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Author, subject index and contents to volume 40
PHARMACOLOGY & THERAPEUTICS Volume 40
Executive Editors
W. C. Bowman, A. M. Breckenridge and A. C. Sartorelli
PERGAMON
OXFORD
• NEW
S/~O PAULO
YORK
• SYDNEY
PRESS
• BEIJING • TOKYO
• FRANKFURT • TORONTO
PHARMACOLOGY & THERAPEUTICS Chemotherapy, Toxicology and Metabolic lnhibitors Executive Editor: A. C. Sartorelli Yale University School of Medicine, Department of Pharmacology, 333 Cedar Street, New Haven, Connecticut 06510, USA
Associate Editor: Barbara Z. Renkin, Ph.D. General and Systemic Pharmacology Executive Editor: W. C. Bowman University of Strathclyde, Department of Physiology & Pharmacology, Royal College, 204 George Street, Glasgow G I 1XW, Scotland
Clinical Pharmacology and Therapeutics Executive Editor: A. M. Breckenridge University of Liverpool, Department of Pharmacology & Therapeutics, P.O. Box 147, Liverpool L69 3BX, England Library Annual Subscription Rates--published in 4 volumes per annum of 3 issues each. Annual Subscription, 1989, DM 2150.00 including postage and insurance, 2 years, 1989/90, DM 4085.00. Specially Reduced Rates to Individuals: Any individual whose institution takes out a library subscription may purchase a second or additional subscription for personal use at a much reduced rate of DM 740.00 annually. Subscribers to the Journal may claim a 20% discount off Encyclopedia volumes. Prices are subject to change without notice. Subscription enquiries from customers in North America should be sent to Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523, USA, and for the remainder of the world to Pergamon Press pie, Headington Hill Hall, Oxford OX3 0BW, England. At the end of the year, the Subscriber will receive, free, the annual subject index. It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that the copyright for their article is transferred to the publisher if and when the article is accepted for publication. However, assignment of copyright is not required from authors who work for organisations which do not permit such assignment. The copyright covers the exclusive rights to reproduce and distribute the article, including reprints, photographic reproduction, microform or any other reproduction of similar nature and translations. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical photocopying recording or otherwise, without permission in writing from the copyright holder.
Photocopying Information for Users in the USA. The Item-Fee Code for this publication indicates that authorization to photocopy items for internal or personal use is granted by the copyright holder for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service provided the stated fee for copying, beyond that permitted by Section 107 or 108 of the United States Copyright Law, is paid. The appropriate remittance of $0.50 per page is paid directly to the Copyright Clearance Center Inc., 27 Congress Street, Salem, MA 01970. Permission for other Use. The copyright owner's consent does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific written permission must be obtained from the publisher for such copying. Microform Subscriptions and Back Issues Back issues of all previously published volumes are available direct from Pergamon Press. Back issues of Pergamon journals in microform can be obtained from UMI. 300 North Zeeb Road, Ann Arbor, Michigan 48106, USA. Publishing and Advertising Offices Pergamon Press plc Headington Hill Hall Oxford OX3 0BW England
Pergamon Press Inc. Maxwell House Fairview Park, Elmsford New York 10523, USA
Volume 40, 1989, Numbers 1-3 CONTENTS
Number 1
PAGE
