Additional Information
Book Details
Abstract
Safely and effectively treat a full range of skin disorders with Comprehensive Dermatologic Drug Therapy, 3rd Edition! This trusted dermatology reference provides concise, complete, up-to-date guidance on today's full spectrum of topical, intralesional, and systemic drugs. Dr. Steven E. Wolverton and a team of leading international experts clearly explain what drugs to use, when to use them, and what to watch out for.
- Consult this title on your favorite e-reader with intuitive search tools and adjustable font sizes. Elsevier eBooks provide instant portable access to your entire library, no matter what device you’re using or where you’re located.
- Prescribe with confidence thanks to quick-access summaries of indications/contraindications, dosage guidelines, drug interactions, drug monitoring guidelines, adverse effects, and treatment protocols.
- Assess your knowledge and prepare for certification or recertification with more than 800 review questions and answers throughout.
- Contain costs and meet patient expectations with purchase information provided for major drugs.
- Quickly evaluate drug options for each disease discussed using a highly detailed, disease-specific index.
- Discover the best uses for new biologic therapeutics such as ustekinumab and rituximab, as well as newly improved TNF inhibitors.
- Offer your patients the very latest in cosmetic procedures, including chemical peels, intradermal fillers, and botulinum toxin.
- Use the safest and most effective drugs possible with new chapters on irritants and allergens in topical therapeutic agents, plus a new, separate chapter on mycophenolate mofetil.
- Review drugs recently taken off the market by the FDA, and use that knowledge to improve your current dermatologic drug therapy.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | cover | ||
| Comprehensive Dermatologic Drug Therapy | i | ||
| Copyright page | iv | ||
| Table of Contents | v | ||
| List of contributors | ix | ||
| Preface | xv | ||
| What is new? | xv | ||
| What is the same? | xv | ||
| What is ‘electronic’? | xv | ||
| Dedication | xvii | ||
| Acknowledgements | xix | ||
| From the UK (with Elsevier ties) | xix | ||
| From the ‘States’ (with Indiana University Department of Dermatology ties) | xix | ||
| From the ‘States’ and the World (the authors) | xix | ||
| A dozen suggestions to help the reader optimally utilize this book | xxi | ||
| References for drug interaction tables | xxii | ||
| I Introduction | 1 | ||
| 1 Basic principles of pharmacology | 1 | ||
| Introduction | 1 | ||
| Outline for the chapter | 1 | ||
| Pharmacokinetics – part I (Tables 1-2 and 1-3) | 2 | ||
| Drug absorption (The drug has to be absorbed and enter circulation) | 2 | ||
| Distribution (The drug has to travel to the site of intended action or to a reservoir) | 2 | ||
| Bioavailability (The drug has to be ‘available’ at the site of intended action) | 4 | ||
| Pharmacodynamics (the drug produces the desired pharmacologic effect) | 4 | ||
| Definitions (Table 1-4) | 4 | ||
| Drug receptors | 4 | ||
| Enzyme systems inhibited by drugs | 5 | ||
| Signal transduction and transcription factors | 5 | ||
| Pharmacokinetics – part II | 6 | ||
| Metabolism (The drug becomes more hydrophilic to favor renal and biliary excretion) | 6 | ||
| Excretion (The hydrophilic drug metabolites must leave the body) | 8 | ||
| Percutaneous absorption | 9 | ||
| General principles | 9 | ||
| Vehicles | 10 | ||
| Tachyphylaxis | 10 | ||
| Transdermal medication formulations | 11 | ||
| Bibliography: important reviews and chapters | 11 | ||
| Systemic drugs | 11 | ||
| Percutaneous absorption | 11 | ||
| 2 Principles for maximizing the safety of dermatologic drug therapy | 12 | ||
| Introduction | 12 | ||
| Anticipation | 13 | ||
| Patient selection | 13 | ||
| II Important Drug Regulatory Issues | 41 | ||
| 5 The FDA drug approval process | 41 | ||
| Introduction | 41 | ||
| Federal legislation for drug safety and efficacy | 41 | ||
| Food drug and cosmetic law | 41 | ||
| Kefauver–harris drug amendment | 41 | ||
| General testing required prior to marketing | 42 | ||
| Phase I–IV testing | 42 | ||
| Phase I testing | 42 | ||
| Phase II testing | 42 | ||
| Phase III testing | 42 | ||
| Pharmacovigilance process | 43 | ||
| Phase IV studies | 43 | ||
| Prescription Drug User Fee Act | 43 | ||
| FDA advisory panels | 43 | ||
| Off-label drug use | 43 | ||
| General principles | 43 | ||
| Food and Drug Administration Modernization Act | 43 | ||
| Generic drugs | 44 | ||
| Systemic drugs bioequivalence | 44 | ||
| Topical drug testing required | 44 | ||
| Special drug approval categories | 44 | ||
| Compassionate use regulations | 44 | ||
| Drug Price Competition and Patent Restoration Act | 44 | ||
| Orphan Drug Act | 44 | ||
| Related issues | 44 | ||
| Regulation of over the counter drugs, biologicals, and generics | 44 | ||
| Regulation of combination products | 44 | ||
| Comparisons of FDA regulation with other countries | 44 | ||
| Some final thoughts | 45 | ||
| Bibliography: important reviews | 45 | ||
| 6 Pharmacovigilance: | 46 | ||
| Introduction | 46 | ||
| Principle | 46 | ||
| III Systemic Drugs for Infectious Diseases | 61 | ||
| 8 Systemic Antibacterial Agents | 61 | ||
| Introduction | 61 | ||
| Penicillins | 62 | ||
| Pharmacology | 63 | ||
| Antimicrobial activity | 63 | ||
| Pharmacokinetics | 63 | ||
| Clinical use | 63 | ||
| Dermatologic uses (Table 8-2) | 63 | ||
| Antibacterial indications | 63 | ||
| Non-specific penicillin benefits | 63 | ||
| Adverse effects | 63 | ||
| Hypersensitivity reactions | 63 | ||
| Cross-reaction potential | 64 | ||
| Other important adverse effects | 64 | ||
| Drug interactions | 64 | ||
| Dosage | 64 | ||
| Cephalosporins | 64 | ||
| Cephalexin and many others | 64 | ||
| Pharmacology | 64 | ||
| Antimicrobial activity | 64 | ||
| First generation | 64 | ||
| Second generation | 65 | ||
| Third generation | 65 | ||
| Fourth generation | 66 | ||
| Fifth generation | 66 | ||
| Pharmacokinetics | 66 | ||
| Clinical use | 66 | ||
| Dermatologic indications | 66 | ||
| First generation | 67 | ||
| Second generation | 67 | ||
| Third generation | 67 | ||
| Fifth generation | 67 | ||
| Adverse effects | 67 | ||
| Hypersensitivity reactions and cross-reaction potential | 67 | ||
| Other adverse effects | 67 | ||
| Hematologic effects | 67 | ||
| Nephrotoxicity | 67 | ||
| IV Systemic Immunomodulatory and Antiproliferative Drugs | 143 | ||
| 12 Systemic corticosteroids | 143 | ||
| Systemic corticosteroids | 143 | ||
| Pharmacology (Table 12-1) | 143 | ||
| Structure | 143 | ||
| Absorption and distribution | 145 | ||
| Metabolism and excretion | 145 | ||
| Mechanism of action | 145 | ||
| Normal HPA axis function | 145 | ||
| Glucocorticoid effects (Table 12-4) | 145 | ||
| Mineralocorticoid effects (Table 12-4) | 147 | ||
| Glucocorticoid Receptor Physiology and Corticosteroid Resistance | 147 | ||
| Corticosteroids and Transcription Factors | 148 | ||
| Corticosteroid-induced apoptosis | 148 | ||
| Clinical use | 149 | ||
| FDA-Approved Indications and Off-Label Dermatologic Uses | 149 | ||
| Pemphigus vulgaris | 149 | ||
| Bullous pemphigoid | 150 | ||
| Cicatricial pemphigoid (mucous membrane pemphigoid) | 151 | ||
| Stevens–Johnson syndrome and toxic epidermal necrolysis | 151 | ||
| Erythema multiforme minor | 152 | ||
| Lupus erythematosus | 152 | ||
| Dermatomyositis | 152 | ||
| Vasculitis | 152 | ||
| Pyoderma gangrenosum | 152 | ||
| Acute dermatitis | 153 | ||
| Lichen planus | 153 | ||
| Sarcoidosis | 153 | ||
| Androgen excess syndromes | 153 | ||
| Postherpetic neuralgia | 153 | ||
| Intramuscular corticosteroid administration | 154 | ||
| Background issues | 154 | ||
| HPA-axis suppression | 154 | ||
| General dosing strategies | 154 | ||
| Pulse intravenous corticosteroid administration | 154 | ||
| General philosophy and dosing strategies | 154 | ||
| Specific disease indications | 155 | ||
| Risks of pulse IV CS | 155 | ||
| Summary | 155 | ||
| Adverse effects | 155 | ||
| General points regarding tables for adverse effects | 155 | ||
| Potentially fatal complications | 155 | ||
| Pregnancy risk | 157 | ||
| Other adverse effects with the potential for serious morbidity | 158 | ||
| HPA-axis suppression | 159 | ||
| Adrenal insufficiency – definitions | 159 | ||
| HPA-axis suppression – overview | 160 | ||
| Alternate means of stress responsiveness (see Box 12-1 HPA axis in a nutshell) | 160 | ||
| Laboratory tests of HPA axis function (Table 12-12) | 160 | ||
| Adrenal crisis and steroid withdrawal syndrome (SWS) | 161 | ||
| Stress corticosteroid doses – historical perspective | 161 | ||
| Stress corticosteroid doses – newer perspective | 162 | ||
| Drug interactions | 162 | ||
| Monitoring guidelines (Box 12-6 and Table 12-15) | 162 | ||
| Therapeutic guidelines | 163 | ||
| Individualized risk–benefit analysis | 163 | ||
| Acute dosage options | 163 | ||
| Corticosteroid dosing principles for children | 164 | ||
| Corticosteroid formulation choice | 164 | ||
| Tapering principles (Q12-11 Box 12-8) | 164 | ||
| Alternate-day corticosteroid therapy | 165 | ||
| Patient involvement in the therapeutic process | 165 | ||
| Systemic corticosteroids chapter update | 165 | ||
| Miscellaneous issues | 166 | ||
| Frequency of use of CS in general | 166 | ||
| Mechanism of action | 166 | ||
| Metabolism from inactive to active form of various CS | 166 | ||
| Segra (selective glucocorticoid receptor agonists) | 166 | ||
| HPA axis issues | 166 | ||
| Perioperative ‘stress’ doses of CS | 166 | ||
| Timing of CS administration | 166 | ||
| Adverse effects | 166 | ||
| Lipodystrophy and related metabolic syndrome changes | 166 | ||
| High frequency of mood and thought disorders | 166 | ||
| High frequency of menstrual abnormalities | 166 | ||
| Optimal combination of half-life and sodium retention | 166 | ||
