Advances in Pain Management

Advances in Pain Management
Therapeutic

The market for pain management products is expanding constantly and has much potential. Situations where pain management strategies are insufficient are manifold and there are numerous opportunities for new treatment options. Advances in Pain Management will enable you to analyse the current and predicted market for pain management products, the current strategies for pain management in different situations and areas where there is significant clinical need. The report will provide in-depth information on current research into new pain management options, profiling new types of product under investigation and the companies involved.

Contents include traumatic and post-traumatic pain; operative and post-operative pain; dental pain and critical care pain. Treatment of chronic pain associated with a huge range of diseases including arthritis, cancer, diabetes and AIDS is assessed. Muscular aches (including back pain), stress headache and neuralgia are also reviewed in this forthcoming Scrip report.

PUBLICATION: February 2000
REF: BS1040E
PAGES: 150+
PRICE: £495/$1,040/¥119,000

CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
ACKNOWLEDGEMENTS
METHODOLOGY

M.1 Objectives
M.2 Method
M.3 Synopsis
M.4 Limitations
M.5 Currency conversion

ABBREVIATIONS
GLOSSARY

CHAPTER 1 INTRODUCTION AND PRINCIPLES OF PAIN MANAGAMENT
1.1 Introduction - what is pain?
1.1.1 Definition of pain
1.2 Physiology and pathophysiology of pain
1.2.1 Peripheral pain mechanisms
1.2.1.1 Cutaneous nerve endings
1.2.1.2 Cutaneous and non-cutaneous nociceptors
1.2.2 Central pain mechanisms
1.2.2.1 The spinal cord
1.3 Psychology of pain
1.3.1 The role of the emotions
1.3.2 Individual perception and tolerance
1.4 Principles of pain management
1.4.1 Evidence-based medicine
1.4.2 Measuring pain
1.4.3 Ethics of pain management
1.4.4 Genetic issues
1.4.5 Pharmaceutical pain management
1.4.5.1 Analgesia
1.4.5.2 Non-opioid analgesics
1.4.5.3 Opioid analgesics
1.4.6 Adjuvant therapy
1.4.7 Anaesthesia
1.4.7.1 Regional anaesthesia
1.4.7.2 General anaesthesia
1.5 Drug delivery aspects
1.5.1 Pharmaceutical drug delivery routes for pain management
1.5.1.1 Opioid delivery
1.5.1.2 Topical NSAIDs
1.6 Complementary or alternative methods of managing pain
1.6.1 Surgical techniques
1.6.1.1 Laser treatment
1.6.2 Massage and manipulation
1.6.2.1 Massage
1.6.2.2 Manipulation
1.6.2.3 Acupuncture
1.6.2.4 Acupressure
1.6.2.5 Stimulation analgesia
1.6.2.6 Intrasound
1.6.3 Psychological therapy
1.6.4 Natural remedies
1.6.4.1 Homeopathic remedies
1.6.4.2 Herbal remedies
1.6.4.3 Water
1.6.4.4 Sugar
1.6.4.5 Oxygen

CHAPTER 2 PAIN MANAGEMENT IN PRACTICE
2.1 Overview
2.2 Pain associated with surgical trauma
2.2.1 Perioperative pain management
2.2.2 Pre-emptive pain management
2.2.3 Surgical pain management (anaesthesia)
2.2.3.1 Muscle relaxation
2.2.3.2 Minor surgery
2.2.3.3 Anaesthesia in children and newborn babies
2.2.4 Post-operative analgesia
2.3 Non-surgical trauma
2.4 Disease-related pain
2.4.1 Chronic pain
2.4.2 Visceral pain
2.4.3 Disease-related pain - cancer
2.4.3.1 Breakthrough pain
2.4.3.2 The World Health Organization's 'analgesic ladder'
2.4.3.3 Opioid rotation (sequential opioid trials)
2.4.3.4 Limitations to high-dose oral opioids
2.4.3.5 Alternatives
2.4.3.6 Geriatric cancer pain management
2.4.3.7 Paediatric cancer pain management
2.4.4 Disease-related pain - disorders other than cancer
2.4.4.1 Headache and migraine
2.4.4.2 Dental pain
2.4.4.3 Back pain
2.4.4.4 Rheumatic pain
2.4.4.5 Gynaecological and obstetric pain
2.4.4.6 AIDS pain
2.4.4.7 Other pains
2.4.4.8 Bone pain and osteoporosis
2.5 Neuropathic pain
2.5.1 Shingles and post-herpetic neuralgia
2.5.2 Diabetic neuropathy
2.5.3 Phantom limb pain
2.6 Other current pain topics
2.6.1 Paediatric and neonatal pain
2.6.2 Geriatric pain