The pharmacology and pharmacokinetics of the retinoids: J. G. Allen and D. P. Bloxham Retinoids: Toxicology and teratogenicity to date: K. Teelman Retinoid binding proteins and human skin: G. Siegenthaler and J.-H. Saurat Lipid metabolism and retinoid therapy: J. R. Marsden Results of therapy for psoriasis using retinoid and photochemotherapy (RePuva): H. Hiinigsmann and K. Wolff Darier's disease and other dyskeratoses: response to retinoids: S. M. Burge The role and mechanism of action of 13-cis-retinoic acid in the treatment of severe (nodulocystic) acne: D. H. Jones Results of the use of vitamin A and retinoids in cutaneous malignancies: S. M. Lippman and F. L. Meyskens, Jr Retinoid associated phototoxicity and photosensitivity: J. Ferguson and B. E. Johnson Bone changes associated with oral retinoid therapy: S. 1. White and R. M. Mackie Liver toxicity of retinoid therapy: H. H. Roenigk, Jr Newer retinoids for psoriasis--early clinical studies: L. Matt, V. N. Lazarus and N. J. Lowe
1
29 45 55 67 75 91 107 123 137 145 157
Number 2
Preface Modification of membrane permeability by animal viruses: L. Carrasco, M. J. Otero and J. L. Castrillo Antiviral effects of phosphonoformate (PFA, foscarnet sodium): B. (~berg Rapid and accurate viral diagnosis: M. L. Landry, D. R. Mayo and G. D. Hsiung
vii 171 213 287
Number 3
Anti-retroviral therapy of AIDS and related disorders: general principles and specific development of dideoxynucleosides: R. Yarchoan and S. Broder Enhancement of 5-fluorouracil's anticancer activity by dipyridamole: J. L. Grem and P. H. Fisher Platelet activating factor and airway smooth muscle: J. Morley, D. Smith and 1. Chapman The development of hypoxic tumor cell cytotoxic agents: D. L. Kirkpatrick Novel autonomic neurotransmitters and intestinal function: G. S. Taylor and R. A. R. Bywater Drug metabolism in liver disease: C. IV. Howden, G. G. Birnie and M. J. Brodie
iii
329 349 373 383 401 439
AUTHOR INDEX Landry, M . L . 287 Lazarus, V . N . 157 Lippman, S.M. 107 Lowe, N . J . 157
Allen, J. G. 1 Birnie, G . G . 439 Bloxham, D . P . 1 Broder, S. 329 Brodie, M . J . 439 Burge, S.M. 75 Bywater, R. A. R. 401
MacKie, R . M . 137 Marsden, J . R . 55 Matt, L. 157 Mayo, D . R . 287 Meyskens, F. L., Jr 107 Morley, J. 373
Carrasco, L. 171 Castrillo, J . L . 171 Chapman, I 373
Ferguson, J. Fisher, P . H .
123 349
Grem, J . L .
349
Oberg, B. 213 Otero, M . J . 171 Roenigk, H. H., Jr Saurat, J.-H. 45 Siegenthaler, G 45 Smith, D. 373
HOnigsmann, H. 67 Howden, C . W . 439 Hsiung, G . D . 287
Taylor, G . S . 401 Teelmann, K. 29
Johnson, B . E . 123 Jones, D . H . 91
Kirkpatrick, D . L .
White, S.I. 137 Wolff, K. 67 Yarchoan, R.
383
iv
329
145
SUBJECT INDEX Acyclovir 311 Adenine arabinoside 310 Adenosine triphosphate 406, 407 Acitretin pharmacokinetics 159~1 structure 17 Acne appearance 92, 93 13-c/s-retinoic acid 91-104, 129 clinical efficacy 92-95 erythromycin 97, 98 pilosebaceous duct obstruction 101, 102 remission rates 95, 96 sebum excretion and retinoids 98-100 skin microflora 100, 101 Adverse reactions AZT 339 phosphonoformate 240-42, 258, 259 RePUVA 70, 71 retinoids 87 synthetic retinoids 165, 166 AIDS anti-retroviral therapy 329-44 approaches 330-33 CMV infection and phosphonoformate 269-72 Airway smooth muscle hyperactivity 375-377, 379 platelet activating factor 373--80 Amantadine 309 "v-Aminobutyric acid (GABA) 407-409 Antipyrine clearance and cirrhosis 467 Antiviral drugs 309-13 sensitivity testing 313,314 Arotinoid ethyl ester 161, 162 AZT clinical activity in AIDS 338-43 HIV-induced neurologic dysfunction 341,342 structure 334 toxicity 339
Bioavailability 441 Bone retinoid therapy 137-42 retinoid toxicity 35, 36
Calcitonin gene-related peptide 409, 410 Carcinogenesis, retinoids 40 Cellular retinoic acid-binding protein (CRABP) skin assay 48-50 skin disease 51, 52 Cholecystokinin 410 Cirrhosis drug metabolism 447-49, 460, 462 midazolam, plasma concentration 449 Clearance 442, 443 intrinsic 443,444 Cytopathic effects, virus 292 Cytotoxic agents, hypoxic tumour cell 383-96