| Tuberculosis risk and screening | 167 | ||
| Very low doses of CS and osteoporosis-related fracture risk | 167 | ||
| Osteonecrosis with short courses of CS | 167 | ||
| Bibliography: Important Reviews and Chapters | 167 | ||
| Basic science and pharmacology | 167 | ||
| Adverse effects overviews | 167 | ||
| Mechanisms of action | 167 | ||
| References (Reviews) for Chapter Update Section* | 168 | ||
| Web references | 168.e1 | ||
| Introduction and pharmacology | 168.e1 | ||
| Mechanisms of action | 168.e1 | ||
| Clinical use – pemphigus vulgaris | 168.e1 | ||
| Pemphigus in children, paraneoplastic pemphigus | 168.e1 | ||
| Bullous pemphigoid | 168.e1 | ||
| Cicatricial pemphigoid | 168.e2 | ||
| Herpes gestationis | 168.e2 | ||
| Other autoimmune bullous dermatoses | 168.e2 | ||
| Stevens-Johnson syndrome and TEN | 168.e2 | ||
| Lupus erythematosus | 168.e2 | ||
| Dermatomyositis | 168.e2 | ||
| Vasculitis | 168.e2 | ||
| Pyoderma gangrenosum | 168.e2 | ||
| Behçet’s disease and Sweet’s syndrome | 168.e2 | ||
| Dermatitis | 168.e2 | ||
| Lichen planus | 168.e3 | ||
| Sarcoidosis | 168.e3 | ||
| Other dermatoses | 168.e3 | ||
| Herpes zoster | 168.e3 | ||
| Intramuscular corticosteroids | 168.e3 | ||
| Pulse intravenous corticosteroids | 168.e3 | ||
| Adverse effects – general | 168.e3 | ||
| Bowel and peptic ulcer perforation | 168.e3 | ||
| Pancreatitis | 168.e4 | ||
| Diabetic complications | 168.e4 | ||
| Infectious complications | 168.e4 | ||
| Corticosteroids in pregnancy | 168.e4 | ||
| HPA axis suppression | 168.e4 | ||
| Therapeutic guidelines | 168.e4 | ||
| 13 Methotrexate | 169 | ||
| Introduction | 169 | ||
| Pharmacology | 169 | ||
| Structure | 169 | ||
| Absorption and distribution | 169 | ||
| Metabolism and excretion | 170 | ||
| Mechanism of action | 170 | ||
| Dna synthesis effects | 170 | ||
| T-cell effects | 171 | ||
| Immunosuppressive effects | 171 | ||
| Anti-inflammatory effects | 171 | ||
| Folic acid effects on methotrexate therapy | 171 | ||
| Clinical use | 172 | ||
| Indications | 172 | ||
| FDA-approved dermatologic indications | 172 | ||
| Psoriasis | 172 | ||
| Off-label dermatologic uses | 174 | ||
| Other proliferative disorders | 174 | ||
| Immunobullous dermatoses | 174 | ||
| Autoimmune connective tissue diseases | 174 | ||
| Vasculitis and neutrophilic dermatoses | 174 | ||
| Other dermatoses | 175 | ||
| Summary of ‘off-label’ dermatology indications | 175 | ||
| Adverse effects | 175 | ||
| Hepatotoxicity | 175 | ||
| Pulmonary toxicity | 176 | ||
| Hematologic effects | 176 | ||
| Malignancy induction | 177 | ||
| Gastrointestinal effects | 177 | ||
| Reproductive effects | 177 | ||
| Renal effects | 177 | ||
| Other adverse effects | 177 | ||
| Drug interactions | 178 | ||
| Monitoring guidelines (Box 13-3) | 178 | ||
| General issues and risk-factor assessment | 178 | ||
| Liver biopsy | 178 | ||
| Laboratory monitoring | 180 | ||
| Therapeutic guidelines | 180 | ||
| Bibliography: Important Reviews and Chapters | 181 | ||
| Pharmacology | 181 | ||
| Dermatology guidelines | 181 | ||
| Adverse effects overviews | 181 | ||
| Rheumatology viewpoint on methotrexate | 181 | ||
| References* | 181 | ||
| Web references | 181.e1 | ||
| Introduction and pharmacology | 181.e1 | ||
| Clinical use – approved indications | 181.e1 | ||
| Indications – proliferative dermatoses | 181.e1 | ||
| Indications – bullous dermatoses | 181.e1 | ||
| Indications – autoimmune connective tissue diseases | 181.e1 | ||
| Indications – vasculitis and neutrophilic dermatoses | 181.e2 | ||
| Other indications. | 181.e2 | ||
| Hepatotoxicity | 181.e2 | ||
| Pulmonary toxicity | 181.e2 | ||
| Hematologic toxicity | 181.e3 | ||
| Malignancy induction | 181.e3 | ||
| Other adverse effects | 181.e3 | ||
| Monitoring and therapeutic guidelines | 181.e3 | ||
| 14 Azathioprine | 182 | ||
| Introduction | 182 | ||
| Pharmacology | 182 | ||
| Absorption and distribution | 182 | ||
| Metabolism and excretion | 182 | ||
| Three pathways for azathioprine metabolism (Table 14-3) | 182 | ||
| Thiopurine methyltransferase polymorphism | 183 | ||
| Xanthine oxidase catabolic pathway | 184 | ||
| HGPRT anabolic pathway | 184 | ||
| Azathioprine dosing based on TPMT activity | 184 | ||
| Mechanism of action | 184 | ||
| Clinical use | 184 | ||
| Off-label dermatologic uses | 184 | ||
| Immunobullous dermatoses | 185 | ||
| Vasculitis | 185 | ||
| Neutrophilic dermatoses | 185 | ||
| Autoimmune connective tissue diseases | 185 | ||
| Dermatitis and papulosquamous dermatoses | 185 | ||
| Photodermatoses | 185 | ||
| Other dermatoses | 186 | ||
| Contraindications | 186 | ||
| Adverse effects (Box 14-3) | 186 | ||
| Immunosuppression carcinogenesis | 186 | ||
| Myelosuppression | 186 | ||
| Risk of infection | 186 | ||
| Vaccinations | 187 | ||
| Pregnancy, lactation, and fertility | 187 | ||
| Hypersensitivity syndrome | 187 | ||
| Gastrointestinal effects | 187 | ||
| Hepatic effects | 187 | ||
| Drug interactions (Table 14-4) | 187 | ||
| Monitoring guidelines | 188 | ||
| Summary | 188 | ||
| Bibliography: Important Reviews and Chapters | 189 | ||
| Azathioprine prescribing guidelines | 189 | ||
| Immunosuppressive and cytotoxic drug overviews (including azathioprine) | 189 | ||
| Thiopurine methyltransferase – overview | 189 | ||
| Adverse effects – carcinogenesis | 189 | ||
| References* | 189 | ||
| Web References | 189.e1 | ||
| Introduction | 189.e1 | ||
| Pharmacology – metabolism overview | 189.e1 | ||
| Thiopurine methyltransferase polymorphism | 189.e1 | ||
| Azathioprine dosing based on TPMT activity | 189.e1 | ||
| Mechanism of action | 189.e1 | ||
| Clinical use – immunobullous dermatoses | 189.e1 | ||
| Vasculitis | 189.e1 | ||
| Neutrophilic dermatoses | 189.e1 | ||
| Autoimmune connective tissue diseases | 189.e1 | ||
| Dermatitis and papulosquamous dermatoses | 189.e1 | ||
| Photodermatoses | 189.e1 | ||
| Other dermatoses | 189.e1 | ||
| Adverse effects – carcinogenesis | 189.e1 | ||
| Miscellaneous adverse effects | 189.e2 | ||
| Hypersensitivity syndrome | 189.e2 | ||
| Gastrointestinal and hepatic adverse effects | 189.e2 | ||
| Drug interactions | 189.e2 | ||
| 15 Mycophenolate mofetil and mycophenolic acid | 190 | ||
| Introduction | 190 | ||
| Pharmacology | 190 | ||
| Mechanism of action | 191 | ||
| Clinical use | 192 | ||
| Off-label dermatologic uses | 192 | ||
| Psoriasis | 192 | ||
| Immunobullous disease | 193 | ||
| Pemphigus | 193 | ||
| Other immunobullous dermatoses | 193 | ||
| AUTOIMMUNE CONNECTIVE TISSUE DISEASE | 193 | ||
| Lupus erythematosus | 193 | ||
| Dermatomyositis | 193 | ||
| Vasculitis | 193 | ||
| Systemic sclerosis | 194 | ||
| Atopic dermatitis | 194 | ||
| Contraindications | 194 | ||
| Adverse effects | 194 | ||
| Carcinogenicity | 194 | ||
| GI toxicity | 195 | ||
| Hematologic | 195 | ||
| Infectious | 195 | ||
| Pregnancy | 195 | ||
| Drug interactions | 195 | ||
| Treatment guidelines | 197 | ||
| Monitoring guidelines | 197 | ||
| Bibliography: Important Reviews and Chapters | 198 | ||
| References* | 198 | ||
| Web References | 198.e1 | ||
| Introduction | 198.e1 | ||
| Pharmacology | 198.e1 | ||
| Mechanism of action | 198.e1 | ||
| Psoriasis | 198.e1 | ||
| Pemphigus | 198.e1 | ||
| Other immunobullous diseases | 198.e1 | ||
| Lupus erythematosus | 198.e2 | ||
| Dermatomyositis | 198.e2 | ||
| Vasculitis | 198.e2 | ||
| Systemic sclerosis | 198.e2 | ||
| Atopic dermatitis | 198.e2 | ||
| Carcinogenicity | 198.e2 | ||
| Gastrointestinal and hematologic adverse effects | 198.e3 | ||
| Infectious adverse effects | 198.e3 | ||
| Drug interactions | 198.e3 | ||
| Monitoring and treatment guidelines | 198.e3 | ||
| Additional dermatoses not discussed in text | 198.e3 | ||
| 16 Cyclosporine | 199 | ||
| Introduction | 199 | ||
| Pharmacology | 199 | ||
| Structure | 199 | ||
| Absorption and Bioavailability | 199 | ||
| Metabolism and Excretion | 200 | ||
| Mechanism of Action | 200 | ||
| Clinical Use | 200 | ||
| FDA-approved indication | 200 | ||
| Psoriasis | 200 | ||
| Off-Label Dermatologic Uses | 202 | ||
| Atopic dermatitis | 202 | ||
| Pyoderma gangrenosum | 202 | ||
| Chronic idiopathic urticaria | 204 | ||
| Contraindications | 204 | ||
| Adverse Effects | 204 | ||
| Renal effects | 204 | ||
| Hypertension | 204 | ||
| Malignancy risk | 204 | ||
| Hyperlipidemia | 205 | ||
| Other adverse effects | 205 | ||
| Drug Interactions | 205 | ||
| Monitoring Guidelines | 205 | ||
| CsA blood levels | 205 | ||
| Hypertension | 205 | ||
| Renal function monitoring | 206 | ||
| Therapeutic Guidelines | 207 | ||
| Baseline assessment | 207 | ||
| Dosage and Treatment Regimens | 207 | ||
| Conversion from Sandimmune to neoral formulation | 209 | ||
| Sequential therapy involving cyclosporine and acitretin | 209 | ||
| Sequential therapy with other systemic therapies | 209 | ||
| Summary | 210 | ||
| Bibliography: Important Reviews and Chapters | 210 | ||
| General overviews | 210 | ||
| Consensus statements | 210 | ||
| Adverse effects overviews | 210 | ||
| References* | 211 | ||
| Web References | 211.e1 | ||
| Introduction | 211.e1 | ||
| Pharmacology | 211.e1 | ||
| Psoriasis (see also references 74–82) | 211.e1 | ||
| Monitoring and therapeutic guidelines – psoriasis | 211.e1 | ||
| Lichen planus | 211.e1 | ||
| Bullous dermatoses | 211.e1 | ||
| Autoimmune connective tissue diseases | 211.e1 | ||
| Neutrophilic dermatoses | 211.e1 | ||
| Atopic dermatitis | 211.e1 | ||
| Alopecia | 211.e1 | ||
| Granulomatous dermatoses | 211.e1 | ||
| Disorders of keratinization | 211.e2 | ||
| Photosensitivity dermatoses | 211.e2 | ||
| Other dermatoses | 211.e2 | ||
| Urticaria | 211.e2 | ||
| Contraindications | 211.e2 | ||
| Adverse effects – renal and hypertension | 211.e2 | ||
| Malignancy Risk | 211.e2 | ||
| Miscellaneous issues | 211.e2 | ||
| 17 Cytotoxic agents | 212 | ||
