عنوان

Pharmacology of the Skin II :

3642740545

9783642740541

b537900

Pharmacology of the Skin II :

[Book]

Methods, Absorption, Metabolism and Toxicity, Drugs and Diseases

edited by Malcolm W. Greaves, Sam Shuster.

Berlin, Heidelberg

Springer Berlin Heidelberg

1989

(xxxvii, 587 pages 55 illustrations)

Handbook of experimental pharmacology, 87 / 2.

Acute Effect of PUVA on Normal Skin.- IV. Clinical Uses of PUVA.- 1. Vitiligo.- 2. Psoriasis.- 3. Mycosis Fungoides.- 4. Urticaria Pigmentosa.- 5. Light-related Dermatoses.- 6. Eczema.- 7. Other Disorders.- V. Treatment Principles.- 1. Dosimetry.- 2. Immunological Effects.- 3. Other Skin Changes.- 4. Skin Cancer.- 5. Skin Ageing.- 6. Miscellaneous Cutaneous Toxicities Associated with PUVA Therapy.- 7. Ophthalmological Risks.- 8. Systemic Toxicity of PUVA.- References.- 39 Dapsone and Sulphapyridine.- A. Introduction.- B. Chemical Aspects.- I. Structures of DDS, SP and Their Circulating Metabolites.- II. Assay Methods.- C. Pharmacokinetics and Metabolism in Humans.- D. Therapeutic Effects in Dermatoses.- E. Therapeutic Effects in Rheumatoid Arthritis.- F. Anti-inflammatory Actions in Animals.- G. Comparative Pharmacokinetics and Metabolism.- H. In vitro Actions and Possible Mechanisms of Action.- J. Concluding Remarks.- References.- 40 Zinc Deficiency.- A. Introduction.- B. Zinc Deficiency.- I. Acrodermatitis Enteropathica.- II. Prematurity and Bottle Feeding.- III. Availability of Zinc in the Diet.- IV. Intravenous Feeding.- V. Malabsorption and Inflammatory Bowel Disease.- VI. Treatment with Chelating Agents and Diuretics.- VII. Burns and Skin Diseases.- VIII. Dialysis.- IX. Alcoholism and Cirrhosis.- C. Zinc and Wound Healing.- D. Zinc and Acne Vulgaris.- E. Zinc and Herpes Simplex.- F. Possible Mechanisms of the Manifestations of Zinc Deficiency.- I. Immunological Responsiveness.- II. Essential Fatty Acid Metabolism.- III. Cell Membrane Stability.- IV. Vitamin A Metabolism.- V. Buccal Epithelial Proliferation.- VI. Collagen.- References.- 41 The Ichthyoses.- A. Introduction.- B. Treatment of the Ichthyoses.- I. Treatment Directed Towards an Underlying Cause.- II. Symptomatic Treatments.- 1. General Management.- 2. Retinoids.- 3. Topical Therapies.- a) Emollients.- b) Osmotic Agents.- c) Keratolytic (Desquamatory) Agents.- d) Essential Fatty Acids.- References.- 42 Tropical Skin Diseases.- A. Introduction.- B. Onchocerciasis (River Blindness).- C. Cutaneous Leishmaniasis.- D. Leprosy.- E. Yaws.- References.