Darier's disease appearance 78-80 retinoid effects 81 Dideoxynucleosides 329-46 anabolic phosphorylation 337, 338 analogues 333-36 HIV activity 334, 335 mechanisms of action 336 structures 334 types 343, 344 Dipyridamole and antimetabolite toxicity 360-62 antineoplastic agent modulator 364, 365 cancer cell heterogeneity 366 5-fluorouracil anticancer enhancement 349-67 pharmacology in man 363 platelet antiaggregation 362 Drug metabolism dose and liver disease 450-59 in vitro 463-65 in vitro 446, 447 liver disease 439-69 parameters in liver disease 450-59 protein binding 444, 445
ELISA, viral antigens 304, 305 Enteric nervous system 401 peptides 402 Epidermal differentiation 75, 76 Epidermis, retinoid effects 34, 77, 78 Etretinate absorption spectrum 128 bone effects 140-42 clinical studies 128, 129, 159, 160 concentration-time profiles 18 dosimetry 160 lipid metabolism 59, 60 liver effects 151-53 metabolism 20 metabolites 17 minimal erythema dose 130 pharmacokinetics 17-22, 159 PUVA combination 162, 163 structure 17 therapeutic index 16 UVB combination 163, 164
5-Fluorouracil (5-FU) anticancer and dipyridamole 349-68 dipyridamole interaction 350 cell growth 352,353 metabolism 356 metabolite efflux 356, 357 nucleoside transport 353-55 toxicity modulation 358 Foscamet see phosphonoformate
vi
SUBJECT INDEX
Galanin 411 Gastrin-releasing peptide 411,412 Gilbert's syndrome, drug metabolism
462, 463
Hepatitis, drug, metabolism 461,462 5-Hydroxytryptamine 412,413 Hyperlipidaemia, mechanisms of retinoid 60--62 management 63 Hypervitaminosis A 145, 146 Ichthyosis features of congenital 82, 83 retinoid, actions 86, 87 X-linked 85 Immunofluorescene, viral antigen 301,302 Immunoperoxidase, viral antigen 320-304 Iododeoxyuridine 309-16 Jaundice, drug metabolism Keratinization disorders
462
83--85
Lipid metabolism normal 55 and retinoid therapy 55-63 Lipoproteins metabolism, scheme 57 normal, features 56 Liver biopsy, retinoid therapy 148-152 retinoid metabolism 146 retinoid toxicity 37, 38 toxicity, vitamin A 145-53 Liver disease classification 440 diagnosis 439 drug pharmacokinetics 450-59 modeling 445 pathology 440 shunting 445 Liver function tests aminopyrine 467,468 antipyrine 466, 467 indocyanine green 465,466 Melanoma, retinoids 115, 116 Membrane leakiness molecule entry 178-81 molecule exit 181, 182 transport modification 182 virus infection 177-89 early 177-82 late 182-89 Membrane modifications cell killing 92 cell metabolism 189-91 cell transformation 193, 194 RNA synthesis 191, 192 and virus infection 189-96 Membrane permeability agents 196-203 ATP 202 ionic concentrations 199-201 ionophores 197-99 lysolethicin 201
measurement 178, 179 picornavirus 184-86 thionins 203 togaviruses 186, 187 viral entry 194, 195 viral macromolecules 195, 196 viral types and effects 183 virus infection 171-204 DNA 188, 189 modification 172 RNA 184-88 Meptazinol in liver disease 460 Misonidazole 392 Monensin structure 198 Mutagenesis and retinoids 40 Mycosis fungoides, retinoids 116-18
Neurokinins 413-15 Neuropeptide Y 415-17 Neurotensin 417,418 Neurotransmitters, autonomic 401-26 novel 405-26 putative 406 release 403,404 Nigericin structures 198 Nitroimidazole analogues 391-96 structure 392-95 Nucleosides, membrane transport 351,352
Opioid peptides
418-20
Peptide histidine isoleucine 422-26 Pharmacokinetics in liver disease 441--46 Phosphonoformate animal treatment 242-52 efficiency 244-49 antiviral effects 277 cellular toxicity 240-42 chemistry 215,216 clinical studies 259-76 CMV infection 265-69 AIDS patients 269-72 bone marrow transplant 265, 268 clinical effects 266 renal transplants 265, 267 CMV sensitivity 227 CMV synthesis 225 DNAase 220 DNA polymerase 219, 220 inhibition model 234, 235 interactions 236 drug combinations 252-55 HIV replication 255 enzymes inhibited 216-24 structure-activity 220-24 fibroblast uptake 241,242 half-life, blood 256 hepatitis B virus infection 272,274 herpes, cutaneous in animals 243-49 herpes, genital in animals 249,250 herpes, genital, clinical studies 260~5 herpes, keratitis 250, 251 herpes, labial, clinical studies 259, 260 herpes, viral excretion 263 HIV infection 272, 273 HIV isolation 273 HIV replication 228, 229, 236,237