| Introduction | 212 | ||
| Major subcategories of cytotoxic agents and the cell cycle | 212 | ||
| Patient education issues | 213 | ||
| Antimetabolites | 214 | ||
| Thioguanine | 214 | ||
| Pharmacology (Table 17-2) | 214 | ||
| Mechanism of Action | 214 | ||
| Clinical Use | 215 | ||
| Off-Label Dermatologic Uses | 215 | ||
| Psoriasis | 215 | ||
| Contraindications | 215 | ||
| Adverse Effects | 215 | ||
| Myelosuppression | 215 | ||
| Gastrointestinal effects | 215 | ||
| Drug Interactions | 215 | ||
| Monitoring Guidelines | 216 | ||
| Therapeutic Guidelines | 216 | ||
| Hydroxyurea | 216 | ||
| Pharmacology (Table 17-2) | 216 | ||
| Mechanism of Action | 216 | ||
| Clinical Use | 216 | ||
| Psoriasis | 217 | ||
| Contraindications | 217 | ||
| Adverse Effects | 217 | ||
| Myelosuppression | 217 | ||
| Cutaneous adverse effects | 217 | ||
| Other adverse effects | 218 | ||
| Drug Interactions | 218 | ||
| Monitoring Guidelines | 218 | ||
| Therapeutic Guidelines | 218 | ||
| Alkylating agents | 218 | ||
| Cyclophosphamide | 219 | ||
| Pharmacology | 219 | ||
| Mechanism of Action | 219 | ||
| Clinical Use | 219 | ||
| Vasculitis | 220 | ||
| Mucous membrane pemphigoid (Cicatricial pemphigoid) | 221 | ||
| Pemphigus | 221 | ||
| Contraindications | 221 | ||
| Adverse Effects | 221 | ||
| Hemorrhagic cystitis and bladder cancer | 221 | ||
| Carcinogenesis | 222 | ||
| Other adverse effects | 222 | ||
| Drug Interactions | 222 | ||
| Monitoring Guidelines | 223 | ||
| Therapeutic Guidelines | 224 | ||
| Chlorambucil | 224 | ||
| Pharmacology | 224 | ||
| Mechanism of Action | 224 | ||
| Clinical Use | 224 | ||
| Off Label Dermatologic Uses | 224 | ||
| Necrobiotic xanthogranuloma | 224 | ||
| Pyoderma grangrenosum | 224 | ||
| Contraindications | 225 | ||
| Adverse Effects | 225 | ||
| General adverse effects | 225 | ||
| Carcinogenesis | 225 | ||
| Drug Interactions | 226 | ||
| Monitoring Guidelines | 226 | ||
| Therapeutic Guidelines | 226 | ||
| Melphalan | 226 | ||
| Bibliography: Important Reviews and Chapters* | 227 | ||
| Web References | 227.e1 | ||
| Thioguanine | 227.e1 | ||
| Hydroxyurea | 227.e1 | ||
| Cyclophosphamide | 227.e2 | ||
| Chlorambucil | 227.e3 | ||
| Melphalan | 227.e4 | ||
| 18 Dapsone | 228 | ||
| Introduction | 228 | ||
| Pharmacology | 228 | ||
| Absorption and bioavailability | 228 | ||
| Metabolism (Figure 18-2) | 229 | ||
| Excretion | 230 | ||
| Mechanism of action (Table 18-3) | 230 | ||
| Neutrophil respiratory burst (Figure 18-3) | 230 | ||
| Neutrophil chemotaxis | 232 | ||
| Effect on eosinophils and monocytes | 232 | ||
| Effects of dapsone metabolites | 232 | ||
| Clinical use | 232 | ||
| Dermatologic indications – consistent efficacy | 232 | ||
| Dermatitis herpetiformis | 233 | ||
| Linear iga Bullous Dermatosis and Chronic Bullous Dermatosis of Childhood Q18-5 | 233 | ||
| Bullous eruption of systemic lupus erythematosus | 233 | ||
| Leprosy | 233 | ||
| Erythema elevatum diutinum | 233 | ||
| Other dermatologic indications – variable efficacy (Box 18-1) | 233 | ||
| Autoimmune bullous dermatoses | 234 | ||
| Vasculitis | 234 | ||
| Neutrophilic dermatoses | 234 | ||
| Other dermatoses | 234 | ||
| Contraindications (Box 18-1) | 234 | ||
| Adverse effects – pharmacologic | 234 | ||
| Hemolytic anemia | 234 | ||
| Methemoglobinemia | 235 | ||
| Measures to treat hemolysis and methemoglobinemia | 235 | ||
| Adverse effects – idiosyncratic | 236 | ||
| Agranulocytosis | 236 | ||
| PERIPHERAL NEUROPATHY | 236 | ||
| Other neurologic effects | 236 | ||
| Gastrointestinal effects | 236 | ||
| Dapsone hypersensitivity syndrome | 237 | ||
| Other cutaneous hypersensitivity eruptions | 237 | ||
| Cross-reactivity with sulfonamide antibiotics | 237 | ||
| Photosensitivity | 237 | ||
| Carcinogenesis | 237 | ||
| Pregnancy and lactation | 237 | ||
| Drug interactions (Table 18-4) | 237 | ||
| Monitoring guidelines (Box 18-3) | 237 | ||
| Therapeutic guidelines | 239 | ||
| Bibliography: Important Reviews and Chapters | 240 | ||
| References* | 240 | ||
| Web references | 240.e1 | ||
| Introduction and pharmacology | 240.e1 | ||
| Dapsone mechanisms of action | 240.e1 | ||
| Dermatitis herpetiformis | 240.e1 | ||
| Bullous systemic lupus erythematosus | 240.e1 | ||
| Leprosy | 240.e1 | ||
| Erythema elevatum diutinum | 240.e1 | ||
| Autoimmune bullous dermatoses | 240.e1 | ||
| Vasculitis | 240.e2 | ||
| Neutrophilic dermatoses | 240.e2 | ||
| Cutaneous lupus erythematosus | 240.e2 | ||
| Relapsing polychondritis | 240.e2 | ||
| Granuloma annulare | 240.e2 | ||
| Brown recluse spider bites | 240.e2 | ||
| Granuloma faciale | 240.e2 | ||
| Rosacea | 240.e2 | ||
| Panniculitis | 240.e2 | ||
| Other dermatoses | 240.e2 | ||
| Dapsone and sulfonamide cross-reactivity | 240.e2 | ||
| Hemolytic anemia and methemoglobinemia | 240.e2 | ||
| Agranulocytosis | 240.e2 | ||
| Peripheral neuropathy | 240.e2 | ||
| Other neurologic effects | 240.e3 | ||
| Gastrointestinal effects | 240.e3 | ||
| Dapsone hypersensitivity syndrome | 240.e3 | ||
| Other adverse effects | 240.e3 | ||
| Monitoring guidelines | 240.e3 | ||
| 19 Antimalarial agents | 241 | ||
| Introduction | 241 | ||
| Pharmacology | 241 | ||
| Structure | 241 | ||
| Absorption and bioavailability | 241 | ||
| Metabolism and excretion | 242 | ||
| Mechanism of action | 243 | ||
| Effects on photosensitivity dermatoses | 243 | ||
| Immunosuppressive effects | 243 | ||
| Anti-inflammatory effects | 243 | ||
| Other mechanisms of action | 243 | ||
| Clinical use | 243 | ||
| FDA-approved indications | 243 | ||
| Lupus erythematosus | 244 | ||
| Off-label uses | 244 | ||
| Porphyria cutanea tarda | 244 | ||
| Other photodermatoses | 244 | ||
| Granulomatous dermatoses | 245 | ||
| Benign lymphocytic infiltrates | 245 | ||
| Panniculitis | 245 | ||
| Other dermatoses | 245 | ||
| Psoriatic arthritis | 245 | ||
| Contraindications | 245 | ||
| Adverse effects | 246 | ||
| Retinopathy | 246 | ||
| Other ocular effects | 247 | ||
| Use in Children | 247 | ||
| Use in Pregnancy and Lactation | 247 | ||
| Miscellaneous systemic adverse effects | 247 | ||
| Cutaneous adverse effects | 247 | ||
| Acute poisoning | 248 | ||
| Monitoring guidelines70–72,107 | 248 | ||
| Drug interactions | 248 | ||
| Therapeutic guidelines | 248 | ||
| Treatment of PCT | 250 | ||
| Bibliography: important antimalarial reviews and chapters | 250 | ||
| Antimalarial overviews | 250 | ||
| References* | 251 | ||
| Web references | 251.e1 | ||
| Introduction and pharmacology | 251.e1 | ||
| Lupus erythematosus | 251.e1 | ||
| FDA-approved indications | 251.e1 | ||
| Off-label uses – porphyria cutanea tarda | 251.e1 | ||
| Other photosensitivity dermatoses | 251.e1 | ||
| Benign lymphocytic infiltrates | 251.e2 | ||
| Panniculitis | 251.e2 | ||
| Other dermatoses | 251.e2 | ||
| Psoriatic arthritis | 251.e2 | ||
| Risk in pregnancy | 251.e2 | ||
| Other contraindications | 251.e2 | ||
| Adverse effects – ocular risk | 251.e2 | ||
| Use in pregnancy and in children | 251.e2 | ||
| Miscellaneous systemic adverse effects | 251.e2 | ||
| Cutaneous adverse effects | 251.e3 | ||
| Poisoning | 251.e3 | ||
| Monitoring and therapeutic guidelines | 251.e3 | ||
| 20 Systemic retinoids | 252 | ||
| Introduction and historical perspective | 252 | ||
| Pharmacology | 253 | ||
| Vitamin A physiology | 253 | ||
| Structure | 254 | ||
| Absorption and distribution | 254 | ||
| Metabolism and excretion | 254 | ||
| General aspects | 254 | ||
| Acitretin re-esterification (reverse metabolism) | 255 | ||
| Mechanism of retinoid action | 255 | ||
| Transport of Retinoids | 255 | ||
| Mechanism at the Nuclear Level | 255 | ||
| Clinical use | 255 | ||
| Practical considerations | 256 | ||
| FDA-approved indications | 256 | ||
| Psoriasis – retinoids as monotherapy | 256 | ||
| Psoriasis – Retinoids in Combination Therapy | 257 | ||
| Retinoids in Combination with Biologic Agents | 257 | ||
| Acne vulgaris | 257 | ||
| CTCL – Mycosis Fungoides and Sézary Syndrome | 258 | ||
| Off-label dermatologic uses | 258 | ||
| Rosacea | 258 | ||
| Hidradenitis Suppurativa and Dissecting Cellulitis of the Scalp | 258 | ||
| Darier’s disease | 258 | ||
| Pityriasis rubra pilaris | 258 | ||
| Ichthyosiform dermatoses | 258 | ||
| Chemoprevention of Malignancy | 258 | ||
| Lupus erythematosus | 259 | ||
| Lichen planus | 259 | ||
| Chronic hand eczema | 259 | ||
| Adverse effects | 259 | ||
| Teratogenicity – Women Exposed to Retinoids | 260 | ||
| Teratogenicity – Males Exposed to Retinoids | 260 | ||
| The ‘iPledge’ Registry Requirements and an Update After the First Year of the Program | 261 | ||
| Mucocutaneous adverse effects | 261 | ||
| Lipid effects | 261 | ||
| Depression | 262 | ||
| Inflammatory bowel disease | 262 | ||
| Bone effects | 263 | ||
| Ocular effects | 263 | ||
| Liver effects | 264 | ||
| Thyroid effects | 264 | ||
| Central nervous system effects | 264 | ||
| Muscle effects | 264 | ||
| Hair and Nail Effects | 264 | ||
| Hematologic effects | 264 | ||
| Drug interactions | 264 | ||
| Monitoring guidelines | 264 | ||
| Therapeutic guidelines | 267 | ||
| Acknowldgment | 267 | ||
| Bibliography: Important Reviews and Chapters | 268 | ||
| Drug category overviews | 268 | ||
| Specific retinoids | 268 | ||
| Retinoid chemoprevention of malignancies | 268 | ||
| Adverse effects overviews and monitoring guidelines | 268 | ||
| References* | 268 | ||
| Web references | 268.e1 | ||
| Introduction and historical perspective | 268.e1 | ||
| Pharmacology | 268.e1 | ||
| Mechanism of action | 268.e1 | ||
| Psoriasis – monotherapy | 268.e1 | ||
| Psoriasis – combination therapy | 268.e1 | ||
| Acne | 268.e1 | ||
| Cutaneous T-cell lymphoma | 268.e2 | ||
| V Drugs Used in Conjunction with Ultraviolet or Visible Light | 279 | ||
| 22 PUVA photochemotherapy and other phototherapy modalities | 279 | ||
| Introduction and drug history | 279 | ||