Influence of Monoaromatic and Polyaromatic Retinoids on Neonatal Mouse Keratinocyte Cell Differentiation and Proliferation In Vitro.- References.- 26 Hypolipidaemic Agents in the Treatment of Xanthomata.- A. Introduction.- B. Treatment of Hyperlipidaemia.- I. Cholestyramine.- II. Colestipol.- III. Nicotinic Acid.- IV. Clofibrate.- V. Probucol.- VI. Drug Combinations.- References.- 27 Drugs Acting on Dermal Connective Tissue.- A. Introduction.- B. Drugs Acting at the Level of Transcription and Translation.- I. Glucocorticoids.- II. Sex Hormones.- III. Photochemotherapy.- IV. Antimitotics and Antibiotics.- V. Growth Factors.- 1. Epidermal Growth Factor.- 2. Fibroblast Growth Factors.- 3. Platelet-Derived Growth Factor.- 4. Insulin and Insulin-Like Growth Factors.- 5. Cytokines.- 6. Tumour Angiogenesis Factor and Angiogenesis Inhibitors.- 7. Transforming Growth Factors.- VI. Oncogenes.- VII. Precursor Sequences of Procollagens.- C. Drugs Acting on Hydroxylation.- I. Amino Acid Analogues.- II. Iron Chelators.- III. Vitamin C.- D. Drugs Acting on Secretion.- I. Cytoskeleton-Disruptive Drugs.- II. Canavanin.- III. Tunicamycin.- IV. Ionophores.- E. Drugs Acting on Cross-Linking.- I. Lathyrogens.- II. Penicillamine.- III. Copper.- IV. Sex Hormones.- V. Flavonoids.- VI. Catechol Analogues.- VII. Radiotherapy.- VIII. Coagulation Factor XIIIa.- F. Drugs Acting on Degradation.- I. Diphenylhydantoin.- II. Prostaglandins.- III. Vitamin A and Retinoids.- IV. Enzyme Replacement Therapy.- V. Elastase Inhibitor.- G. Conclusions.- References.- 28 Fungal Skin Infections.- A. Introduction.- B. Management of Fungal Skin Infections.- I. Dyes and Keratolytic Agents.- II. Specific Anti-fungal Agents.- III. Polyene Anti-fungal Agents.- IV. Imidazole Anti-fungal Agents.- V. Oral Anti-fungal Drugs Used in Superficial Infections.- 1. Ketoconazole.- 2. Griseofulvin.- 3. Other Oral Anti-fungal Drugs.- C. Conclusion.- References.- 29 Bacterial Infections.- A. Introduction.- B. Normal Skin Flora.- C. Skin Surface Defences.- D. Skin Flora in Disease States.- E. General Principles of Treatment.- I. Non-specific Measures.- II. Topical.- III. Systemic.- F. Antibiotics.- I. Penicillins.- II. Macrolides.- III. Polymyxins.- IV. Aminoglycosides.- V. Cephalosporins.- VI. Tetracyclines.- VII. Anti-tuberculous Drugs.- VIII. Metronidazole.- G. Clinical Situations.- I. Infections.- 1. Impetigo.- 2. Furunculosis.- 3. Ecthyma.- 4. Cellulitis.- 5. "Gram-negative" Infections.- 6. Erythrasma.- 7. Tuberculosis.- 8. Miscellaneous.- II. Diseases Exacerbated by Bacteria.- 1. Atopic Dermatitis.- 2. Psoriasis.- 3. Napkin Dermatitis.- 4. Leg Ulcers.- 5. Hidradenitis Suppurativa.