SUBJECT INDEX HSV-1 238,239 mechanisms of action 230-40 cell cultures 237--40 cell-free system 230-37 mechanism of inhibition 232, 233 parenteral, safety 275,276 pharmacokinetics 255-58 plasma clearance 257 polymerase activities 222 resistance 252, 253 reverse transcriptions 218, 219 time course 236, 237 RNAase 220 RNA polymerases 217,218 structure 215 toxicology 258, 259 virus multiplication 224-29 cell culture 226 Photohaemolysis, UVA and retinoids 131, 132 Photosensitivity drug-induced 123 retinoid-induced 127, 128 Photosensitization 123 drugs 125 mechanisms 125-27 retinoids 124 Photosensitizers 124, 125 Phototoxicity, cutaneous 127 Platelet activating factor and airway smooth muscle 373-80 bronchospasm 374, 375,378 cough 378 vascular permeability 377, 378 Protein kinase C, retinoid modulation 107 Psoriasis therapy 67-72 see also RePUVA new retinoids 157-66 retinoid actions 157 Psoriatic arthritis, retinoids 164, 165 Pyrimidine synthesis, salvage pathways 350, 351 Pyrophosphate analogues, polymerase inhibition 222, 223
Quinone bioreductive alkylating agents 383-91 mitomycin C 389 structures 384--86,388-91
Radioimmunoassay (RIA), viral antigen 306 RePUVA (retinoid and photochemotherapy) 67-72 mechanisms of action 71 principles 67, 68 protocols 68-70 psoriasis 162, 163 results 68, 69 side effects 70, 71 Resistance, phosphonoformate 252, 253 Retinaldehyde 3--6 Retinoic acid, all-trans- 6--9 mechanism of action 13-16 metabolism, scheme 7 pharmacokinetics 8, 9 utriculus diameter 14 Retinoic acid, c/s (isotretinoin) 9-13 acne 91-104 blood levels 11, 13 bone effects 139, 140 lipid metabolism 58, 59 mechanism of action 13-16
metabolism 12 utriculus diameter 14 Retinoid-binding proteins 45-53 see also cellular retinoic acid binding binding affinities 50 oral mucosa 48, 49 PAGE assay 48 skin 47-49 Retinoids biological efficacy 22 carriers 45-53 cutaneous malignancies 107-19 mechanism of action 29, 31 new, synthetic 158 pharmacology 1-23 photosensitivity 123-33 skin neoplasia 114 skin preneoplasia 110-13 structures 30, 46 target organ toxicity 32-38 therapy and lipid metabolism 55--63 third generation 22, 23 tolerance and dose 31, 32 toxicology 29--40 Retinol 1-3 formula 2 Ribavirin 311
Skeletal hyperostosis 138, 139 Skin carcinogenesis 108, 109 microflora and ache therapy 100, 101 retinoid toxicity 34, 77, 78 Skin cancer basal cell 113 preneoplasia and retinoids 110-13 prevention 109 squamous cell 113 Somatostatin 420-22 Specimen collection and transport, virus 289, 290
Teratogenesis, retinoids 38--40 Toxicity retinoids 29--40 synthetic retinoids 165, 166 Trifiuorothymidine 310
Vasoactive intestinal polypeptide 422-26 Viral diagnosis antigen detection 301-306 cytopathic effects 292, 293 importance 314-16 methods 287-316 rapid 300-309 specimens and disease 289 Viral genome detection 306-9 Virus cell entry modes 173-77 cytopathic effects 193 endocytosis 174 HIV replication stages 331 and membrane permeability 171-204 Virus identification microscopy 298 monoclonal antibodies 295 restriction endonuclease 297, 298 RNA genome analysis 296
vii
viii Virus-induced cellular changes 290, 291 Virus isolation 290-92 cultivation 294, 295 HIV 295 specimen processing 293 Virus multiplication, phosphonoformate 224-29 Virus shapes, RNA and DNA 298-300
SUBJECT INDEX Vitamin A anticancer effects 107 and bone 137, 138 liver storage 145, 146 liver toxicity 145-53 metabolism scheme 4 skin cancer 109