CHAPTER 3 MARKETED DRUGS
3.1 NSAIDs and other non-opioid agents
3.1.1 Comparison between first-line treatment analgesics
3.1.2 Side effects associated with NSAIDs
3.1.3 Generics
3.2 Profiles of NSAIDs and other non-opioid analgesics on the market
3.2.1 Aceclofenac
3.2.2 Dexketoprofen
3.2.3 Diclofenac
3.2.4 Flurbiprofen
3.2.5 Ibuprofen
3.2.5.1 Ibuprofen + codeine
3.2.5.2 Ibuprofen + hydrocodone
3.2.6 Ketoprofen
3.2.7 Ketorolac
3.2.8 Lornoxicam
3.2.9 Naproxen betainate
3.2.10 Paracetamol
3.2.10.1 Paracetamol + codeine phosphate
3.2.10.2 Paracetamol + dihydrocodeine
3.2.11 Piroxicam-(-cyclodextrin
3.2.12 Propacetamol
3.3 Anticonvulsants
3.3.1 Carbamazepine
3.3.2 Sodium valproate
3.4 Antidepressants
3.4.1 Nefazodone
3.5 Bisphosphontes
3.5.1 Clodronate disodium
3.5.2 Disodium pamidronate
3.6 Opioid analgesics
3.6.1 Morphine
3.6.1.1 Morphine sulphate
3.6.2 Butorphanol
3.6.3 Eptazocine
3.6.4 Fentanyl
3.6.5 Fentanyl citrate
3.6.6 Flupirtine
3.6.7 Hydromorphone
3.6.8 Oxycodone
3.6.9 Tramadol
3.7 Antimigraine agents
3.7.1 Triptans
3.7.1.1 Naratriptan
3.7.1.2 Rizatriptan
3.7.1.3 Sumatriptan
3.7.1.4 Zolmitriptan
3.7.2 Other migraine agents
3.7.2.1 Dihydroergotamine
3.7.2.2 Lomerizine
3.7.2.3 Paracetamol + aspirin + caffeine
3.7.2.4 Paracetamol + domperidone
3.8 Arthritis and anti-inflammatory agents
3.8.1 COX-2 inhibitors
3.8.1.1 Amtolmetin
3.8.1.2 Celecoxib
3.8.1.3 Meloxicam
3.8.1.4 Nimesulide
3.8.1.5 Rofecoxib
3.9 Anaesthetics and muscle relaxants
3.9.1 Inhaled anaesthetics
3.9.1.1 Desflurane
3.9.1.2 Isoflurane
3.9.1.3 Sevoflurane
3.9.2 Induction agents and analgesics
3.9.2.1 Alfentanil
3.9.2.2 Etomidate
3.9.2.3 Midazolam
3.9.2.4 Propofol
3.9.2.5 Remifentanil
3.9.2.6 Sufentanil
3.9.3 Local anaesthetics
3.9.3.1 Amethocaine
3.9.3.2 Bupivacaine
3.9.3.3 Lidocaine (lignocaine)
3.9.3.4 Lidocaine dental delivery system
3.9.3.5 Lidocaine + prilocaine
3.9.3.6 Ropivacaine
3.9.4 Muscle relaxants
3.9.4.1 Oculinum
3.9.4.2 Tizanidine
3.10 Miscellaneous compounds
3.10.1 Capsaicin
3.10.2 Clonidine
3.10.3 Elcatonin
3.10.4 Neurotropin
3.10.5 Nitroglycerin
3.10.6 Sm153 lexidronam