- 6. Miscellaneous.- III. Infection in Immune-Compromised Patients.- References.- 30 Herpes Virus Infections.- A. Introduction.- B. Classification.- C. Herpes Simplex.- I. Latency and Recurrence.- D. Varicella Zoster.- E. Therapy.- I. Idoxuridine.- II. Adenine Arabinoside.- III. Trifluorothymidine.- IV. Acyclovir.- 1. Herpes Simplex Infection.- 2. Herpes Zoster Infection.- V. Bromovinyldeoxyuridine.- VI. Interferon.- F. Drug Resistance.- G. Conclusion.- References.- 31 The Urticarias.- A. Introduction.- B. Histamine.- I. Mast Cell Release.- II. Mast Cell Numbers and Stability.- III. Basophil Responses.- IV. Reactivity of Blood Vessels.- V. Involvement of Other Mediators.- C. Mediators Derived from Arachidonic Acid.- I. Arachidonate Cyclo-oxygenase Products.- II. Arachidonate Lipoxygenase Products.- D. Neutrophil and Eosinophil Chemo tactic Factors.- E. Platelet-Activating Factor.- F. Platelet Factor.- G. Eosinophil Granule Proteins.- H. Proteases.- J. Neuropeptides.- K. Acetylcholine.- L. Mediators Derived from Plasma.- I. Kinins.- M. Hereditary Angio-oedema (HAE).- I. Acquired C1 Inhibitor Deficiency.- N. Fibrin and Fibrinolysis.- O. Complement.- P. Cellular Infiltration.- References.- 32 Eczema.- A. Introduction.- B. Treatment Directed at Causative Mechanisms.- I. Asteatotic Eczema.- II. Atopic Eczema.- III. Contact Eczema.- IV. Infected Eczema.- V. Seborrhoeic Eczema.- VI. Stasis Eczema.- C. Symptomatic Treatment.- I. Corticosteroids.- II. Tar Applications.- III. Emollients.- IV. Antihistamines.- V. Cyclosporin A.- VI. Cytostatic Drugs.- VII. Photochemotherapy.- VIII. Grenz Ray Therapy.- D. Specific Eczematous Dermatoses.- I. Lichenified Eczema.- II. Nodular Prurigo.- III. Erythroderma and Exfoliative Dermatitis.- IV. Atopic Eczema.- References.- 33 Treatment of Psoriasis.- A. Introduction and Aetiological Factors.- I. Genetics.- II. Precipitating Factors.- 1. Streptococcal Infection.- 2. Koebner Phenomenon.- 3. Stress.- 4. Lithium.- III. Abnormalities in Skin and Other Organs.- 1. Increased Epidermal Proliferation.- 2. Leukotriene Production.- 3. Immunological Abnormalities.- B. Choice of Treatment.- C. Clearance of Chronic Plaque Psoriasis.- I. Topical Preparations.- 1. Corticosteroids.- 2. Tar.- 3. Dithranol.- II Photochemotherapy (PUVA).- 1. Psoralen Baths.- III. How to Choose Between Tar, Dithranol and PUVA.- D. Prevention of Recurrence of Chronic Plaque Psoriasis.- E. Psoriasis at Special Sites.- I. Face.- II. Scalp.- III. Flexures.- IV. Palms and Soles.- V. Nails.- F. Systemic Treatments (Excluding PUVA).- I. Corticosteroids.- II. Anti-mitotics.- 1. Methotrexate.- 2. Hydroxyurea.