Executive Editors
W. C. Bowman, A. M. Breckenridge and A. C. Sartorelli
PERGAMON
OXFORD
• NEW
S/~O PAULO
YORK
• SYDNEY
PRESS
• BEIJING • TOKYO
• FRANKFURT • TORONTO
PHARMACOLOGY & THERAPEUTICS Chemotherapy, Toxicology and Metabolic lnhibitors Executive Editor: A. C. Sartorelli Yale University School of Medicine, Department of Pharmacology, 333 Cedar Street, New Haven, Connecticut 06510, USA
Associate Editor: Barbara Z. Renkin, Ph.D. General and Systemic Pharmacology Executive Editor: W. C. Bowman University of Strathclyde, Department of Physiology & Pharmacology, Royal College, 204 George Street, Glasgow G I 1XW, Scotland
Clinical Pharmacology and Therapeutics Executive Editor: A. M. Breckenridge University of Liverpool, Department of Pharmacology & Therapeutics, P.O. Box 147, Liverpool L69 3BX, England Library Annual Subscription Rates--published in 4 volumes per annum of 3 issues each. Annual Subscription, 1989, DM 2150.00 including postage and insurance, 2 years, 1989/90, DM 4085.00. Specially Reduced Rates to Individuals: Any individual whose institution takes out a library subscription may purchase a second or additional subscription for personal use at a much reduced rate of DM 740.00 annually. Subscribers to the Journal may claim a 20% discount off Encyclopedia volumes. Prices are subject to change without notice. Subscription enquiries from customers in North America should be sent to Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523, USA, and for the remainder of the world to Pergamon Press pie, Headington Hill Hall, Oxford OX3 0BW, England. At the end of the year, the Subscriber will receive, free, the annual subject index. It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that the copyright for their article is transferred to the publisher if and when the article is accepted for publication. However, assignment of copyright is not required from authors who work for organisations which do not permit such assignment. The copyright covers the exclusive rights to reproduce and distribute the article, including reprints, photographic reproduction, microform or any other reproduction of similar nature and translations. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical photocopying recording or otherwise, without permission in writing from the copyright holder.
Photocopying Information for Users in the USA. The Item-Fee Code for this publication indicates that authorization to photocopy items for internal or personal use is granted by the copyright holder for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service provided the stated fee for copying, beyond that permitted by Section 107 or 108 of the United States Copyright Law, is paid. The appropriate remittance of $0.50 per page is paid directly to the Copyright Clearance Center Inc., 27 Congress Street, Salem, MA 01970. Permission for other Use. The copyright owner's consent does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific written permission must be obtained from the publisher for such copying. Microform Subscriptions and Back Issues Back issues of all previously published volumes are available direct from Pergamon Press. Back issues of Pergamon journals in microform can be obtained from UMI. 300 North Zeeb Road, Ann Arbor, Michigan 48106, USA. Publishing and Advertising Offices Pergamon Press plc Headington Hill Hall Oxford OX3 0BW England
Pergamon Press Inc. Maxwell House Fairview Park, Elmsford New York 10523, USA
Volume 40, 1989, Numbers 1-3 CONTENTS
Number 1
PAGE