| Puva photochemotherapy | 279 | ||
| Pharmacology | 279 | ||
| Structure | 280 | ||
| Absorption | 280 | ||
| Bioavailability | 280 | ||
| Metabolism | 281 | ||
| Excretion | 281 | ||
| Photochemistry | 281 | ||
| Mechanism of action | 281 | ||
| Suppression of DNA Synthesis | 281 | ||
| Photoimmunologic effects | 281 | ||
| Selective cytotoxicity | 281 | ||
| Stimulation of Melanocytes | 281 | ||
| Summary | 281 | ||
| Clinical use | 281 | ||
| FDA-approved indications | 281 | ||
| Psoriasis | 281 | ||
| Vitiligo | 281 | ||
| Off-label dermatologic uses | 282 | ||
| Cutaneous T-cell Lymphoma | 282 | ||
| Other cutaneous malignancies | 282 | ||
| Dermatitis and Papulosquamous Dermatoses | 282 | ||
| Photosensitivity dermatoses | 282 | ||
| Other pruritic dermatoses | 283 | ||
| Other immunologic dermatoses | 283 | ||
| Miscellaneous dermatoses | 283 | ||
| Contraindications | 283 | ||
| Treatment procedure | 283 | ||
| Methoxsalen administration | 283 | ||
| UVA radiation | 283 | ||
| Clearance schedule | 284 | ||
| Maintenance schedule | 284 | ||
| Adjunctive treatment | 284 | ||
| Combination treatments | 284 | ||
| Protection | 284 | ||
| Short-term adverse effects | 285 | ||
| Long-term adverse effects | 285 | ||
| Non-melanoma skin cancer risk | 285 | ||
| Melanoma risk | 286 | ||
| Other long-term risks | 286 | ||
| Drug interactions | 286 | ||
| Monitoring guidelines (Box 22-8) | 286 | ||
| Therapeutic guidelines | 286 | ||
| Other forms of PUVA therapy | 286 | ||
| Narrowband UVB phototherapy | 287 | ||
| Introduction | 287 | ||
| Clinical use | 287 | ||
| Psoriasis | 287 | ||
| Vitiligo | 287 | ||
| Neoplastic dermatoses | 287 | ||
| Atopic dermatitis | 287 | ||
| Photosensitivity dermatoses | 287 | ||
| Pruritus | 287 | ||
| Miscellaneous dermatoses | 287 | ||
| Contraindications | 287 | ||
| Treatment procedure | 287 | ||
| Protection | 288 | ||
| Adverse effects | 288 | ||
| UVA-1 phototherapy | 288 | ||
| Clinical use | 288 | ||
| ATOPIC ECZEMA/DERMATITIS | 289 | ||
| Scleroderma | 289 | ||
| Systemic lupus erythematosus | 289 | ||
| Contraindications | 289 | ||
| Treatment procedure | 289 | ||
| Adverse effects | 289 | ||
| Bibliography: Important Reviews and Chapters | 289 | ||
| Guidelines of care for PUVA | 289 | ||
| Puva indications | 289 | ||
| Puva safety issues | 289 | ||
| References* | 290 | ||
| Web references | 290.e1 | ||
| Introduction and pharmacology | 290.e1 | ||
| Clinical use – psoriasis | 290.e1 | ||
| Vitiligo | 290.e1 | ||
| Neoplastic | 290.e1 | ||
| Papulosquamous/dermatitis | 290.e1 | ||
| Photosensitivity dermatoses | 290.e1 | ||
| Other off-label uses | 290.e1 | ||
| Treatment procedure | 290.e2 | ||
| Adverse effects | 290.e2 | ||
| Non-melanoma skin cancer risk | 290.e2 | ||
| Controversy on possible melanoma risk (see also80–88) | 290.e2 | ||
| Cataract risk | 290.e2 | ||
| Drug interactions | 290.e2 | ||
| Need for long-term or intermittent therapy | 290.e2 | ||
| Other forms of PUVA photochemotherapy | 290.e2 | ||
| Narrowband UVB phototherapy | 290.e3 | ||
| UVA-1 phototherapy | 290.e3 | ||
| 23 Extracorporeal photochemotherapy (photopheresis) | 291 | ||
| Introduction | 291 | ||
| Treatment delivery and considerations | 291 | ||
| Pharmacology | 292 | ||
| Mechanism of action – ECP | 292 | ||
| Cutaneous T-cell lymphoma | 292 | ||
| Autoimmune dermatoses | 293 | ||
| Clinical use | 293 | ||
| FDA-approved indications | 293 | ||
| Cutaneous t-cell lymphoma | 293 | ||
| Monitoring CTCL Response to ECP (Box 23-3) | 294 | ||
| Combination Therapy in CTCL Patients | 294 | ||
| Other dermatologic uses – treatment of T-cell-mediated autoimmune dermatoses | 295 | ||
| Monitoring Response of Autoimmune Dermatoses to ECP | 295 | ||
| Graft-versus-host disease (GVHD) | 295 | ||
| Scleroderma | 296 | ||
| Erosive oral lichen planus | 296 | ||
| Pemphigus vulgaris and foliaceus | 296 | ||
| Epidermolysis bullosa acquisita | 297 | ||
| Adverse effects | 297 | ||
| Therapeutic guidelines | 298 | ||
| Bibliography: Important Reviews and Chapters | 298 | ||
| References* | 298 | ||
| Web references | 298.e1 | ||
| Mechanism of action – CTCL | 298.e1 | ||
| Mechanism of action – autoimmunity | 298.e1 | ||
| Clinical use – CTCL | 298.e1 | ||
| Scleroderma | 298.e1 | ||
| Pemphigus vulgaris | 298.e1 | ||
| Pemphigus foliaceous | 298.e1 | ||
| Epidermolysis bullosa acquisita | 298.e1 | ||
| Acute GVHD | 298.e1 | ||
| Chronic GVHD | 298.e1 | ||
| Nephrogenic systemic fibrosis | 298.e1 | ||
| Oral erosive lichen planus | 298.e2 | ||
| FDA-approved indications – CTCL | 298.e2 | ||
| Multimodality treatment in CTCL | 298.e2 | ||
| Monitoring ECP in CTCL | 298.e2 | ||
| Clinical use – GVHD | 298.e2 | ||
| Scleroderma | 298.e2 | ||
| Clinical use – other dermatoses | 298.e2 | ||
| Autoimmune blistering diseases | 298.e2 | ||
| 24 Photodynamic therapy | 299 | ||
| Introduction | 299 | ||
| Pharmacology | 299 | ||
| Structure | 299 | ||
| Absorption and bioavailability | 299 | ||
| Metabolism and elimination | 299 | ||
| Mechanisms of action | 300 | ||
| Factors influencing porphyrin accumulation and activation | 300 | ||
| Photochemical and photobiologic reactions | 300 | ||
| Mechanisms pertinent to various dermatoses treated | 300 | ||
| Formulations available | 300 | ||
| Aminolevulinic acid | 300 | ||
| Methyl aminolevulinate | 300 | ||
| Other | 301 | ||
| Clinical use | 301 | ||
| FDA-approved indications | 301 | ||
| Actinic keratosis | 301 | ||
| Off-label uses | 302 | ||
| Basal cell carcinoma | 302 | ||
| Squamous cell carcinoma in situ | 302 | ||
| ACNE | 302 | ||
| Photoaging | 302 | ||
| Other applications | 303 | ||
| Contraindications | 303 | ||
| Pregnancy and lactation | 303 | ||
| Children and adolescents | 303 | ||
| Carcinogenicity, mutagenicity and impairment of fertility | 303 | ||
| Precautions | 303 | ||
| Adverse effects | 303 | ||
| Phototoxic reactions – desired and excessive | 303 | ||
| Pigmentary abnormalities and hypersensitivity reactions | 303 | ||
| Systemic absorption potential | 303 | ||
| Drug interactions | 303 | ||
| Monitoring guidelines | 303 | ||
| General therapeutic guidelines for PDT treatment of actinic keratoses | 303 | ||
| Bibliography: important photodynamic therapy reviews and chapters | 304 | ||
| Historical perspective | 304 | ||
| Pharmacology | 304 | ||
| General overviews | 304 | ||
| Web References | 305.e1 | ||
| Introduction and pharmacology | 305.e1 | ||
| Clinical use – actinic keratoses | 305.e1 | ||
| Basal cell carcinomas | 305.e1 | ||
| Squamous cell carcinoma – in situ | 305.e1 | ||
| Acne vulgaris | 305.e1 | ||
| Photoaging | 305.e1 | ||
| Other off-label uses | 305.e1 | ||
| Sunscreens for protection post-PDT | 305.e1 | ||
| References* | 304 | ||
| VI Biological Therapeutics | 307 | ||
| 25 Tumor necrosis factor (TNF) inhibitors | 307 | ||
| Introduction – psoriasis pathogenesis | 307 | ||
| Etanercept | 309 | ||
| Pharmacology | 309 | ||
| Clinical use | 309 | ||
| FDA-approved indications (Box 25-131–63) | 309 | ||
| Plaque psoriasis | 309 | ||
| Off-label dermatologic uses | 310 | ||
| Contraindications | 311 | ||
| Adverse effects of etanercept | 311 | ||
| Anti-drug antibodies | 311 | ||
| Injection site reactions | 311 | ||
| Drug interactions | 311 | ||
| Monitoring guidelines | 311 | ||
| Therapeutic guidelines | 311 | ||
| Infliximab | 312 | ||
| Pharmacology | 312 | ||
| Clinical use | 312 | ||
| FDA-approved indications (Box 25-249,83–110) | 312 | ||
| Psoriatic arthritis and psoriasis | 312 | ||
| Off-label dermatologic uses | 313 | ||
| Contraindications | 313 | ||
| Adverse effects | 313 | ||
| Infusion reactions | 313 | ||
| Anti-drug antibodies | 313 | ||
| Hepatotoxicity | 313 | ||
| Drug interactions | 313 | ||
| Monitoring guidelines | 314 | ||
| Therapeutic guidelines | 314 | ||
| Adalimumab | 314 | ||
| Pharmacology | 314 | ||
| Clinical use | 314 | ||
| FDA-approved indications (Box 25-3) | 314 | ||
| Psoriasis | 314 | ||
| Off-label dermatologic uses | 315 | ||
| Contraindications | 315 | ||
| Adverse effects | 315 | ||
| Injection site reactions | 315 | ||
| Anti-drug antibodies | 315 | ||
| Drug interactions | 315 | ||
| Monitoring guidelines | 315 | ||
| Therapeutic guidelines | 315 | ||
| Adverse effects of the tnf blockers in general | 315 | ||
| Malignancy risk – lymphoma | 315 | ||
| Skin cancer risk | 316 | ||
| Malignancies in children | 316 | ||
| Infections | 316 | ||
| Neurological disease | 317 | ||
| Congestive heart failure | 317 | ||
| Autoimmunity | 317 | ||
| Hematologic toxicity | 317 | ||
| Monitoring guidelines | 317 | ||
| Bibliography: important reviews and chapters | 318 | ||
| Basic science overview with TNF inhibitors | 318 | ||
| TNF inhibitors overviews for psoriasis/psoriatic arthritis | 318 | ||
| Off label uses of TNF inhibitors | 318 | ||
| Risks of TNF therapy | 318 | ||
| Web References | 318.e1 | ||
| Introduction | 318.e1 | ||
| Etanercept – pharmacology | 318.e1 | ||
| Etanercept – clinical trials | 318.e1 | ||
| Etanercept – off-label uses | 318.e1 | ||
| Etanercept – contraindications | 318.e2 | ||
| Etanercept – adverse effects | 318.e2 | ||
| Infliximab – pharmacology | 318.e2 | ||
| Infliximab – clinical trials | 318.e2 | ||
| Infliximab – off-label uses | 318.e2 | ||
| Infliximab – adverse effects | 318.e3 | ||
| Adalimumab – pharmacology and clnical trials | 318.e3 | ||
| Adalimumab – off-label uses | 318.e3 | ||
| Adalimumab – adverse effects | 318.e4 | ||
| TNF blockers – adverse effects | 318.e4 | ||
| References* | 318 | ||
| 26 Interleukin 12/23 inhibitors | 319 | ||
| Introduction | 319 | ||
| Monoclonal antibody treatments | 319 | ||
| Mechanism of action – the interleukin-12/23 pathway | 321 | ||
| The interleukin-23 pathway (Th17 axis) | 321 | ||
| Targeting the interleukin-23 pathway (Th17 axis) | 323 | ||
| Interleukin-12/23 therapy | 324 | ||
| FDA approval | 324 | ||
| Ustekinumab | 326 | ||
| Pharmacology | 326 | ||