- III. Aromatic Retinoids.- IV. Cyclosporin A.- V. Other Treatments.- References.- 34 Anthralin.- A. Introduction.- B. Chemistry.- I. Anthrone-Anthranol Tautomerism.- II. Chemical Assay.- C. Structure-Activity: New Derivatives.- D. Mode of Action.- E. Pharmacokinetics and Metabolism.- I. In Vitro and In Vivo Studies: Human Skin.- II. Animal Studies.- F. Pharmacology of Anthralin Irritation.- I. Quantification of the Erythematous Response.- II. Mediator Studies: Indirect Methods.- III. Mediator Studies: Direct Methods.- G. Therapy.- I. Ingram and Related Regimens.- II. Short-Contact Therapy with Anthralin.- H. Adverse Reactions.- References.- 35 The Treatment of Acne.- A. Introduction.- B. Sebostatic Drugs.- I. Endocrine Inhibitors.- 1. Anti-androgens.- 2. Oestrogens and Oral Contraceptives.- 3. Corticosteroids.- II. Inhibitors of Sebaceous Lipogenesis.- III. Direct Action on Sebaceous Cell: Isotretinoin.- C. Anti-microbials.- I. Tetracycline.- II. Erythromycin.- III. Co-trimoxazole.- IV. Clindamycin.- V. Systemic versus Topical Antibiotics.- VI. Benzoyl Peroxide.- VII. Other Anti-microbials.- D. Miscellaneous Treatments.- I. Tretinoin (Retinoic Acid).- II. Ultraviolet Radiation.- III. Superficial X-ray Therapy.- E. Conclusion.- References.- 36 Pharmacology of Anti-androgens in the Skin.- A. Introduction.- B. Mechanism of Action of Androgens.- C. Anti-androgens: Mode of Action and Chemistry.- I. Inhibitors of 5?-Reductase.- II. Cytosol Receptor Blockers.- III. Spironolactone.- D. Animal Models: Anti-androgens and Sebaceous Gland Function.- E. Clinical Evaluation of Anti-androgens.- F. Topical Anti-androgens.- References.- 37 The Effect of Drugs on Hair.- A. Introduction.- B. The Hair Growth Cycle.- I. Catagen.- II. Telogen.- III. Anagen.- C. Physiological Changes in the Hair Cycle.- D. Assessment of Drug Effects on Hair.- E. Hormones and Hair Growth.- F. Hirsutism.- I. Hormonal Therapy for Hirsutism.- 1. Reduction of Circulating Androgen Levels.- 2. Anti-androgens.- G. Male-Pattern Baldness (Androgenetic Alopecia).- I. Treatments for Androgenetic Alopecia.- 1. Anti-androgens.- 2. Non-hormonal Therapy.- H. Pregnancy and the Contraceptive Pill.- J. Treatments for Alopecia Areata and Alopecia Totalis.- K. Drugs Causing Hair Loss or Hair Gain.- I. Drug-induced Hypertrichosis.- II. Drug-induced Hair Loss.- 1. Cytostatic Agents.- 2. Epidermal Growth Factor.- L. Hair Colour and Shape.- References.- 38 Photochemotherapy.- A. Definition and History.- B. Photobiology.- C. Photochemistry and Photobiology in Relation to Photochemotherapy.- D. Photosensitisation.- E. The Psoralens.- I. Pharmacology.- II. Photochemistry.- III.