The pharmacology and pharmacokinetics of the retinoids: J. G. Allen and D. P. Bloxham Retinoids: Toxicology and teratogenicity to date: K. Teelman Retinoid binding proteins and human skin: G. Siegenthaler and J.-H. Saurat Lipid metabolism and retinoid therapy: J. R. Marsden Results of therapy for psoriasis using retinoid and photochemotherapy (RePuva): H. Hiinigsmann and K. Wolff Darier's disease and other dyskeratoses: response to retinoids: S. M. Burge The role and mechanism of action of 13-cis-retinoic acid in the treatment of severe (nodulocystic) acne: D. H. Jones Results of the use of vitamin A and retinoids in cutaneous malignancies: S. M. Lippman and F. L. Meyskens, Jr Retinoid associated phototoxicity and photosensitivity: J. Ferguson and B. E. Johnson Bone changes associated with oral retinoid therapy: S. 1. White and R. M. Mackie Liver toxicity of retinoid therapy: H. H. Roenigk, Jr Newer retinoids for psoriasis--early clinical studies: L. Matt, V. N. Lazarus and N. J. Lowe
1
29 45 55 67 75 91 107 123 137 145 157
Number 2
Preface Modification of membrane permeability by animal viruses: L. Carrasco, M. J. Otero and J. L. Castrillo Antiviral effects of phosphonoformate (PFA, foscarnet sodium): B. (~berg Rapid and accurate viral diagnosis: M. L. Landry, D. R. Mayo and G. D. Hsiung
vii 171 213 287
Number 3
Anti-retroviral therapy of AIDS and related disorders: general principles and specific development of dideoxynucleosides: R. Yarchoan and S. Broder Enhancement of 5-fluorouracil's anticancer activity by dipyridamole: J. L. Grem and P. H. Fisher Platelet activating factor and airway smooth muscle: J. Morley, D. Smith and 1. Chapman The development of hypoxic tumor cell cytotoxic agents: D. L. Kirkpatrick Novel autonomic neurotransmitters and intestinal function: G. S. Taylor and R. A. R. Bywater Drug metabolism in liver disease: C. IV. Howden, G. G. Birnie and M. J. Brodie
iii
329 349 373 383 401 439
AUTHOR INDEX Landry, M . L . 287 Lazarus, V . N . 157 Lippman, S.M. 107 Lowe, N . J . 157
Allen, J. G. 1 Birnie, G . G . 439 Bloxham, D . P . 1 Broder, S. 329 Brodie, M . J . 439 Burge, S.M. 75 Bywater, R. A. R. 401
MacKie, R . M . 137 Marsden, J . R . 55 Matt, L. 157 Mayo, D . R . 287 Meyskens, F. L., Jr 107 Morley, J. 373
Carrasco, L. 171 Castrillo, J . L . 171 Chapman, I 373
Ferguson, J. Fisher, P . H .
123 349
Grem, J . L .
349
Oberg, B. 213 Otero, M . J . 171 Roenigk, H. H., Jr Saurat, J.-H. 45 Siegenthaler, G 45 Smith, D. 373
HOnigsmann, H. 67 Howden, C . W . 439 Hsiung, G . D . 287
Taylor, G . S . 401 Teelmann, K. 29
Johnson, B . E . 123 Jones, D . H . 91
Kirkpatrick, D . L .
White, S.I. 137 Wolff, K. 67 Yarchoan, R.
383
iv
329
145
SUBJECT INDEX Acyclovir 311 Adenine arabinoside 310 Adenosine triphosphate 406, 407 Acitretin pharmacokinetics 159~1 structure 17 Acne appearance 92, 93 13-c/s-retinoic acid 91-104, 129 clinical efficacy 92-95 erythromycin 97, 98 pilosebaceous duct obstruction 101, 102 remission rates 95, 96 sebum excretion and retinoids 98-100 skin microflora 100, 101 Adverse reactions AZT 339 phosphonoformate 240-42, 258, 259 RePUVA 70, 71 retinoids 87 synthetic retinoids 165, 166 AIDS anti-retroviral therapy 329-44 approaches 330-33 CMV infection and phosphonoformate 269-72 Airway smooth muscle hyperactivity 375-377, 379 platelet activating factor 373--80 Amantadine 309 "v-Aminobutyric acid (GABA) 407-409 Antipyrine clearance and cirrhosis 467 Antiviral drugs 309-13 sensitivity testing 313,314 Arotinoid ethyl ester 161, 162 AZT clinical activity in AIDS 338-43 HIV-induced neurologic dysfunction 341,342 structure 334 toxicity 339
Bioavailability 441 Bone retinoid therapy 137-42 retinoid toxicity 35, 36
Calcitonin gene-related peptide 409, 410 Carcinogenesis, retinoids 40 Cellular retinoic acid-binding protein (CRABP) skin assay 48-50 skin disease 51, 52 Cholecystokinin 410 Cirrhosis drug metabolism 447-49, 460, 462 midazolam, plasma concentration 449 Clearance 442, 443 intrinsic 443,444 Cytopathic effects, virus 292 Cytotoxic agents, hypoxic tumour cell 383-96