| Pharmacokinetics | 326 | ||
| Clinical use – ustekinumab | 326 | ||
| Efficacy | 326 | ||
| Adverse effects | 328 | ||
| Clinical trials data – ustekinumab | 328 | ||
| Immunological insight into biological therapy safety | 329 | ||
| Briakinumab | 330 | ||
| Pharmacology | 330 | ||
| Pharmacokinetics | 330 | ||
| Clinical use – briakinumab | 330 | ||
| Efficacy | 330 | ||
| Adverse effects | 330 | ||
| Clinical trials data – briakinumab | 330 | ||
| Considerations for interleukin treatment | 330 | ||
| Dosing schedules | 330 | ||
| Quality of life issues | 331 | ||
| Overview adverse effects – interleukin inhibitors | 331 | ||
| Infection and malignancy | 331 | ||
| Antibody formation and efficacy | 331 | ||
| The future: combination therapy and switching | 331 | ||
| Conclusions | 331 | ||
| Bibliography: important reviews and chapters | 332 | ||
| Pathogenesis of psoriasis | 332 | ||
| Ustekinumab | 332 | ||
| Briakinumab | 332 | ||
| Web References | 332.e1 | ||
| Psoriasis background | 332.e1 | ||
| Mechanisms of action – interleukin-12/23 pathway | 332.e1 | ||
| Mechanisms of action – interleukin-23 pathway (Th17 axis) | 332.e1 | ||
| Targeting the interleukin-23 pathway (Th17 axis) | 332.e1 | ||
| FDA approval of interleukin therapy | 332.e1 | ||
| Ustekinumab – pharmacokinetics, efficacy, and safety | 332.e2 | ||
| Immunological insights into biologic safety | 332.e2 | ||
| Briankinumab – pharmacokinetics, efficacy, and safety | 332.e2 | ||
| Considerations for interleukin treatment | 332.e2 | ||
| References* | 332 | ||
| 27 Rituximab and future biological therapies | 333 | ||
| Introduction | 333 | ||
| Rituximab | 333 | ||
| Pharmacology | 333 | ||
| Structure | 333 | ||
| Pharmacokinetics | 333 | ||
| Mechanism of action | 334 | ||
| Clinical use | 335 | ||
| FDA-approved indications (Box 27-1) | 335 | ||
| Off-label dermatologic indications | 335 | ||
| Pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus | 336 | ||
| Epidermolysis bullosa acquisita | 336 | ||
| Bullous pemphigoid | 336 | ||
| Mucous membrane (cicatricial) pemphigoid | 336 | ||
| Dermatomyositis | 337 | ||
| Cutaneous lupus erythematosus | 337 | ||
| Graft-versus-host disease (acute and chronic) | 337 | ||
| Vasculitis | 337 | ||
| Primary cutaneous B-cell lymphoma | 337 | ||
| Contraindications | 337 | ||
| Warning and precautions | 337 | ||
| General precautions | 337 | ||
| Special populations | 338 | ||
| Adverse effects | 338 | ||
| General issues | 338 | ||
| Infusion reactions | 338 | ||
| Tumor lysis syndrome | 338 | ||
| Infections | 338 | ||
| Cytopenias | 338 | ||
| Risk of malignancy | 338 | ||
| Antibodies to the drug | 338 | ||
| Drug interactions | 338 | ||
| Monitoring guidelines | 338 | ||
| Therapeutic guidelines | 338 | ||
| Administration and dosing | 338 | ||
| Long-term therapy | 339 | ||
| Combination therapy | 339 | ||
| Biologic therapies in development or recently approved | 339 | ||
| References* | 340 | ||
| Web References | 341.e1 | ||
| Clinical use – general | 341.e1 | ||
| Pemphigus | 341.e1 | ||
| Other bullous dermatoses | 341.e1 | ||
| Autoimmune connective tissue diseases | 341.e2 | ||
| Graft-versus-host disease | 341.e2 | ||
| Vasculitis | 341.e2 | ||
| Primary cutaneous B-cell lymphomas | 341.e2 | ||
| Warnings and precautions | 341.e2 | ||
| Adverse effects | 341.e3 | ||
| Combination therapies | 341.e3 | ||
| Biologic therapies in development | 341.e3 | ||
| VII Miscellaneous Systemic Drugs | 343 | ||
| 28 Antihistamines | 343 | ||
| Importance of histamine in skin diseases | 343 | ||
| Mast cell production of histamine | 343 | ||
| Histamine receptors and resultant effects | 343 | ||
| Antihistamine mechanism of action | 344 | ||
| Historical overview | 344 | ||
| First-generation antihistamines | 344 | ||
| Second-generation antihistamines | 344 | ||
| First-generation antihistamines | 345 | ||
| Pharmacology | 345 | ||
| Clinical use | 347 | ||
| Indications | 347 | ||
| Special points | 348 | ||
| Second-generation H1 antihistamines | 348 | ||
| Fexofenadine | 348 | ||
| VIII Topical Drugs for Infectious Diseases | 445 | ||
| 36 Topical Antibacterial Agents | 445 | ||
| Introduction | 445 | ||
| Drugs used for wound care and minor topical bacterial infections | 445 | ||
| Bacitracin | 445 | ||
| Pharmacology | 445 | ||
| Microbiologic activity (Table 36-1) | 445 | ||
| Clinical use | 445 | ||
| Dermatologic uses | 445 | ||
| Adverse effects | 447 | ||
| Polymyxin B | 448 | ||
| Pharmacology | 448 | ||
| Microbiologic activity (Table 36-1) | 448 | ||
| IX Topical Immunomodulatory and Antiproliferative Drugs | 487 | ||
| 40 Topical corticosteroids | 487 | ||
| Introduction | 487 | ||
| Pharmacology | 487 | ||
| Estimating TCS potency | 487 | ||
| Pharmacokinetics | 488 | ||
| Structure of the TCS molecules | 488 | ||
| Vehicle-related issues | 490 | ||
| Role of condition of skin in percutaneous absorption | 490 | ||
| Mechanism of action | 490 | ||
| General concepts | 490 | ||
| Anti-inflammatory effects | 491 | ||
| Antiproliferative and atrophogenic effects | 492 | ||
| Systemic effects | 492 | ||
| Clinical use | 492 | ||
| Indications | 492 | ||
| Atopic dermatitis | 492 | ||
| Discoid lupus erythematosus | 493 | ||
| Granuloma annulare | 493 | ||
| Lichen planus | 493 | ||
| Lichen sclerosus et atrophicus | 494 | ||
| Psoriasis – general approach | 494 | ||
| Psoriasis – scalp treatment | 494 | ||
| Psoriasis – combination of TCS with vitamin d products | 494 | ||
| Psoriasis – combination of TCS with other therapies | 494 | ||
| Psoriasis – effects of occlusion | 494 | ||
| Seborrheic dermatitis | 495 | ||
| Well’s syndrome | 495 | ||
| Bullous dermatoses | 495 | ||
| Erosive pustular dermatosis | 495 | ||
| Behçet’s disease | 495 | ||
| Pyoderma gangrenosum | 495 | ||
| Alopecia areata | 495 | ||
| Patch-stage cutaneous t-cell lymphoma | 495 | ||
| Vitiligo | 495 | ||
| Melasma | 496 | ||
| Other dermatologic uses | 496 | ||
| Adverse effects – systemic | 496 | ||
| Effects on growth and HPA axis function | 496 | ||
| Risk factors for systemic adverse effects | 496 | ||
| Tests of HPA axis function | 497 | ||
| TCS regimens that do not cause HPA axis suppression | 497 | ||
| Use of TCS in pregnancy and lactation | 497 | ||
| Adverse effects – local | 497 | ||
| General issues regarding local effects | 497 | ||
| Atrophy | 497 | ||
| Addiction/rebound syndrome and perioral dermatitis | 497 | ||
| Ocular effects | 497 | ||
| Allergic contact dermatitis due to TCS molecule | 498 | ||
| Tachyphylaxis | 498 | ||
| Other local adverse effects | 499 | ||
| Vehicle-related adverse effects | 499 | ||
| Therapeutic guidelines | 499 | ||
| Choosing a TCS preparation | 499 | ||
| Compounding using TCS | 502 | ||
| Supervising the TCS therapy | 502 | ||
| Bibliography: important reviews and chapters | 504 | ||
| General overviews | 504 | ||
| Adverse effects – overviews | 504 | ||
| References* | 504 | ||
| Web References | 504.e1 | ||
| Pharmacology | 504.e1 | ||
| Mechanisms of action – general concepts | 504.e1 | ||
| Mechanisms of action – anti-inflammatory effects | 504.e1 | ||
| Mechanisms of action – antiproliferative and atrophogenic effects | 504.e1 | ||
| Atopic dermatitis | 504.e2 | ||
| Discoid lupus erythematosus | 504.e2 | ||
| Granuloma annulare | 504.e2 | ||
| Lichen planus | 504.e2 | ||
| Lichen sclerosus et atrophicus | 504.e2 | ||
| Psoriasis – general approach | 504.e2 | ||
| Psoriasis – scalp treatment | 504.e2 | ||
| Psoriasis – combination of TCS and calcipotriene | 504.e2 | ||
| Psoriasis – combination of TCS with other therapies | 504.e3 | ||
| Psoriasis – effects of TCS occlusion | 504.e3 | ||
| Other inflammatory dermatoses | 504.e3 | ||
| Bullous dermatoses – pemphigus and pemphigoid | 504.e3 | ||
| Neutrophilic dermatoses – Behçet’s disease and pyoderma gangrenosum | 504.e3 | ||
| Alopecia areata | 504.e3 | ||
| Mycosis fungoides/cutaneous T-cell lymphoma | 504.e3 | ||
| Vitiligo | 504.e3 | ||
| Miscellaneous dermatoses | 504.e3 | ||
| Other dermatoses | 504.e3 | ||
| Systemic adverse effects – growth and HPA axis effects | 504.e4 | ||
| Risk factors for systemic adverse effects | 504.e4 | ||
| Local adverse effects – general issues | 504.e4 | ||
| Atrophy effects | 504.e4 | ||
| Addiction/rebound syndrome and perioral dermatitis | 504.e4 | ||
| Ocular effects | 504.e4 | ||
| Allergic contact dermatitis to TCS molecule | 504.e4 | ||
| Tachyphylaxis | 504.e4 | ||
| Other local adverse effects | 504.e5 | ||
| Adverse effects due to the TCS vehicle | 504.e5 | ||
| Therapeutic guidelines | 504.e5 | ||
| 41 Topical retinoids | 505 | ||
| Introduction | 505 | ||
| Pharmacology | 505 | ||
| Structure | 505 | ||
| Mechanism of action | 505 | ||
| Teratogenicity | 507 | ||
| All-trans retinol and all-trans retinoic acid | 507 | ||
| Adapalene | 509 | ||
| Tazarotene | 511 | ||
| Bexarotene | 511 | ||
| Alitretinoin (9-cis retinoic acid) | 512 | ||
| Clinical use | 512 | ||
| Indications | 512 | ||
| Acne vulgaris | 512 | ||
| Actinic keratoses | 514 | ||
| Photoaging | 514 | ||
| Pigmentary disorders | 514 | ||
| Dysplastic nevi | 515 | ||
| Plaque-type psoriasis | 515 | ||
| Cutaneous T-cell lymphoma (CTCL) | 515 | ||
| Aids-related kaposi’s sarcoma | 515 | ||
| Wound healing and keloids | 515 | ||
| Striae distensae | 516 | ||
| Oral leukoplakia and lichen planus | 516 | ||
| Other dermatoses | 516 | ||
| Cosmeceuticals | 516 | ||
| Adverse effects | 516 | ||
| Acknowledgement | 516 | ||
| Bibliography: important chapters and reviews | 517 | ||
| Specific topical retinoids | 517 | ||
| References* | 517 | ||
| Web references | 517.e1 | ||
| Introduction – drug development | 517.e1 | ||
| Pharmacology | 517.e1 | ||
| All-trans retinol and all-trans retinoic acid | 517.e1 | ||
| Adapalene | 517.e1 | ||
| Tazarotene | 517.e1 | ||
| Bexarotene | 517.e1 | ||
| Alitretinoin | 517.e1 | ||
| Clinical use – acne vulgaris | 517.e1 | ||