CHAPTER 4 DRUGS IN DEVELOPMENT
4.1 Profiles of NSAIDs and other non-opioid agents in development
4.1.1 NSAIDs
4.1.1.1 Aspirin, Micropump
4.1.1.2 Cizolirtine
4.1.1.3 Diclofenac
4.1.1.4 Flurbiprofen
4.1.1.5 Ibuprofen
4.1.1.6 Ibuprofen + codeine
4.1.1.7 Oxaprozin potassium
4.1.1.8 Piroxicam
4.1.2 Non-opioid analgesics
4.1.2.1 Paracetamol, PharmaZome
4.1.3 Vanilloid receptors
4.1.3.1 Resiniferatoxin
4.1.4 Nitric oxide NSAIDs
4.1.4.1 HCT-3012
4.1.4.2 NCX-4016
4.1.5 Tachykinins (neurokinins)
4.1.5.1 DA-5018
4.1.5.2 FK-888
4.1.5.3 L-758298
4.1.5.4 Lanepitant
4.2 Cholecystokinin antagonists
4.2.1 Colykade
4.2.2 Devacade
4.2.3 Glutamate receptors
4.2.3.1 CNS-5161
4.2.3.2 GV-196771
4.2.3.3 Memantine
4.2.3.4 NMDA antagonist + OTC analgesic
4.2.4 Antidepressants
4.2.4.1 R-fluoxetine
4.2.4.2 Venlafaxine
4.2.5 Anticonvulsants
4.2.5.1 Gabapentin
4.2.5.2 Harkoseride (ADD 234037)
4.2.5.3 Lamotrigine
4.2.5.4 Pregabalin
4.2.5.5 Topiramate
4.2.6 Cholinergic (nicotinic) receptor analgesics
4.2.6.1 ABT-594
4.2.6.2 Eperisone
4.2.6.3 ST-200
4.2.7 Cannabinoids
4.2.7.1 Cannabis-based compound
4.2.7.2 Dronabinol
4.2.8 Bisphosphonates and bone pain
4.2.8.1 Calcitonin, oral and nasal delivery
4.2.8.2 Calcitonin, oral drug delivery system
4.2.8.3 Calcitonin, DermaPulse
4.2.8.4 Calcitonin, PowderJect
4.2.8.5 Ipriflavone
4.2.9 Tripeptides
4.2.9.1 CEE-04-420
4.2.10 Other non-opioid agents
4.2.10.1 117m-Sn-DTPA
4.2.10.2 17.454-JL
4.2.10.3 CKD-303
4.2.10.4 GW-275919
4.2.10.5 HGP-4
4.2.10.6 HP-228
4.2.10.7 Hyaluronic acid
4.2.10.8 LTA
4.2.10.9 NIK-264
4.2.10.10 Nimesulide
4.2.10.11 Prosaptide TX14 (A)
4.2.10.12 ZD-6416
4.3 Opioid compounds
4.3.1 Morphine
4.3.1.1 Morphine-6-glucuronide
4.3.1.2 Morphine (DepoMorphine)
4.3.1.3 Morphine, AERx Pain Management System
4.3.1.4 Morphine, Multipor technology
4.3.1.5 Morphine sulphate
4.3.1.6 Pulmonary-delivered morphine sulphate
4.3.2 Other morphine compounds
4.3.3 Conorfone
4.3.3.1 Propiram fumarate
4.3.4 Various strength opioid analgesics using OROS technology
4.3.5 Various strength analgesics using Geomatrix technology
4.3.6 Fentanyl, AERx Pain Management System
4.3.7 Buprenorphine
4.3.8 Asimadoline
4.3.9 TRK-820
4.3.10 LEF (BCH-3963)
4.3.11 Loperamide
4.3.12 Oxycodone and oxycodone combinations
4.3.12.1 Oxycodone + ibuprofen
4.3.12.2 Oxycodone + paracetamol
4.3.13 DPI-3290
4.3.14 ADL-10-0101
4.3.15 Xorphanol
4.3.16 TSN-09
4.3.17 NMDA antagonist + opioid compounds
4.3.17.1 Dextromethorphan + hydrocodone
4.3.17.2 Dextromethorphan + morphine
4.3.17.3 Dextromethorphan + oxycodone + paracetamol
4.4 Antimigraine agents
4.4.1 Triptans
4.4.1.1 Almotriptan
4.4.1.2 ALX-0646
4.4.1.3 Eletriptan
4.4.1.4 Frovatriptan
4.4.1.5 IS-159
4.4.2 Other antimigraine agents
4.4.2.1 BIBN-4096
4.4.2.2 Dotarizine
4.4.2.3 KT2-962
4.4.2.4 MT-100
4.4.2.5 MT-300
4.4.2.6 MT-500
4.4.2.7 Pulmonary-delivered migraine therapy
4.4.2.8 Tenosal
4.4.2.9 Tonabersat
4.5 Non-opioid anti-inflammatory analgesic agents
4.5.1 COX-2 inhibitors
4.5.1.1 COX-189
4.5.1.2 Darbufelone
4.5.1.3 JTE-522
4.5.1.4 L-791456
4.5.1.5 MK-663
4.5.1.6 Parecoxib
4.5.1.7 S-2474
4.5.1.8 T-614
4.5.1.9 TS-932
4.5.1.10 Valdecoxib
4.5.2 Other arthritis/anti-inflammatory agents
4.5.2.1 Benzydamine flufenamate
4.5.2.2 Diclofenac
4.5.2.3 Eltenac
4.5.2.4 Filenadol
4.5.2.5 IPR-6001
4.5.2.6 Ketoprofen
4.5.2.7 R-ketoprofen
4.5.2.8 ML-3000
4.5.2.9 Naproxen
4.5.2.10 NRD-101
4.5.2.11 Pelubiprofen
4.6 Anaesthetics
4.6.1 Induction agents and anaesthetics
4.6.1.1 Dexmedetomidine
4.6.2 Local anaesthetics
4.6.2.1 Bupivacaine
4.6.2.2 Levobupivacaine
4.6.2.3 Lidocaine/lignocaine formulations
4.6.2.4 RSD-921
4.6.2.5 Tetracaine
4.7 Muscle relaxants
4.7.1 AN-072
4.7.2 Lanperisone
4.7.3 Rapacuronium bromide
4.8 Miscellaneous compounds
4.8.1 Contulakin-G (CGX-1160)
4.8.2 Human chorionic gonadotrophin
4.8.3 P-07
4.8.4 Ziconotide
4.9 Early research
4.9.1 Destruction of pain transmitting neurons
4.9.1.1 Injectable toxins attached to substance P
4.9.1.2 Immunotoxins
4.9.1.3 (-opiate receptor
4.9.2 Neural cells
4.9.3 Adenosine triphosphate and adenosine
4.9.4 Neurotrophic factors
4.9.5 (-opioid receptors
4.9.6 Heterodimers
4.9.7 Sodium channel blockers
4.9.8 Other research
4.9.8.1 Gene therapy for nerve growth factor
4.9.8.2 Pain anticipation
4.9.8.3 Histamine
4.9.8.4 Bradykinin
4.10 Drug delivery systems/devices for pain drugs
4.10.1 SEPA - MacroChem
4.10.2 PowderJect - PowderJect Pharmaceuticals
4.10.3 Geomatrix - SkyePharma
4.10.4 AERx Pulmonary Drug Delivery System - Aradigm
4.10.4.1 AERx Pain Management System
4.10.5 DermaPulse - Genetronics
4.10.6 DepoFoam - SkyePharma
4.10.7 Transfersomes - IDEA
4.11 Summary of drug development trends
4.11.1 General trends
4.11.2 Analgesics
4.11.3 Opioids
4.11.4 Anaesthetics
4.11.5 Other mechanisms of action