Darier's disease appearance 78-80 retinoid effects 81 Dideoxynucleosides 329-46 anabolic phosphorylation 337, 338 analogues 333-36 HIV activity 334, 335 mechanisms of action 336 structures 334 types 343, 344 Dipyridamole and antimetabolite toxicity 360-62 antineoplastic agent modulator 364, 365 cancer cell heterogeneity 366 5-fluorouracil anticancer enhancement 349-67 pharmacology in man 363 platelet antiaggregation 362 Drug metabolism dose and liver disease 450-59 in vitro 463-65 in vitro 446, 447 liver disease 439-69 parameters in liver disease 450-59 protein binding 444, 445
ELISA, viral antigens 304, 305 Enteric nervous system 401 peptides 402 Epidermal differentiation 75, 76 Epidermis, retinoid effects 34, 77, 78 Etretinate absorption spectrum 128 bone effects 140-42 clinical studies 128, 129, 159, 160 concentration-time profiles 18 dosimetry 160 lipid metabolism 59, 60 liver effects 151-53 metabolism 20 metabolites 17 minimal erythema dose 130 pharmacokinetics 17-22, 159 PUVA combination 162, 163 structure 17 therapeutic index 16 UVB combination 163, 164
5-Fluorouracil (5-FU) anticancer and dipyridamole 349-68 dipyridamole interaction 350 cell growth 352,353 metabolism 356 metabolite efflux 356, 357 nucleoside transport 353-55 toxicity modulation 358 Foscamet see phosphonoformate
vi
SUBJECT INDEX
Galanin 411 Gastrin-releasing peptide 411,412 Gilbert's syndrome, drug metabolism
462, 463
Hepatitis, drug, metabolism 461,462 5-Hydroxytryptamine 412,413 Hyperlipidaemia, mechanisms of retinoid 60--62 management 63 Hypervitaminosis A 145, 146 Ichthyosis features of congenital 82, 83 retinoid, actions 86, 87 X-linked 85 Immunofluorescene, viral antigen 301,302 Immunoperoxidase, viral antigen 320-304 Iododeoxyuridine 309-16 Jaundice, drug metabolism Keratinization disorders
462
83--85
Lipid metabolism normal 55 and retinoid therapy 55-63 Lipoproteins metabolism, scheme 57 normal, features 56 Liver biopsy, retinoid therapy 148-152 retinoid metabolism 146 retinoid toxicity 37, 38 toxicity, vitamin A 145-53 Liver disease classification 440 diagnosis 439 drug pharmacokinetics 450-59 modeling 445 pathology 440 shunting 445 Liver function tests aminopyrine 467,468 antipyrine 466, 467 indocyanine green 465,466 Melanoma, retinoids 115, 116 Membrane leakiness molecule entry 178-81 molecule exit 181, 182 transport modification 182 virus infection 177-89 early 177-82 late 182-89 Membrane modifications cell killing 92 cell metabolism 189-91 cell transformation 193, 194 RNA synthesis 191, 192 and virus infection 189-96 Membrane permeability agents 196-203 ATP 202 ionic concentrations 199-201 ionophores 197-99 lysolethicin 201
measurement 178, 179 picornavirus 184-86 thionins 203 togaviruses 186, 187 viral entry 194, 195 viral macromolecules 195, 196 viral types and effects 183 virus infection 171-204 DNA 188, 189 modification 172 RNA 184-88 Meptazinol in liver disease 460 Misonidazole 392 Monensin structure 198 Mutagenesis and retinoids 40 Mycosis fungoides, retinoids 116-18
Neurokinins 413-15 Neuropeptide Y 415-17 Neurotensin 417,418 Neurotransmitters, autonomic 401-26 novel 405-26 putative 406 release 403,404 Nigericin structures 198 Nitroimidazole analogues 391-96 structure 392-95 Nucleosides, membrane transport 351,352
Opioid peptides
418-20
Peptide histidine isoleucine 422-26 Pharmacokinetics in liver disease 441--46 Phosphonoformate animal treatment 242-52 efficiency 244-49 antiviral effects 277 cellular toxicity 240-42 chemistry 215,216 clinical studies 259-76 CMV infection 265-69 AIDS patients 269-72 bone marrow transplant 265, 268 clinical effects 266 renal transplants 265, 267 CMV sensitivity 227 CMV synthesis 225 DNAase 220 DNA polymerase 219, 220 inhibition model 234, 235 interactions 236 drug combinations 252-55 HIV replication 255 enzymes inhibited 216-24 structure-activity 220-24 fibroblast uptake 241,242 half-life, blood 256 hepatitis B virus infection 272,274 herpes, cutaneous in animals 243-49 herpes, genital in animals 249,250 herpes, genital, clinical studies 260~5 herpes, keratitis 250, 251 herpes, labial, clinical studies 259, 260 herpes, viral excretion 263 HIV infection 272, 273 HIV isolation 273 HIV replication 228, 229, 236,237