| Actinic keratosis | 517.e2 | ||
| Photoaging | 517.e2 | ||
| Pigmentary disorders/dysplastic nevi | 517.e2 | ||
| Psoriasis | 517.e2 | ||
| Cutaneous T-cell lymphoma | 517.e2 | ||
| AIDS-related kaposi’s sarcoma | 517.e2 | ||
| Wound healing and striae distensae | 517.e2 | ||
| Oral leukoplakia and lichen planus | 517.e3 | ||
| Other dermatoses | 517.e3 | ||
| 42 Topical and intralesional chemotherapeutic agents | 518 | ||
| Introduction | 518 | ||
| Topical chemotherapeutic agents | 518 | ||
| 5-Fluorouracil | 518 | ||
| Pharmacology | 518 | ||
| Mechanism of action | 518 | ||
| Clinical use | 519 | ||
| Indications | 519 | ||
| Actinic keratoses | 519 | ||
| Non-melanoma skin cancer | 520 | ||
| Actinic cheilitis | 520 | ||
| Keratoacanthomas | 520 | ||
| Warts | 520 | ||
| Porokeratosis | 520 | ||
| Contraindications | 520 | ||
| Adverse effects | 520 | ||
| Therapeutic guidelines | 520 | ||
| Mechlorethamine/nitrogen mustard | 521 | ||
| Pharmacology | 521 | ||
| Mechanism of action | 521 | ||
| Clinical use | 521 | ||
| Indications | 521 | ||
| Mycosis fungoides – the Stanford University experience | 521 | ||
| Mycosis fungoides – the New York University experience | 522 | ||
| Mycosis fungoides – the Temple University experience | 522 | ||
| Contraindications | 522 | ||
| Adverse effects | 522 | ||
| Contact dermatitis | 522 | ||
| Induction of secondary cutaneous malignancies | 522 | ||
| Pigment alteration | 522 | ||
| Therapeutic guidelines Q42-5 | 522 | ||
| Compounding nitrogen mustard solution | 522 | ||
| Compounding nitrogen mustard ointment | 522 | ||
| Treatment area | 522 | ||
| Treatment duration | 523 | ||
| Carmustine/BCNU | 523 | ||
| Pharmacology | 523 | ||
| Clinical use | 523 | ||
| Indications | 523 | ||
| Mycosis fungoides – study results with BCNU solution | 523 | ||
| Mycosis fungoides – study results with BCNU ointment | 523 | ||
| Contraindications | 523 | ||
| Adverse effects | 523 | ||
| Monitoring guidelines Q42-6 | 523 | ||
| Therapeutic guidelines | 523 | ||
| BCNU solution | 523 | ||
| BCNU ointment | 524 | ||
| Intralesional chemotherapeutic agents | 524 | ||
| Vinblastine | 524 | ||
| X Miscellaneous Topical Drugs | 551 | ||
| 46 Sunscreens | 551 | ||
| Introduction | 551 | ||
| Sunscreen options | 551 | ||
| Active sunscreen ingredients | 551 | ||
| UVB sunscreens | 553 | ||
| Padimate O | 553 | ||
| Octinoxate (octyl methoxycinnamate) | 554 | ||
| Octisalate (octyl salicylate) | 554 | ||
| Octocrylene | 554 | ||
| Ensulizole (phenylbenzimidazole sulfonic acid) | 554 | ||
| UVA sunscreens | 554 | ||
| Oxybenzone | 554 | ||
| Meradimate (menthyl anthranilate) | 554 | ||
| Avobenzone (butylmethoxydibenzoylmethane) | 554 | ||
| Ecamsule (tetraphthalydine dicamphor sulfonic acid) | 555 | ||
| Physical blockers | 555 | ||
| Titanium dioxide | 555 | ||
| Zinc oxide | 555 | ||
| Sunscreens pending approval | 555 | ||
| Clinical use | 555 | ||
| Indications | 555 | ||
| SPF level | 556 | ||
| UVA protection | 556 | ||
| Sunscreen vehicles | 556 | ||
| Emulsions | 557 | ||
| Gels | 557 | ||
| Sprays | 557 | ||
| Sticks | 557 | ||
| Cosmetics | 557 | ||
| Adverse effects | 557 | ||
| Subjective irritation | 557 | ||
| Contact urticaria | 558 | ||
| Irritant contact dermatitis | 558 | ||
| Allergic contact dermatitis | 558 | ||
| Photosensitivity | 558 | ||
| Acne induction and exacerbation | 558 | ||
| General photoprotection instructions for patients | 558 | ||
| Special patient group instructions | 559 | ||
| Photosensitive patients | 559 | ||
| Patients with sensitive skin | 559 | ||
| Acne-prone patients | 559 | ||
| Children | 559 | ||
| Theoretical inhibition of vitamin d synthesis | 559 | ||
| Sunless tanners – dihydroxyacetone | 559 | ||
| Summary | 560 | ||
| Bibliography: Important Reviews and Chapters | 561 | ||
| Web references | 561.e1 | ||
| Definitions and sunscreen options | 561.e1 | ||
| Clinical use | 561.e1 | ||
| Adverse effects | 561.e1 | ||
| Patient instructions | 561.e1 | ||
| References* | 561 | ||
| 47 Therapeutic shampoos | 562 | ||
| Introduction | 562 | ||
| Dermatoses involving the scalp | 562 | ||
| Seborrheic dermatitis and related scalp conditions | 562 | ||
| Psoriasis | 562 | ||
| Lichen simplex chronicus | 564 | ||
| Other scalp dermatoses | 564 | ||
| Historical perspective | 564 | ||
| Pharmacology | 564 | ||
| Mechanism of action Q47-2 | 564 | ||
| General properties of therapeutic shampoos | 564 | ||
| Keratolytic effects | 564 | ||
| Anti-inflammatory effects | 565 | ||
| Antiproliferative effects | 565 | ||
| Antipityrosporum effects | 565 | ||
| Systemic absorption | 565 | ||
| Clinical use | 566 | ||
| Indications | 566 | ||
| Adverse effects | 566 | ||
| Safety in pregnancy | 566 | ||
| Safety in children | 566 | ||
| Allergic and irritant contact dermatitis | 566 | ||
| Other adverse effects | 567 | ||
| Therapeutic guidelines | 567 | ||
| Application technique and frequency | 567 | ||
| Ketoconazole and ciclopirox | 567 | ||
| Selenium sulfide and zinc pyrithione | 567 | ||
| Salicylic acid and tar | 568 | ||
| Clobetasol propionate and fluocinolone acetonide | 568 | ||
| Chronic use of therapeutic shampoos | 568 | ||
| Rotational therapy | 568 | ||
| Adjunctive scalp therapy – topical and systemic | 568 | ||
| Role in tinea capitis | 568 | ||
| Prescription products | 568 | ||
| Drug interactions | 568 | ||
| Summary | 569 | ||
| Bibliography: important reviews and chapters | 569 | ||
| References* | 569 | ||
| Web references | 569.e1 | ||
| Introduction | 569.e1 | ||
| Mechanisms of action | 569.e1 | ||
| Systemic absorption | 569.e1 | ||
| Adverse effects | 569.e2 | ||
| Therapeutic guidelines | 569.e2 | ||
| 48 α-Hydroxy acids | 570 | ||
| Introduction | 570 | ||
| Pharmacology | 570 | ||
| Structure | 570 | ||
| Mechanism of action | 571 | ||
| Epidermal effects | 571 | ||
| Dermal effects | 571 | ||
| Polyhydroxy acids effects | 571 | ||
| Clinical use | 572 | ||
| Xerosis and ichthyosis | 572 | ||
| Rhytides and dermatoheliosis (photoaged skin) | 572 | ||
| Nail disorders | 574 | ||
| Acne vulgaris and related conditions | 574 | ||
| Rosacea | 574 | ||
| Hyperpigmentation | 574 | ||
| Actinic keratoses | 575 | ||
| Formulations | 575 | ||
| Bioavailability | 575 | ||
| Vehicle components and AHA absorption | 576 | ||
| Formulation Ph and irritancy | 576 | ||
| Formulation Ph and dermal/epidermal effects | 576 | ||
| Combination products | 576 | ||
| Prescription versus over-the-counter status | 576 | ||
| Adverse effects | 577 | ||
| Irritancy and pigmentary changes | 577 | ||
| Herpes simplex infections | 577 | ||
| Photosensitivity versus photoprotection | 577 | ||
| Summary | 577 | ||
| Bibliography: important reviews and chapters | 578 | ||
| References* | 578 | ||
| Web References | 578.e1 | ||
| Pharmacology | 578.e1 | ||
| Clinical use | 578.e1 | ||
| Formulations – cosmeceutical uses | 578.e1 | ||
| Adverse effects | 578.e1 | ||
| 49 Chemical peels | 579 | ||
| Introduction | 579 | ||
| Superficial chemical peels | 579 | ||
| α-Hydroxy acids | 579 | ||
| β-Hydroxy acids | 579 | ||
| Jessner’s solution | 580 | ||
| Medium-depth chemical peels | 580 | ||
| Combination peels | 580 | ||
| Monheit peel | 580 | ||
| Brody peel | 580 | ||
| Coleman peel | 580 | ||
| Deep chemical peels | 581 | ||
| Clinical use | 581 | ||
| Indications (Box 49-1) Q49-7 | 581 | ||
| Melasma | 581 | ||
| Photoaging | 581 | ||
| Acne vulgaris | 582 | ||
| Adverse effects (Box 49-2) | 582 | ||
| Persistent erythema | 582 | ||
| Pigmentary changes | 582 | ||
| Milia | 582 | ||
| Acneiform eruptions | 582 | ||
| Infections | 582 | ||
| Scarring | 582 | ||
| Cardiotoxicity | 582 | ||
| Use in pregnancy | 583 | ||
| Bibliography: important reviews and chapters | 583 | ||
| References* | 583 | ||
| Web References | 583.e1 | ||
| Introduction | 583.e1 | ||
| Superficial, intermediate, and deep chemical peels | 583.e1 | ||
| Indications | 583.e1 | ||
| Cardiac toxicity | 583.e1 | ||
| 50 Products for the care of chronic wounds | 584 | ||
| Introduction | 584 | ||
| Wound healing physiology and ideal wound healing environment | 584 | ||
| General approach to a patient with chronic wounds | 584 | ||
| Wound history | 584 | ||
| Past medical history | 585 | ||
| Past surgical history | 585 | ||
| Medication history | 585 | ||
| Social history | 585 | ||
| Review of systems | 585 | ||
| Physical examination | 585 | ||
| Laboratory evaluation | 585 | ||
| Culture | 585 | ||
| Imaging studies | 589 | ||
| Venous ulcer disease | 589 | ||
| Compression therapy for venous leg ulcers | 589 | ||
| General concepts of compression therapy | 589 | ||
| Unna boot plus primary dressing | 590 | ||
| Stretch bandages | 590 | ||
| Multilayer elastic bandages | 590 | ||
| Q50-7 Clinical trials concerning compression therapy for venous ulcers | 590 | ||
| Comparison between methods | 590 | ||
| Wound bed preparation | 590 | ||
| Wound care dressings used in venous ulcerations | 591 | ||
| Hydrocolloids | 591 | ||
| Foams | 591 | ||
| Alginates | 591 | ||
| Oasis | 591 | ||
| Apligraf | 591 | ||
| Periwound protectants | 593 | ||
| Systemic and surgical treatments | 593 | ||
| Pentoxifylline | 593 | ||
| Surgical therapy | 593 | ||
| Traditional surgical therapy | 593 | ||
| Endovascular ablation techniques | 593 | ||
| Growth factor therapy | 593 | ||
| Bibliography: important reviews and chapters | 594 | ||
| Treatment modalities in venous ulcers | 594 | ||
| Compression in venous ulcers | 594 | ||
| References* | 594 | ||
| Web References | 594.e1 | ||
| Introduction and wound healing | 594.e1 | ||
| Venous insufficiency and venous ulcers | 594.e1 | ||
| Compression in venous ulcers | 594.e1 | ||
| Wound bed preparation | 594.e1 | ||
| Treatment modalities in venous ulcers | 594.e1 | ||
| Presentation of different ulcers and treatment | 594.e1 | ||
| 51 Agents used for treatment of hyperkeratosis | 595 | ||
