzimidazole and Imidazothiazoles.- III. Diethylcarbamazine.- D. Antiprotozoal Drugs.- I. Introduction.- II. Quinine.- III. Other Antimalarial Drugs.- References.- 20 Solutions and Emulsions Used for Intravenous Infusions.- With 7 Figures.- A. Introduction.- B. Plasma Substitutes.- I. Historical.- II. General Physicochemical Properties.- III. General Clinical Aspects.- IV. Incidence.- C. Plasma Protein Fractions.- I. Physicochemical and Pharmaceutical Aspects.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Specific Antibodies.- 3. Lymphocyte Transformation Test.- V. Potential Pathomechanisms.- D. Dextran.- I. Physicochemical and Pharmaceutical Aspects.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Specific Antibodies.- 3. Lymphocyte Transformation Test.- V. Potential Pathomechanisms.- VI. Miscellaneous.- E. Gelatin Derivatives.- I. Physicochemical and Pharmaceutical Aspects.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Specific Antibodies.- 3. Lymphocyte Transformation Test.- V. Potential Pathomechanisms.- VI. Miscellaneous.- F. Hydroxyethylstarch.- I. Physicochemical and Pharmaceutical Aspects.- II. Immunochemistry and Immunology.- III. Clinical Aspects.- IV. Results of Diagnostic Tests.- 1. Skin Tests.- 2. Specific Antibodies.- 3. Lymphocyte Transformation Test.- V. Potential Pathomechanisms.- VI. Miscellaneous.- G. Polyvinylpyrrolidone.- I. Physicochemical and Pharmaceutical Aspects.- II. Immunochemistry and Immunology.- III. Miscellaneous.- H. Parenteral Nutrition.- I. General Aspects.- II. Sugars.- 1. Glucose.- 2. Galactose.- 3. Invertose.- 4. Mannitol.- III. Amino Acids.- 1. Physicochemical and Pharmaceutical Aspects.- 2. Adverse Reactions, Including Potential Pathomechanisms.- IV. Fat Emulsions.- 1. Physicochemical and Pharmaceutical Aspects.- 2. Immunochemistry and Immunology.- 3. Clinical Aspects.- 4. Incidence.- 5. Results of Diagnostic Tests.- 6. Potential Pathomechanisms.- References.- 21 Gastrointestinal Drugs.- A. Introduction.- B. Antacids.- C. Gastric Antisecretory Drugs.- D. Laxatives.- E. Antidiarrheal Agents.- F. Anti-Inflammatory Drugs.- G. Miscellaneous Drugs.- References.- 22 Intolerance to Food and Drug Additives.- With 1 Figure.- A. Introduction.- B. Symptoms of Intolerance.- I. Hyperkinetic Behavior Disturbance.- II. Contact Dermatitis.- 1. Dyes.- 2. Antioxidants.- 3. Preservatives.- 4. Flavors.- 5. Stabilizers.- III. Recurrent Urticaria and Angioedema.- IV. Asthma, Rhinorrhea, and Nasal Polyps.- V. Purpura.- VI. Other Symptoms of Intolerance.- C. Mechanisms.- D. Diagnosis of Intolerance.- E. Food and Drug Labeling.- References.- 23 Vitamins.- A. Introduction.- I. The Drug-Equivalent Use of Vitamins.- II. Allergic Reactions to Vitamins.- B. Vitamin A.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin A.- C. Vitamin B1.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin B1.- D. Vitamin B2.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin B2.- E. Vitamin B6.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin B6.- F. Vitamin B12.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin B12.- G. Vitamin C.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin C.- H. Biotin.- J. Folic Acid.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Folic Acid.- K. Nicotinic Acid and Nicotinamide.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Nicotinic Acid and Nicotinamide.- L. Pantothenic Acid.- M. Vitamin D.- N. Vitamin E.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin E.- O. Vitamin K.- I. Physicochemical and Pharmacologic Aspects.- II. Allergic Reactions to Vitamin K.- P. Conclusions.- References.- 24 Corticotrophins and Corticosteroids.- With 6 Figures.- A. Frequency of Accidents due to Corticotrophins.- B. Clinical Aspects of Allergic Reactions to ACTH.- C. Etiology and Physiopathology of Accidents.- D. Diagnosis of Allergy to ACTH.- E. Therapy.- F. Allergy to Corticosteroids.- I. Neurologic Symptoms.- II. Contact Dermatitis.- III. Anaphylactoid Reactions.- References.- 25 Hypersensitivity Reactions to Hormones.- A. Protein and Polypeptide Hormones.- I. Immunochemical and Pharmacological Aspects.- II. Clinical Aspects.- III. Results of Diagnostic Tests.- B. Prostaglandins.- I. Immunochemical and Pharmacological Aspects.- II. Clinical Aspects.- III. Results of Diagnostic Tests.- C. Adrenocorticosteroids.- I. Immunochemical and Pharmacological Aspects.- II. Clinical Aspects.- III. Results of Diagnostic Tests.- 1. Cutaneous Tests.- 2. Direct Challenge.- D. Sex Steroids and Oral Contraceptive Drugs.- I. Immunochemical and Pharmacological Aspects.- II. Clinical Aspects.- III. Results of Diagnostic Tests.- E. Conclusion.- References.- 26 Allergy to Insulin.- A. Epidemiology and Frequency of Allergic Reactions.- B. Clinical Aspects.- C. Immunological, Pharmaceutical, and Pharmacological Aspects.- D. Results of Diagnostic Tests.- E. Special Considerations.- References.- 27 Radiologic Contrast Media.- A. Introduction.- B. Chemical Structures of Contrast Media.- C. Clinical Manifestations.- D. Pathogenic Mechanisms.- I. Hypersensitivity Mechanisms.- II. Direct Histamine Release.- III. Activation of Complement Factors.- IV. Inhibition of Acetylcholine Esterase.- E. Diagnostic Tests.- I. Skin Tests.- II. Lymphocyte Transformation Test.- III. Provocation Tests.- F. Prevention.- I. Risk Factors.- II. Premedication.- References.