CHAPTER 5 MARKET OVERVIEW AND EPIDEMIOLOGY
5.1 Market value
5.1.1 Net present value definition
5.1.2 Drug class and type of pain
5.1.2.1 Analgesics
5.1.2.2 Anaesthetics
5.1.2.3 Other
5.1.2.4 New drugs for different types of pain
5.1.3 Market value by geographical region
5.1.3.1 Market value for CNS and musculoskeletal drug classes
5.1.3.2 Market value for pain drugs by geographical region
5.2 Market growth and forecasts
5.2.1 World pain market
5.2.2 World market by drug class
5.2.2.1 Analgesics
5.2.2.2 Migraine
5.2.2.3 Other analgesics
5.2.2.4 Arthritis/anti-inflammatory-related analgesics
5.2.2.5 Anaesthetics and muscle relaxants
5.2.2.6 Calculation of values
5.2.3 World market by product
5.2.3.1 Analgesic drugs for pain
5.2.3.2 Analgesic drugs for migraine
5.2.3.3 Arthritis/anti-inflammatory drugs
5.2.3.4 Market forecast for European over-the-counter products
5.3 Market structure
5.3.1 Pain types
5.3.2 Pain categories for US companies
5.3.3 Drug class
5.3.3.1 Opioids (consumption)
5.3.3.2 Geographical regions
5.4 Major products
5.4.1 Pain drugs rank
5.4.1.1 Analgesic drugs rank alone
5.4.1.2 Anaesthetics/muscle relaxants drug rank
5.4.1.3 Antimigraine
5.4.1.4 Arthritis/inflammation
5.5 Market trends
5.5.1 Short-term trends
5.5.2 Long-term trends
5.6 Epidemiology
5.6.1 Current statistics
5.6.1.1 The growing and ageing population
5.6.1.2 The cost of illness
5.6.2 Incidence and prevalence
5.6.2.1 Incidence and prevalence of chronic pain
5.6.2.2 Statistics for acute pain

CHAPTER 6 COMPANY PROFILES
6.1 Akzo Nobel
6.2 ALZA
6.3 Abbott Laboratories
6.4 AstraZeneca
6.5 Aventis
6.6 Bristol-Myers Squibb
6.7 Eisai
6.8 Forest Laboratories
6.9 Glaxo Wellcome
6.10 Johnson & Johnson
6.11 Knoll
6.12 Lilly
6.13 Pharmacia & Upjohn
6.14 Roche
6.15 Shionogi
6.16 Warner-Lambert (Parke-Davis)

