Pharmacology of the Skin II: Methods, Absorption, Metabolism and Toxicity, Drugs and Diseases by D.J. AthertonPharmacology of the Skin II: Methods, Absorption, Metabolism and Toxicity, Drugs and Diseases by D.J. Atherton

Pharmacology of the Skin II: Methods, Absorption, Metabolism and Toxicity, Drugs and Diseases

byD.J. Atherton

Paperback | February 23, 2012

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The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin as in animal models, where they may be more relevant to human physiology and disease. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of aetiology and mechanism. For example, whilst the argument continued un­ resolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis retinoic acid, was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on aetiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as for the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.
Title:Pharmacology of the Skin II: Methods, Absorption, Metabolism and Toxicity, Drugs and DiseasesFormat:PaperbackDimensions:587 pages, 24.2 × 17 × 0.01 inPublished:February 23, 2012Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

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ISBN - 10:3642740561

ISBN - 13:9783642740565

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Table of Contents

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-Oxygenäse 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. 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. 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.