| Introduction | 595 | ||
| Salicylic acid | 595 | ||
| Pharmacology | 595 | ||
| Chemistry | 595 | ||
| Mechanism of action | 595 | ||
| Keratolytic and desmolytic effects | 595 | ||
| Sunscreen effects | 596 | ||
| Anti-inflammatory effects | 596 | ||
| Clinical use | 596 | ||
| Dermatologic uses | 596 | ||
| Verruca and calluses | 596 | ||
| Scalp psoriasis and seborrheic dermatitis | 596 | ||
| Ichthyosis and related conditions | 596 | ||
| Dermatophyte infections | 597 | ||
| Acne | 597 | ||
| Psoriasis (non-scalp) | 597 | ||
| Use in sunscreens | 597 | ||
| Pruritus and pain | 597 | ||
| Photoaging – chemical peels | 597 | ||
| Hyperkeratosis | 597 | ||
| Hyperhidrosis | 597 | ||
| Adverse effects | 597 | ||
| Systemic absorption – salicylism | 597 | ||
| Systemic absorption – hypoglycemia | 598 | ||
| Contact allergy | 598 | ||
| Sulfur | 598 | ||
| Pharmacology | 598 | ||
| Chemistry | 598 | ||
| Mechanism of action | 599 | ||
| Keratolytic and keratoplastic effects | 599 | ||
| Antifungal effects | 599 | ||
| Antibacterial effects | 599 | ||
| Antiparasitic effects | 599 | ||
| Pharmacokinetics | 599 | ||
| Clinical use | 599 | ||
| Dermatologic uses | 599 | ||
| Acne and rosacea | 599 | ||
| Scabies | 600 | ||
| Adverse effects | 600 | ||
| Tar | 600 | ||
| Pharmacology | 600 | ||
| Chemistry | 600 | ||
| Mechanism of action | 600 | ||
| Antiproliferative effects | 600 | ||
| Other effects of tar | 600 | ||
| Clinical use | 600 | ||
| Dermatologic uses | 600 | ||
| Psoriasis | 601 | ||
| Seborrheic dermatitis | 601 | ||
| Use of tar in compounding | 601 | ||
| Adverse effects | 601 | ||
| Possible carcinogenesis | 601 | ||
| Aesthetic issues | 601 | ||
| Phototoxicity | 601 | ||
| Contact allergy | 601 | ||
| Other adverse effects of tar | 601 | ||
| Urea | 602 | ||
| Pharmacology | 602 | ||
| Chemistry | 602 | ||
| Mechanism of action | 602 | ||
| General effects of urea | 602 | ||
| Keratolytic and hygroscopic/humectant effects | 602 | ||
| Clinical use | 602 | ||
| Dermatologic uses | 602 | ||
| Xerosis and hyperkeratosis | 602 | ||
| Chemical nail avulsion | 602 | ||
| Less common uses of urea | 603 | ||
| Adverse effects | 603 | ||
| Bibliography: important reviews and chapters | 603 | ||
| Salicylic acid | 603 | ||
| Sulfur | 603 | ||
| Tar | 603 | ||
| Urea | 603 | ||
| Web References | 603.e1 | ||
| Salicylic acid – pharmacology | 603.e1 | ||
| Salicylic acid – clinical use | 603.e1 | ||
| Salicylic acid – adverse effects | 603.e1 | ||
| Sulfur – pharmacology | 603.e1 | ||
| Sulfur – clinical use | 603.e2 | ||
| Sulfur – adverse effects | 603.e2 | ||
| Tar – history and pharmacology | 603.e2 | ||
| Tar – clinical use | 603.e2 | ||
| Tar – possible carcinogenicity | 603.e2 | ||
| Tar – other adverse effects | 603.e2 | ||
| Urea – history and pharmacology | 603.e2 | ||
| Urea – clinical use and adverse effects | 603.e2 | ||
| References* | 603 | ||
| 52 Cosmetic therapy | 604 | ||
| Cosmetic therapy overview | 604 | ||
| Skin bleaching agents | 604 | ||
| Hydroquinone | 604 | ||
| Skin pigmenting products – dihydroxyacetone | 604 | ||
| Facial foundations and camouflage cosmetics | 605 | ||
| Skin cleansers | 606 | ||
| Moisturizers | 607 | ||
| Hair shampoos | 608 | ||
| Hair permanent waving agents | 608 | ||
| Hair-straightening agents | 609 | ||
| Hair-dyeing agents | 610 | ||
| Gradual hair dyes | 610 | ||
| Temporary hair dyes | 610 | ||
| Semipermanent hair dyes | 610 | ||
| Permanent hair dyes | 610 | ||
| Hair-bleaching agents | 611 | ||
| Nail polish | 611 | ||
| Bibliography: important books | 612 | ||
| Web references | 612.e1 | ||
| Hydroquinone and mequinol | 612.e1 | ||
| Dihydroxyacetone | 612.e1 | ||
| Facial foundations/camouflage cosmetics | 612.e1 | ||
| Skin cleansers | 612.e1 | ||
| Moisturizers | 612.e1 | ||
| Hair shampoos | 612.e1 | ||
| Hair permanent waving agents | 612.e1 | ||
| Hair-straightening agents | 612.e1 | ||
| Hair-dyeing agents | 612.e1 | ||
| Hair-bleaching agents | 612.e1 | ||
| Nail polish | 612.e1 | ||
| 53 Irritants and allergens: | 613 | ||
| Introduction | 613 | ||
| Contact dermatitis: the concept | 613 | ||
| Allergic contact dermatitis | 613 | ||
| Irritant contact dermatitis | 613 | ||
| When to suspect contact dermatitis | 613 | ||
| Regional approach | 614 | ||
| Empirical recommendations | 614 | ||
| Scalp | 614 | ||
| Face | 614 | ||
| Eyelids | 614 | ||
| Lips and perioral | 615 | ||
| Neck | 616 | ||
| Hands | 616 | ||
| Feet | 616 | ||
| Anogenital | 617 | ||
| Stasis dermatitis and chronic leg ulcers | 618 | ||
| Final thoughts | 618 | ||
| Bibliography: important reviews and chapters | 619 | ||
| Web References | 619.e1 | ||
| References* | 619 | ||
| 54 Insect repellents | 620 | ||
| Introduction | 620 | ||
| Insect biology | 620 | ||
| General concepts | 620 | ||
| Stimuli that attract insects | 620 | ||
| Insect repellents overview | 622 | ||
| Chemical insect repellents | 622 | ||
| DEET | 622 | ||
| Formulation of available products | 622 | ||
| How to choose and apply DEET repellents | 622 | ||
| DEET concentration versus effectiveness | 622 | ||
| Guidelines for DEET | 622 | ||
| DEET and sunscreen combination products | 622 | ||
| Pharmacokenetics of DEET | 624 | ||
| Human toxicity of DEET | 624 | ||
| General aspects of safety profile | 624 | ||
| Pregnancy exposure risk | 624 | ||
| DEET neurotoxicity | 624 | ||
| DEET cardiovascular toxicity and allergic reactions | 624 | ||
| Large population-based DEET safety studies | 624 | ||
| Summary of DEET toxicity | 625 | ||
| Biopesticide repellents | 625 | ||
| IR3535 (ethyl-butylacetylaminoproprionate) | 625 | ||
| Piperidine (picaridin) | 625 | ||
| Plant-derived repellents | 625 | ||
| Citronella | 625 | ||
| Scientific testing of citronella-based products | 625 | ||
| Citronella candles and plants | 626 | ||
| Bite blocker | 626 | ||
| BioUD (2-undecanone) | 626 | ||
| Eucalyptus | 626 | ||
| Efficacy of DEET versus botanical repellents | 626 | ||
| Permethrin | 627 | ||
| Spectrum of protection | 627 | ||
| Formulations and product application | 627 | ||
| Related issues | 628 | ||
| Reducing local insect populations | 628 | ||
| Relief from arthropod bites | 628 | ||
| Bibliography: important reviews and chapters | 628 | ||
| Web References | 628.e1 | ||
| Arthropod physiology and behavior | 628.e1 | ||
| General issues – insect repellents | 628.e1 | ||
| DEET – clinical use | 628.e1 | ||
| DEET – pharmacokinetics | 628.e1 | ||
| DEET – pregnancy risk | 628.e1 | ||
| DEET – neurotoxicity | 628.e2 | ||
| DEET – cardiovascular effects | 628.e2 | ||
| DEET – allergic reactions | 628.e2 | ||
| DEET – miscellaneous articles and reviews | 628.e2 | ||
| Biopesticide repellents: IR3535 | 628.e2 | ||
| Biopesticide repellents: picaridin | 628.e2 | ||
| Botanical insect repellents | 628.e2 | ||
| Permethrin insecticides (including comparison with DEET) | 628.e3 | ||
| Tick repellents | 628.e3 | ||
| Related issues – reducing local insect populations | 628.e3 | ||
| Related issues – relief from arthropod bites | 628.e3 | ||
| References* | 628 | ||
| 55 Miscellaneous topical agents | 629 | ||
| Introduction | 629 | ||
| Topical antioxidants | 629 | ||
| Ascorbic acid (Vitamin C) | 629 | ||
| Pharmacology | 629 | ||
| Mechanism of action | 629 | ||
| Clinical use | 629 | ||
| Dermatologic uses | 629 | ||
| Photoaging | 629 | ||
| Photoprotection | 630 | ||
| Adverse effects | 630 | ||
| Therapeutic guidelines | 630 | ||
| Pregnancy prescribing status | 630 | ||
| Vitamin E | 630 | ||
| Pharmacology | 630 | ||
| XI Injectable and Mucosal Routes of Drug Administration | 637 | ||
| 56 Local anesthetics | 637 | ||
| Introduction | 637 | ||
| Injectable local anesthetics | 637 | ||
| Lidocaine and related amide anesthetics | 637 | ||
| Pharmacology | 637 | ||
| Structure | 637 | ||
| Absorption | 638 | ||
| Bioavailability | 639 | ||
| Metabolism | 639 | ||
| Excretion | 639 | ||
| Mechanism of action Q56-2 | 639 | ||
| Normal physiology of nerve conduction | 639 | ||
| Preventing nerve depolarization | 639 | ||
| Subcategories of nerve fibers | 640 | ||
| Clinical use | 641 | ||
| Fda-approved indications | 641 | ||
| Infiltrative anesthesia | 641 | ||
| Ring block | 642 | ||
| Regional nerve blocks | 642 | ||
| Off-label dermatologic uses | 642 | ||
| Tumescent anesthesia | 642 | ||
| Adverse effects | 642 | ||
| Toxic effects | 642 | ||
| Allergic reactions | 643 | ||
| Epinephrine effects | 643 | ||
| Reactions related to injection procedure | 644 | ||
| Drug interactions | 644 | ||
| Therapeutic guidelines | 644 | ||
| General guidelines for use | 644 | ||
| Use of local anesthetics during pregnancy | 645 | ||
| Topical anesthetics | 645 | ||
| Eutectic lidocaine and prilocaine (EMLA) | 645 | ||
| Pharmacology | 645 | ||
| Absorption | 645 | ||
| Metabolism and excretion | 645 | ||
| Clinical use | 645 | ||
| FDA-approved indications | 645 | ||
| Skin surgery | 645 | ||
| Laser surgery | 646 | ||
| Debridement of leg ulcers | 646 | ||
| Off-label dermatologic uses | 646 | ||
| Postherpetic neuralgia | 646 | ||
| Adverse effects | 646 | ||
| Systemic effects – methemoglobinemia | 646 | ||
| Other systemic effects | 647 | ||
| Local reactions | 647 | ||
| Therapeutic guidelines | 647 | ||
| Topical lidocaine | 647 | ||
| Benzocaine | 647 | ||
| Dyclonine | 647 | ||
| Other topical anesthetics – pramoxine and dibucaine | 647 | ||
| Co-injectable vasoconstrictors | 648 | ||
| Epinephrine | 648 | ||
| Pharmacology | 648 | ||
| Mechanism of action | 648 | ||
| Clinical use | 648 | ||
| FDA-approved indications | 648 | ||
| Hemostasis | 649 | ||
| Prolonging the action of local anesthetics | 649 | ||
| Acute hypersensitivity reactions | 649 | ||
| Adverse effects | 649 | ||
| Cardiac effects | 649 | ||
| CNS effects | 649 | ||
| Endocrinologic effects | 649 | ||
| Local ischemia | 649 | ||
| Drug interactions | 650 | ||
| β-Blockers | 650 | ||