Section A: Methods.- 1 Methods for the Study of Proliferative Rates in Epidermis.- A. Introduction.- B. Impractical Methods.- I. The Fraction Labelled Mitoses Method.- II. The Continuous Labelling Method.- C. Methods Suitable for Short-term Study.- I. Incorporation of Tritiated Thymidine into DNA.- II. Proliferative Indices.- III. The Measurement of Rate Parameters in Epidermis.- D. Conclusion.- References.- 2 Tissue and Fluids: Sampling Techniques.- A. Tissue Sampling.- I. Surgical.- II. Epidermal Samples.- III. Separation of Epidermis from Dermis In Vitro.- 1. Physical Separation.- 2. Enzymic Techniques.- 3. Miscellaneous Agents.- IV. Stratum Corneum Sampling.- V. Corneocyte Sampling.- B. Sampling of Secretions.- I. Sebum.- II. Eccrine Sweat.- III. Apocrine Sweat.- IV. Tissue Fluid.- References.- 3 Measurement of Sweating and Sweat Gland Function.- A. Introduction.- B. Total Body Sweat Loss.- C. Local and Regional Sweat Responses.- I. Qualitative Methods.- II. Quantitative Methods.- D. Induction of Sweating.- I. The Isolated Sweat Gland.- II. Apocrine Sweating.- E. Localisation of Abnormalities Within the Sweat Gland.- References.- 4 Measurement of Human Sebaceous Gland Function.- A. Introduction.- I. Histological Methods.- II. Functional Methods.- B. Measurement of Sebum Excretion Date.- I. Gravimetric Technique.- 1. Materials.- 2. Collection of Sebum.- 3. Extraction and Weighing Lipid.- C. Photometric Technique.- D. Sebum Production Rate.- E. Factors Affecting the Measurement of Sebum Excretion Rate.- F. Measurement of Surface Lipid Composition.- References.- 5 Methods for Assessing the Effect of Drugs on Hair and Nails.- A. Hair Loss.- B. In Vivo Assessment of Hair Growth.- I. Hair Cycle Status.- II. Cell Kinetics.- III. Linear Growth.- IV. Hirsutism and Scalp Hair Density.- V. Elemental Analysis.- C. In Vitro Methods for Detecting the Effect of Drugs.- D. Nail Growth.- E. Penetration of Topical Agents.- F. Radiation Penetration.- G. Wood's Light.- References.- 6 Measurement of Drug Action in the Skin: Sensation.- A. Introduction.- B. Methods for Studying Cutaneous Sensation.- I. Types of Measurement.- 1. Intensive.- 2. Time-Dependent and Spatial Measures.- II. Stimulation Techniques.- 1. Mechanical Stimulation.- 2. Thermal Stimulation.- 3. Chemical Stimulation.- III. Experimental Design.- 1. Design of Experiments on Cutaneous Sensation in Laboratory Animals.- 2. Design of Experiments on Cutaneous Sensation in Humans.- C. Effects of Drugs on Cutaneous Sensation.- I. Drugs that produce Sensation.- 1. Pain-producing Agents.- 2. Substances Producing Itch and Other Non-painful Sensations.- II. Drugs that Modify Sensation.- 1. Local Anaesthetics.- 2. Opioid Analgesics.- 3. Anti-inflammatory Agents.- 4. Adrenaline, Acetylcholine, Capsaicin, Gonadal Hormones.- 5. Anti-pruritic Agents.- D. Final Comments.- References.- 7 The Measurement of Itch.- A. Introduction.- B. Subjective Methods.- I. Threshold.- II. Degree.- C. Objective Methods.- I. Nocturnal Bed Movement.- II. Limb Meters.- III. Relationship of Itch and Scratch.- IV. Short-term Measurement of Itch as Scratch.- References.- 8 Measurement of Skin Thickness, Wealing, Irritant, Immune and Ultraviolet Inflammatory Response in Skin.- A. Measurement of Skin Thickness.- I. The Harpenden Skin Fold Caliper.- II. X-ray.- III. Ultrasound.- IV. Use of Skin Thickness for Lesion Measurement and Response to Treatment.- V. Corticosteroid Atrophy of Skin.- B. Measurement of Different Types of Inflammation and Their Response to Therapy.- I. Measurement of Ultraviolet Erythema.- 1. Minimal Erythema Dose.- 2. Quantification of Erythema.- a) Visual Grading.- b) Colour Comparison Charts.- c) Red-Coloured Optical Filters.- d) Reflectance Spectrophotometry.- II. Weal Reactions.- 1. Dermographic Wealing.- III. Irritant Inflammation.- 1. Transepidermal Water loss.- IV. Immune Reactions.- 1. The Immediate (Type I) Response.- 2. The Delayed (Type IV) Response.- References.