Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
By
Prof. K. K. Jain
MD, FRACS, FFPM
Jain PharmaBiotech
Basel, Switzerland
July 2012
AUTHOR'S
BIOGRAPHY
July 2012
Copyright 2012 by
Jain PharmaBiotech
Blsiring 7
CH-4057 Basel
Switzerland
Tel & Fax:
Email:
Web site:
+4161-6924461
info@pharmabiotech.ch
http://pharmabiotech.ch/
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, or otherwise without the prior written
permission of the Publisher. This report may not be lent, resold or otherwise traded in any manner without the
consent of the Publisher. While all reasonable steps have been taken to ensure the accuracy of the information
presented, the Publisher cannot accept responsibility for inadvertent errors or omissions.
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TABLE
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Substance P ............................................................................................................... 51
Excitatory amino acids ................................................................................................. 51
Role of nitric oxide in pain ............................................................................................ 52
Prostaglandins ............................................................................................................ 52
Endocannabinoids ....................................................................................................... 53
Protein kinase C .......................................................................................................... 53
Adenosine and adenosine receptors ............................................................................... 54
Vitamin D and pain ...................................................................................................... 54
Vanilloid receptor ........................................................................................................ 54
TRPA1 and TRP V1 receptors ............................................................................................ 54
Endothelin-B receptors ................................................................................................ 56
Nerve growth factor and pain ....................................................................................... 56
Adrenomedullin as a pain-related peptide....................................................................... 56
Biomarkers of pain ........................................................................................................... 56
Biomarkers of visceral pain .......................................................................................... 57
3. Pharmacotherapy of Pain...................................................................... 75
Introduction....................................................................................................................... 75
Mechanism of action of currently used pain medications ................................................... 75
Non-steroidal antiinflammatory drugs ............................................................................... 76
COX-2 inhibitors .............................................................................................................. 76
Celecoxib ................................................................................................................... 77
Metamizole ................................................................................................................. 78
Nimesulide ................................................................................................................. 78
Rofecoxib ................................................................................................................... 78
Valdecoxib ................................................................................................................. 79
Lumiracoxib ............................................................................................................... 79
Side effects of COX inhibitors........................................................................................ 80
Innovative COX-2 inhibitors in development ................................................................... 81
Acetaminophen ................................................................................................................ 82
Antioxidants as analgesics ................................................................................................. 82
Opiates and opioids ........................................................................................................... 83
Innovations in opioid therapy ............................................................................................ 83
Oral transmucosal fentanyl ........................................................................................... 84
Use of opioids for chronic non-cancer pain ..................................................................... 84
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Introduction..................................................................................................................... 323
Profiles of companies ....................................................................................................... 323
Collaborations .................................................................................................................. 492
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2-1: IASP guidelines for the use of animals in pain studies ..................................................... 62
2-2: Chronic pain as a manifestation of other diseases ........................................................... 63
2-3: Recommendations for assessing patient satisfaction with pain management ...................... 68
3-1: Classification of some currently used pain medications according to mechanism ................. 75
3-2: Drugs used for the treatment of pain ............................................................................ 75
3-3: Selective COX-2 inhibitors in clinical use for pain ............................................................ 77
3-4: Antiepileptic drugs with analgesic effect ........................................................................ 91
3-5: Companies with products to deter abuse of opioids ....................................................... 102
4-1: Non-pharmacological approaches to management of pain.............................................. 108
4-2: Companies involved in neuromodulation therapy for pain .............................................. 114
4-3: Reasons for the inadequate management of acute pain ................................................. 116
4-4: Causes of chronic backache ....................................................................................... 133
4-5: Management of chronic pelvic pain ............................................................................. 135
4-6: Management of pain in cancer ................................................................................... 136
4-7: Definitions of tolerance, physiological dependence, withdrawal and addiction ................... 142
4-8: A simplified classification of headache ......................................................................... 143
4-9: Various methods for the management of migraine ........................................................ 144
4-10: Management of neuropathic pain based on mechanism and diagnosis ........................... 153
4-11: Management of central neuropathic pain ................................................................... 156
4-12: Current management of peripheral diabetic neuropathy .............................................. 159
4-13: Treatment strategies for postherpetic neuralgia .......................................................... 161
4-14: Management of complex regional pain syndrome ........................................................ 163
4-15: Methods of treating phantom limb pain ..................................................................... 165
4-16: Treatment of chronic unexplained pain due to central sensitization ............................... 171
4-17: Anti-itching therapies .............................................................................................. 172
4-18: Suggested improvements in the management of pain ................................................. 182
5-1: A classification of drug delivery methods used in management of pain ............................ 185
5-2: Selected marketed non-injection drug delivery systems for pain..................................... 190
5-3: Spinal administration of drugs for pain ........................................................................ 204
5-4: Selected drug delivery systems for pain in clinical development ..................................... 210
6-1: Classification of drugs in development for pain ............................................................. 213
6-2: Preclinical studies on cannabinoid (CB2) receptor agonists as analgesics ......................... 218
6-3: Cannabinoid receptor agonists in clinical development as analgesics ............................... 219
6-4: NO-related therapies for pain ..................................................................................... 236
6-5: Major opioids receptors and their ligands..................................................................... 239
6-6: Strategies to counteract pain at various levels at periphery and in the CNS ..................... 245
6-7: Types of TRPV1 antagonists ....................................................................................... 246
6-8: TRPV1 antagonists in clinical trials .............................................................................. 246
6-9: Experimental gene therapy approaches for relief of pain ............................................... 254
6-10: Selected preclinical approaches to pain therapy .......................................................... 262
6-11: Selected preclinical drugs for neuropathic pain ........................................................... 263
6-12: Selected clinical trials of miscellaneous drugs for pain ................................................. 270
6-13: Selected clinical trials of drugs for postsurgical pain .................................................... 273
6-14: COX-2 inhibitors in clinical development .................................................................... 275
6-15: Disease modifying drugs for arthritis in clinical trials ................................................... 275
6-16: Clinical trials of drugs for neuropathic pain ................................................................ 277
6-17: Selected drugs in clinical development for migraine .................................................... 287
6-18: Therapeutic targets for treating visceral pain ............................................................. 290
8-1: Market values for various painful conditions 2011-2021 ................................................ 299
8-2: Changes in market shares of drugs for neuropathic pain 2011-2021 ............................... 301
8-3: Markets for pain according to therapies 2011-2021 ...................................................... 302
8-4: Distribution of value of pain therapeutics in major markets 2011-2021 ........................... 305
8-5: Distribution of value of opioids in major pain markets 2011-2021 ................................... 305
8-6: Distribution of value of NSAIDs in major pain markets 2011-2021 .................................. 305
8-7: Strategies for developing pain markets ....................................................................... 307
9-1: P450 isoforms in the metabolism of drugs used in the management of pain ..................... 319
10-1: Product pipeline of Adolor Corporation....................................................................... 329
10-2: Selected collaborations in the area of pain management .............................................. 492
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