| Tricyclic antidepressants | 650 | ||
| Other medications | 650 | ||
| Therapeutic guidelines | 650 | ||
| Other agents with local anesthetic effects | 650 | ||
| Capsaicin | 650 | ||
| Clinical use | 650 | ||
| FDA-approved dermatologic indications | 650 | ||
| Postherpetic neuralgia | 650 | ||
| Off-label dermatologic uses | 651 | ||
| Adverse effects | 651 | ||
| Drug interactions | 651 | ||
| Therapeutic guidelines | 651 | ||
| Diphenhydramine | 651 | ||
| Bibliography: important reviews and chapters | 652 | ||
| Local anesthesia | 652 | ||
| Topical anesthesia | 652 | ||
| References* | 652 | ||
| Web references | 652.e1 | ||
| Lidocaine – pharmacology | 652.e1 | ||
| Lidocaine – clinical use | 652.e1 | ||
| Lidocaine – adverse effects | 652.e1 | ||
| Lidocaine – drug interactions and therapeutic guidelines | 652.e2 | ||
| Eutectic mixture of local anesthesia (EMLA) – pharmacology | 652.e2 | ||
| EMLA – clinical use | 652.e2 | ||
| EMLA – adverse effects | 652.e2 | ||
| Topical anesthetics – lidocaine, benzocaine, dyclonine | 652.e2 | ||
| Epinephrine – pharmacology and clinical use | 652.e2 | ||
| Epinephrine – adverse effects | 652.e3 | ||
| Epinephrine – drug interactions and therapeutic guidelines | 652.e3 | ||
| Capsaicin – clinical use | 652.e3 | ||
| Antihistamines – diphenhydramine, doxepin | 652.e3 | ||
| 57 Injectable dermal and subcutaneous fillers | 653 | ||
| Introduction | 653 | ||
| Categories of dermal fillers | 653 | ||
| Collagen | 653 | ||
| Hyaluronic acid | 653 | ||
| Calcium hydroxyapatite | 655 | ||
| Poly-l-lactic acid | 655 | ||
| Polymethylmethacrylate | 655 | ||
| Silicone | 655 | ||
| Fillers on the horizon | 656 | ||
| Adverse effects (Box 57-2) | 656 | ||
| Immediate adverse effects (0–2 days) | 656 | ||
| Early adverse effects (3–14 days) | 656 | ||
| Late adverse effects (15 days to 1 year) | 656 | ||
| Delayed (>1 year) | 657 | ||
| Bibliography: important reviews and chapters | 657 | ||
| Web references | 657.e1 | ||
| References* | 657 | ||
| 58 Botulinum toxin injections | 658 | ||
| Introduction and history | 658 | ||
| Pharmacology | 658 | ||
| Structure and serotypes | 658 | ||
| Physiology of nerves | 659 | ||
| Mechanism of action | 659 | ||
| Inhibition of neuromuscular function | 659 | ||
| Recovery of neuromuscular function | 659 | ||
| Determination of botulinum activity | 659 | ||
| Botulinum a toxin product details | 660 | ||
| Clinical use | 661 | ||
| Patient evaluation | 661 | ||
| Indications | 662 | ||
| Overview of potential indications | 662 | ||
| Facial rhytides | 662 | ||
| Hyperhidrosis | 663 | ||
| Contraindications | 663 | ||
| Adverse effects | 663 | ||
| General effects | 663 | ||
| Antibodies to botulinum toxin | 663 | ||
| Adverse effects related to injection technique | 664 | ||
| Therapeutic guidelines | 664 | ||
| Injection technique – general aspects | 664 | ||
| Forehead injections | 664 | ||
| Glabella injections | 664 | ||
| Lateral canthus injections | 664 | ||
| Neck injections | 665 | ||
| Hyperhidrosis | 665 | ||
| Follow-up | 665 | ||
| Conclusions | 665 | ||
| Bibliography: important reviews and chapters | 665 | ||
| Web references | 665.e1 | ||
| Introduction & pharmacology | 665.e1 | ||
| Clinical use – patient evaluation | 665.e1 | ||
| Clinical use – indications | 665.e1 | ||
| Contraindications and adverse effects | 665.e1 | ||
| Therapeutic guidelines (see also ref. 10). | 665.e1 | ||
| References* | 665 | ||
| 59 Oral mucosal therapeutics | 666 | ||
| Introduction | 666 | ||
| Review of common terminology | 666 | ||
| Erosive gingivostomatitis | 666 | ||
| Tips and clinical pearls – erosive gingivostomatitis | 667 | ||
| Mouth rinses | 667 | ||
| Topical therapy | 668 | ||
| Corticosteroids | 668 | ||
| Steroid-sparing immunosuppressants | 668 | ||
| Topical anesthetics | 669 | ||
| Intralesional corticosteroids | 669 | ||
| XII Major Adverse Effects from Systemic Drugs | 677 | ||
| 60 Hepatotoxicity of dermatologic drug therapy | 677 | ||
| Introduction | 677 | ||
| The liver and drug metabolism | 677 | ||
| Hepatic drug metabolism | 677 | ||
| Polymorphisms | 678 | ||
| Mechanisms of drug hepatotoxicity | 679 | ||
| General mechanisms involved | 679 | ||
| Toxic versus idiosyncratic reactions | 680 | ||
| Risk factors for drug hepatotoxicity | 681 | ||
| General risk factors | 681 | ||
| Drug-specific risk factors | 681 | ||
| Predictive testing for polymorphisms | 682 | ||
| Drug information dissemination issues | 682 | ||
| Limits of clinical trials in predicting hepatotoxicity | 682 | ||
| Risk with real world drug use | 682 | ||
| Potential predictors of hepatotoxicity | 682 | ||
| Importance of disseminating of drug safety information | 682 | ||
| Classification systems (Table 60-7) | 683 | ||
| Drug etiologies | 684 | ||
| Common dermatologic drug etiologies | 684 | ||
| Less common drug etiologies | 684 | ||
| Diagnosis | 684 | ||
| Diagnostic algorithm | 684 | ||
| Differential diagnosis | 685 | ||
| Referral criteria | 685 | ||
| Liver ‘function’ tests | 685 | ||
| Management | 686 | ||
| Background issues | 686 | ||
| Management options | 686 | ||
| Looking to the future – lessons from the past | 687 | ||
| Bibliography: important reviews and chapters | 688 | ||
| General overviews | 688 | ||
| General mechanisms of hepatotoxicity | 688 | ||
| Liver ‘function’ tests | 688 | ||
| Psoriasis and methotrexate-induced liver disease | 688 | ||
| References* | 689 | ||
| Web references | 689.e1 | ||
| Introduction | 689.e1 | ||
| The liver and drug metabolism | 689.e1 | ||
| Mechanisms of drug hepatotoxicity | 689.e1 | ||
| Risk factors for drug hepatotoxicity | 689.e1 | ||
| Drug information dissemination/ drug withdrawal | 689.e1 | ||
| Causality assessment | 689.e1 | ||
| Liver ‘function’ tests | 689.e2 | ||
| 61 Hematologic toxicity of drug therapy | 690 | ||
| Introduction | 690 | ||
| General principles | 690 | ||
| Mechanisms of hematologic toxicities | 690 | ||
| Timing of hematologic toxicity | 691 | ||
| Prediction of risk for hematologic toxicities | 691 | ||
| Major categories of drug-induced hematologic toxicity | 691 | ||
| Agranulocytosis | 691 | ||
| Aplastic anemia (pancytopenia) | 692 | ||
| Thrombocytopenia | 692 | ||
| Neoplasia | 693 | ||
| Drugs Prescribed by Dermatologists – Risk of Hematologic Toxicity | 693 | ||
| Methotrexate | 693 | ||
| Mechanism of toxicity | 693 | ||
| General risk of hematologic toxicity | 694 | ||
| XIII Special Pharmacology and Therapeutic Topics | 757 | ||
| 67 Pharmacoeconomics | 757 | ||
| Introduction | 757 | ||
| Various cost analyses | 757 | ||
| Cost-minimization analysis Q67-1 | 757 | ||
| Cost–benefit analysis | 757 | ||
| Cost-effectiveness analysis | 758 | ||
| Cost–utility analysis | 758 | ||
| ‘Forgotten’ and indirect costs of therapy | 759 | ||
| Analyzing the various cost analyses | 759 | ||
| Comparison of four primary cost analysis methods | 759 | ||
| General principles for using these cost analysis methods | 759 | ||
| Areas of controversy | 760 | ||
| How are pharmacoeconomic analyses used? | 760 | ||
| Formulary decisions | 760 | ||
| ‘Negotiations’ with patients and insurers | 761 | ||
| Evaluating pharmaceutical company trials | 761 | ||
| Current trends in drug prices | 762 | ||
| Physician role in drug cost control | 763 | ||
| Pharmaceutical pricing strategies | 763 | ||
| Three basic pricing strategies | 763 | ||
| Average wholesale price | 763 | ||
| Wholesale acquisition cost | 763 | ||
| Pharmaceutical manufacturer costs | 763 | ||
| Pharmaceutical patient assistance programs | 763 | ||
| Generic drugs and substitution | 764 | ||
| Why is pharmacoeconomics important to clinicians? | 764 | ||
| Bibliography: important reviews and chapters | 764 | ||
| References* | 764 | ||
| Web References | 765.e1 | ||
| Introduction | 765.e1 | ||
| Cost analysis methods | 765.e1 | ||
| Assessing the various cost analysis methods | 765.e1 | ||
| How are pharmaceutical cost analyses used | 765.e1 | ||
| Pharmaceutical company pricing strategies | 765.e1 | ||
| 68 Informed consent and risk management | 766 | ||
| Introduction | 766 | ||
| Historical perspective | 766 | ||
| Ethical perspective | 766 | ||
| Basic legal principles | 767 | ||
| Components of informed consent | 768 | ||
| Systemic drugs and informed consent | 768 | ||
| Optimizing patient understanding | 769 | ||
| Exceptions to the informed consent requirements | 769 | ||
| Medicolegal risk management | 769 | ||
| Appendix I – Ten drugs of increasing importance to dermatology | 787 | ||
| Newer drugs | 787 | ||
| Older drugs | 787 | ||
| Newer melanoma chemotherapy drugs covered elsewhere in the book | 787 | ||
| Bibliography – BELIMUMAB | 787 | ||
| Bibliography – CANAKINUMAB | 788 | ||
| Bibliography – ICATIBANT | 788 | ||
| Bibliography – INGENOL MEBUTATE | 789 | ||
| Bibliography – VISMODEGIB | 789 | ||
| Bibliography – BIMATOPROST | 790 | ||
| Bibliography – OMALIZUMAB | 790 | ||
| Bibliography – OXYBUTYNIN | 791 | ||
| Appendix II – Dapsone patient education and informed consent | 792 | ||
| Disease being treated with dapsone | 792 | ||
| Boxed warnings – most serious risks from the drug | 792 | ||
| Contraindications – reasons you can possibly not take this drug | 792 | ||
| Dapsone use in pregnancy | 792 | ||
| Possible drug interactions | 792 | ||
| Most important side effects – report these findings to doctor right away | 792 | ||
| Common side effects – of less concern | 792 | ||
| Rare, but important to report to doctor | 792 | ||
| Laboratory testing | 792 | ||
| Subject Index | 793 | ||
| A | 793 | ||
| B | 797 | ||
| C | 798 | ||
| D | 802 | ||
| E | 805 | ||
| F | 806 | ||
| G | 807 | ||
| H | 807 | ||
| I | 809 | ||
| J | 811 | ||
| K | 811 | ||
| L | 811 | ||
| M | 813 | ||
| N | 814 | ||
| O | 815 | ||
| P | 816 | ||
| Q | 820 | ||
| R | 820 | ||
| S | 821 | ||
| T | 823 | ||
| U | 825 | ||
| V | 825 | ||
| W | 826 | ||
| X | 826 | ||
| Z | 826 |