- 9 Measurement of Drug Action in Skin: Dermal Connective Tissue.- A. Introduction: Selection of Procedures and Biological Models.- B. Physical Parameters.- C. Morphology.- D. Cell Kinetics.- E. Quantitative Measurements.- I. Collagen.- II. Elastin.- III. Proteoglycans and Glycoproteins.- F. Qualitative Measurements.- I. Collagen.- II. Elastin.- III. Proteoglycans and Glycoproteins.- G. Estimation of Turnover Rate.- I. Collagen.- II. Elastin.- III. Proteoglycans and Glycoproteins.- H. Measurement of Defined Biochemical Parameters.- I. Messenger RNA.- II. Intracellular Post-translational Enzymes.- III. Extracellular Processing Enzymes.- IV. Degradation, Enzymes and Products.- References.- 10 Microbiological Sampling Techniques.- A. Introduction.- B. Surface Distribution.- C. Swabbing Methods.- D. Washing Methods.- E. Follicular Sampling.- F. Miscellaneous Techniques.- G. Comment.- References.- 11 Clinical Trial Methods.- A. The Beginnings.- B. Clinical Trial Principles Applied to Dermatology.- C. The Subjects.- D. Trial Design.- I. Concurrent Comparisons.- 1. Independent Groups.- 2. Related Groups.- a) Cross-over Plans.- b) Matched Pairs.- c) Repeated Measurements.- d) Factorial Plans.- II. Historical Comparisons.- E. Power and Statistical Analysis.- F. Allocation to Treatment.- G. "Intention to Treat".- H. Blindness.- J. Measurements.- I. Measurement Scales.- II. Types of Measurement.- K. The Protocol.- L. The Reasons for Performing Therapeutic Trials.- M. Applying the Results of Trials in Practice.- References.- Section B: Absorption, Metabolism and Toxicity.- 12 The Properties of Skin as a Diffusion Barrier and Route for Absorption.- A. The Location and Nature of the Percutaneous Absorption Barrier.- B. Methods of Measuring Percutaneous Absorption.- I. In Vivo Techniques.- II. In Vitro Techniques.- C. In Vivo - In Vitro Comparisons.- D. Mathematical Derivation of Absorption Parameters.- E. Species Comparisons: Relevance of Animal Data to Humans.- F. Metabolism.- G. Control and Prediction of Absorption.- References.- 13 Skin as a Mode for Systemic Drug Administration.- A. Introduction.- B. Therapeutic Objectives of Transdermal Delivery.- C. Design of a Rate-Controlled Scopolamine System.- D. Controlled Systemic Absorption of Nitroglycerin.- E. New Advances in Transdermal Drug Delivery.- I. Catapres - TTS.- II. Estraderm.- F. The Future.- References.- 14 Drug Metabolism in the Skin.- A. Introduction.- B. Drug Metabolism in General.- C. Drug-Metabolizing Enzymes in Skin.- I. General Remarks.- II. Drug Oxidation by Cytochrome P-450.- 1. Aliphatic Oxidation.- 2. Aromatic Oxidation.- III. Hydrolysis of Epoxides by Epoxide Hydrolase.- IV. Hydrolysis by Esterases.- V. Conjugation by Glucuronosyl Transferase and Sulfotransferase.- VI. Conjugation by Glutathione-S-transferase.- VII. Inducibility of Drug-Metabolizing Enzymes.- D. Metabolism of Polycyclic Aromatic Hydrocarbons in the Skin as Related to Carcinogenicity.- E. Conclusions.- References.- 15 Skin Cancer (Excluding Melanomas).- A. Human Skin Cancer.- I. History and Causative Factors.- II. Ultraviolet Radiation Carcinogenesis.- III. Ionizing Radiation Carcinogenesis.- IV. Viruses as Causative Agents.- B. Experimental Skin Carcinogenesis by Chemical Agents.- I. Historical Remarks.- II. Initiation.- III. The Induction of Tumor Development in Initiated Skin.- IV. The Mechanism of Skin Tumor Promotion.- V. Mechanistic Aspects of the Conversion Stage of Experimental Carcinogenesis.- VI. Co-carcinogenesis.- VII. The Potential Importance of the Multistage Model for Prevention of Human Cancer.- References.- 16 Toxicology of Cosmetics.- A. Introduction.- B. Safety Data Required.- I. Scientific Requirements.- II. Legal Requirements.- C. Sources of Safety Data.- I. Scientific Literature.- II. Safety Data from Suppliers.- III. History of Safe Use.- IV. Safety Testing.- D. Toxic Effects.- I. Skin Irritation.- II. Eye Irritation.- III. Skin Sensitisation.- IV. Photoirritation.- V. Photoallergy.- VI.