SUBJECT INDEX HSV-1 238,239 mechanisms of action 230-40 cell cultures 237--40 cell-free system 230-37 mechanism of inhibition 232, 233 parenteral, safety 275,276 pharmacokinetics 255-58 plasma clearance 257 polymerase activities 222 resistance 252, 253 reverse transcriptions 218, 219 time course 236, 237 RNAase 220 RNA polymerases 217,218 structure 215 toxicology 258, 259 virus multiplication 224-29 cell culture 226 Photohaemolysis, UVA and retinoids 131, 132 Photosensitivity drug-induced 123 retinoid-induced 127, 128 Photosensitization 123 drugs 125 mechanisms 125-27 retinoids 124 Photosensitizers 124, 125 Phototoxicity, cutaneous 127 Platelet activating factor and airway smooth muscle 373-80 bronchospasm 374, 375,378 cough 378 vascular permeability 377, 378 Protein kinase C, retinoid modulation 107 Psoriasis therapy 67-72 see also RePUVA new retinoids 157-66 retinoid actions 157 Psoriatic arthritis, retinoids 164, 165 Pyrimidine synthesis, salvage pathways 350, 351 Pyrophosphate analogues, polymerase inhibition 222, 223
Quinone bioreductive alkylating agents 383-91 mitomycin C 389 structures 384--86,388-91
Radioimmunoassay (RIA), viral antigen 306 RePUVA (retinoid and photochemotherapy) 67-72 mechanisms of action 71 principles 67, 68 protocols 68-70 psoriasis 162, 163 results 68, 69 side effects 70, 71 Resistance, phosphonoformate 252, 253 Retinaldehyde 3--6 Retinoic acid, all-trans- 6--9 mechanism of action 13-16 metabolism, scheme 7 pharmacokinetics 8, 9 utriculus diameter 14 Retinoic acid, c/s (isotretinoin) 9-13 acne 91-104 blood levels 11, 13 bone effects 139, 140 lipid metabolism 58, 59 mechanism of action 13-16
metabolism 12 utriculus diameter 14 Retinoid-binding proteins 45-53 see also cellular retinoic acid binding binding affinities 50 oral mucosa 48, 49 PAGE assay 48 skin 47-49 Retinoids biological efficacy 22 carriers 45-53 cutaneous malignancies 107-19 mechanism of action 29, 31 new, synthetic 158 pharmacology 1-23 photosensitivity 123-33 skin neoplasia 114 skin preneoplasia 110-13 structures 30, 46 target organ toxicity 32-38 therapy and lipid metabolism 55--63 third generation 22, 23 tolerance and dose 31, 32 toxicology 29--40 Retinol 1-3 formula 2 Ribavirin 311
Skeletal hyperostosis 138, 139 Skin carcinogenesis 108, 109 microflora and ache therapy 100, 101 retinoid toxicity 34, 77, 78 Skin cancer basal cell 113 preneoplasia and retinoids 110-13 prevention 109 squamous cell 113 Somatostatin 420-22 Specimen collection and transport, virus 289, 290
Teratogenesis, retinoids 38--40 Toxicity retinoids 29--40 synthetic retinoids 165, 166 Trifiuorothymidine 310
Vasoactive intestinal polypeptide 422-26 Viral diagnosis antigen detection 301-306 cytopathic effects 292, 293 importance 314-16 methods 287-316 rapid 300-309 specimens and disease 289 Viral genome detection 306-9 Virus cell entry modes 173-77 cytopathic effects 193 endocytosis 174 HIV replication stages 331 and membrane permeability 171-204 Virus identification microscopy 298 monoclonal antibodies 295 restriction endonuclease 297, 298 RNA genome analysis 296
vii
viii Virus-induced cellular changes 290, 291 Virus isolation 290-92 cultivation 294, 295 HIV 295 specimen processing 293 Virus multiplication, phosphonoformate 224-29 Virus shapes, RNA and DNA 298-300
SUBJECT INDEX Vitamin A anticancer effects 107 and bone 137, 138 liver storage 145, 146 liver toxicity 145-53 metabolism scheme 4 skin cancer 109