Sensory Effects.- VII. Systemic Toxicity: Single Exposure Effects.- VIII. Systemic Toxicity: Repeated Exposure Effects.- IX. Teratology.- X. Carcinogenicity.- XI. Mutagenicity.- E. Interpretation of Safety Data.- References.- 17 Drug Sensitisation.- A. Introduction.- B. The Trigger.- C. The Gun.- I. Introduction.- II. Type I.- III. Type II.- IV. Type III.- V. Type IV.- D. The Target.- I. Introduction.- II. Type I.- III. Type II.- IV. Type III.- V. Type IV.- E. The Detection of Drugs Responsible for Allergic Reactions.- F. Management.- References.- Section C: Drugs and Diseases.- 18 H1- and H2-Receptor Antagonists.- A. Introduction.- B. Biological Actions of Histamine.- I. Actions of Histamine on Skin.- II. Action of Histamine on Blood Vessels.- III. Histamine Receptors on Skin Blood Vessels.- C. Animal Studies.- D. Human Studies.- I. Local Administration of Histamine.- II. Evidence for Histamine Receptors on Skin Blood Vessels Following Systemic Administration of Histamine.- III. Histamine-Induced Pruritus.- IV. Other Actions of Histamine in Skin.- V. Clinical Results with H1-and H2-Receptor Antagonists in Chronic Urticaria.- E. Newer Histamine Antagonists.- F. Conclusions.- References.- 19 Clinical Pharmacology of Topical Steroids.- A. Introduction.- I. Structure-Activity Relationship.- II. Mode of Application.- III. Skin Factors.- B. Mode of Action.- I. Steroid Receptors.- II. Inhibition of Prostaglandins.- III. Protein and Collagen Synthesis.- IV. Immunosuppressant Effects.- V. Actions of Microsomal Oxidation.- VI. Other Actions.- C. Assays of Glucocorticoid Activity.- D. Metabolism of Corticosteroids in Skin.- E. Toxic Effects of Glucocorticoids.- I. Local Toxicity.- II. Systemic Effects.- F. Treatment Guidelines.- References.- 20 Glucocorticoids and Lipocortin.- A. Discovery of Lipocortin.- I. Introduction.- II. Cloning and Expression of Lipocortin.- III. Distribution of Lipocortins.- B. Properties of Lipocortin.- I. Inhibition of Phospholipase A2.- II. Inhibition of Cellular Eicosanoid Synthesis.- III. Anti-inflammatory and Other Effects of Lipocortin.- IV. Anti-lipocortin Antibodies and Disease.- References.- 21 Cutaneous Vasodilators.- A. Introduction.- B. Neurovascular Control in the Skin.- C. Pharmacology of the Cutaneous Vasculature.- I. Drugs Acting on the Sympathetic Nervous System.- 1. Adrenergic Neurone-Blocking Agents.- a) Guanethidine.- b) Reserpine.- 2. ?-Adrenergic Blocking Agents.- a) Phenoxybenzamine.- b) Tolazoline.- c) Prazosin.- d) Indoramin.- II. Drugs with Direct Vasodilator Activity.- 1. Nicotinic Acid Esters.- a) Pharmacology.- b) Adverse Effects.- c) Therapeutic Use.- 2. Glyceryl Trinitrate (Nitroglycerin).- a) Pharmacology and Mechanism of Action.- b) Adverse Effects.- c) Therapeutic Use.- 3. Calcium Channel Blocking Agents.- a) Pharmacology.- b) Adverse Effects.- c) Therapeutic Use.- 4. Prostaglandin I2 (Prostacyclin).- 5. Synthetic Analogues.- a) Pharmacology.- b) Adverse Effects.- c) Therapeutic Use.- References.- 22 Fibrinolysis and Fibrinolytic Drugs.- A. Fibrinolysis.- I. Plasminogen.- II. Plasmin.- III. Plasminogen Activation.- 1. Tissue-type Plasminogen Activator (t-PA).- 2. Urokinase.- 3. Endothelial Plasminogen Activator.- 4. Plasmatic Pro-activator.- 5. Streptokinase - Activated Plasminogen Activator.- 6. "Activated" Macrophages. Activator.- 7. Plasminogen Activators in Neoplastic Cells.- 8. Erythrokinase.- 9. Plasminogen Activators in Human Granulocytes.- 10. Indirect Plasminogen Activators.- IV. Inhibitors of Fibrinolysis.- V. Plasminogen Activators in Physiologic Conditions.- VI. Plasminogen Activators in Inflammation.- VII. Plasminogen Activators in Neoplastic Conditions.- VIII. Plasminogen Activation in the Skin.- IX. Physiopathology of the Cutaneous Fibrinolytic System.- X. Methods for Evaluation of Plasminogen Activators in the Skin.- 1. Modified Autohistographic Fibrin Plate Assay with Monoclonal Antibodies Against t-PA and u-PA.- 2. Casein Plate Assay.- 3. Casein Substrate Assay.- 4. Synthetic Substrate Assay.- XI. Autohistographic Method for Evaluation of Inhibitors of Fibrinolysis in the Skin.- B. Drugs Affecting Plasminogen Activator Synthesis and Activity.- I. Steroid Hormones.- II. Polypeptide Hormones and cAMP.- III. Epidermal Growth Factor.- IV. Retinoic Acid.- V. Phorbol Esters.- C. Fibrinolytic Drugs Used in Thrombolytic Therapy.- I. Urokinase.- II. Streptokinase.- III. Tissue-type Plasminogen Activator (t-PA).- IV. Stanozolol.- V. Defibrotide.- VI. Glycosaminoglycans.- D. Therapeutic Use of Fibrinolytic Drugs in Dermatologic Diseases.- References.- 23 Non-steroidal Anti-inflammatory Agents and the Skin.- A. Introduction.- B. Aspirin, Indomethacin and Related Cyclo-Oxygenase Inhibitors.- C. Lipoxygenase Inhibitors.- I. Benoxaprofen.- II. Lonapalene.- D. Future Developments.- References.- 24 Immunosuppressive (Cytotoxic) and Immunostimulant Drugs.- A. Introduction.- B. Corticosteroids.- I. Mode of Action.- 1. Leukocyte Distribution.- 2. Humoral Effects.- 3. Cell-mediated Immunity.- II. Administration.- III. Adverse Effects.- IV. Therapeutic Use.- 1. Pemphigus and Pemphigoid.- 2. Dermatomyositis.- 3. Systemic Lupus Erythematosus.- 4. Pyoderma Gangrenosum.- C. Azathioprine.- I. Pharmacokinetics.- II. Therapeutic Use.- 1. Pemphigus and Pemphigoid.- 2. Lupus Erythematosus.- 3. Dermatomyositis and Polymyositis.- 4. Other Dermatological Diseases.- III. Dosage.- IV. Adverse Effects.- V. Precautions.- VI. Drug Interactions.- VII. Mutagenicity and Carcinogenicity.- D. Methotrexate.- I. Mode of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- IV. Adverse Effects.- V. Hepatotoxicity.- VI. Dosage.- VII. Contraindications.- E. Cyclophosphamide.- I. Mechanism of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- 1. Pemphigus and Pemphigoid.- 2. Lupus Erythematosus.- 3. Other Skin Diseases.- IV. Dosage.- V. Adverse Effects.- F. Gold.- I. Mechanism of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- IV. Adverse Effects.- V. Dosage.- VI. Precautions.- G. Dapsone.- I. Mechanism of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- 1. Dermatitis Herpetiformis.- 2. Other Uses.- IV. Adverse Effects.- V. Dosage.- H. Cloroquine.- I. Mechanism of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- IV. Dosage.- V. Adverse Effects.- VI. Precautions.- J. Cyclosporin.- I. Mechanism of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- 1. Graft-Versus-Host-Disease.- 2. Psoriasis.- 3. Dermatitis.- 4. Other Skin Diseases.- IV. Unwanted Effects.- K. Thalidomide.- I. Therapeutic Uses.- II. Adverse Effects.- III. Dosage.- L. Clofazimine.- I. Mechanism of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- IV. Adverse Effects.- V. Dosage.- M. Colchicine.- I. Pharmacokinetics.- II. Therapeutic Uses.- III. Adverse Effects.- IV. Dosage.- V. Precautions.- N. Levamisole.- I. Mode of Action.- II. Pharmacokinetics.- III. Therapeutic Uses.- IV. Adverse Effects.- V. Dosage.- O. Other Cytostatic Drugs Used in Dermatology.- References.- 25 Three Generations of Retinoids: Basic Pharmacologic Data, Mode of Action, and Effect on Keratinocyte Proliferation and Differentiation.- A. General Aspects.- B. Synthesis of Retinoids.- C. Therapeutic Index, Preclinical Evaluation.- D. First-Generation Retinoids.- I. Tretinoin.- 1. Pharmacokinetics.- II. Isotretinoin.- 1. Pharmacokinetics.- E. Second-Generation Retinoids.- I. Etretinate.- 1. Pharmacokinetics.- II. New Monoaromatics.- F. Third-Generation Retinoids: Arotinoids (Polyaromatics).- I. Arotinoids with a Carbon-Containing Polar End Group.- 1. Pharmacokinetics.- II. Arotinoids with a Sulfur-Containing Polar End Group.- III. Arotinoid Ro-15-0778: The Parent Compound.- G. Retinoids, Intracellular Binding Proteins, and Mechanism of Action.- H. Molecular-Biologic Effects of Synthetic Retinoids.- J.

With contributions by numerous experts

With contributions by numerous experts

Human physiology.

Medicine.

Toxicology.

edited by Malcolm W. Greaves, Sam Shuster.

Malcolm W Greaves

Sam Shuster

[Book]

Y