CHAPTER 7 COMPANY DIRECTORY

REFERENCES
APPENDIX I USEFUL WEBSITES
APPENDIX II DRUGS IN PRECLINICAL DEVELOPMENT

List of Tables
Table M.1 Annual average exchange rates against the US$, 1997-1999

Table 1.1 A classification of NSAIDs

Table 2.1 Overview of the different types of pain

Table 5.1 Net present values of various therapeutic categories compared considering medical need versus patient population, 1998
Table 5.2 CNS and musculoskeletal drug sales in retail pharmacies in the 12 months to September 1999 ($ million)
Table 5.3 Sales forecasts for the different pain drug classes worldwide, 1997-2002
($ million)
Table 5.4 Potential worldwide sales in 2002 and overall peak sales of selected analgesics
Table 5.5 Potential worldwide sales in 2002 and overall peak sales of selected antimigraine drugs
Table 5.6 Potential worldwide sales in 2002 and overall peak sales of selected arthritis and anti-inflammatory drugs
Table 5.7 Potential worldwide sales in 2002 and overall peak sales of selected anaesthetics and muscle relaxants
Table 5.8 Average daily consumption of DDD of morphine per million inhabitants, 1993-1997
Table 5.9 Top 10 pain/anaesthetic-related drugs worldwide, ranked according to sales predictions for 1999
Table 5.10 Top five anaesthetics and muscle relaxants worldwide, ranked according to sales predictions for 1999
Table 5.11 Top five antimigraine drugs worldwide, ranked according to sales predictions for 1999
Table 5.12 Top five arthritis/anti-inflammation drugs for pain worldwide, ranked according to sales predictions for 1999

Table 6.1 Akzo Nobel's financial results, 1994-1999 (NLG million)
Table 6.2 Akzo Nobel's major pain/anaesthetic products
Table 6.3 Akzo Nobel's/Organon's major pain/anaesthetic products in development
Table 6.4 ALZA's financial results, 1994-1999 ($ thousand)
Table 6.5 ALZA's major pain/anaesthetic products in development
Table 6.6 Abbott's financial results, 1994-1999 ($ million)
Table 6.7 Abbott's major pain/anaesthetic products
Table 6.8 Abbott's major pain/anaesthetic products in development
Table 6.9 AstraZeneca's financial results, 1998-1999 ($ million)
Table 6.10 Astra's financial results, 1994-1997 (SKr million)
Table 6.11 Zeneca's financial results, 1994-1997 (� million)
Table 6.12 AstraZeneca's major pain/anaesthetic products
Table 6.13 AstraZeneca's major pain/anaesthetic products in development
Table 6.14 Hoechst group's financial results, 1994-1998 (DM million)
Table 6.15 Aventis' major pain/anaesthetic products
Table 6.16 Bristol-Myers Squibb's financial results, 1994-1999 ($ million)
Table 6.17 Eisai's financial results, 1995-1999 (� million)
Table 6.18 Forest Laboratories' financial results, 1995-1999 ($ thousand)
Table 6.19 Glaxo Wellcome's financial results, 1994-1999 (� million)
Table 6.20 Glaxo Wellcome's major pain/anaesthetic products
Table 6.21 Glaxo Wellcome's pain/anaesthetic products in development
Table 6.22 Johnson & Johnson's financial results, 1994-1999 ($ million)
Table 6.23 Johnson & Johnson's marketed pain and anaesthetic products
Table 6.24 Johnson & Johnson's major pain/anaesthetic products in development
Table 6.25 BASF Group's financial results, 1994-1998 (DM million)
Table 6.26 Knoll's major pain/anaesthetic products
Table 6.27 Lilly's financial results, 1994-1999 ($ million)
Table 6.28 Lilly's major pain/anaesthetic products in development
Table 6.29 Pharmacia & Upjohn's financial results, 1994-1999 ($ million)
Table 6.30 Pharmacia & Upjohn's major pain/anaesthetic products in development
Table 6.31 Roche's financial results, 1994-1999 (SwFr million)
Table 6.32 Roche's major pain/anaesthetic products
Table 6.33 Roche's pain/anaesthetic products in development
Table 6.34 Shionogi's financial results, 1994-1999 (� million)
Table 6.35 Shionogi's pain/anaesthetic products in development
Table 6.36 Warner-Lambert's financial results, 1994-1999 ($ million)
Table 6.37 Warner-Lambert's major pain/anaesthetic products in development

Table A.1 NSAID analgesics in preclinical development, 1999
Table A.2 Non-NSAID analgesics in preclinical development, 1999
Table A.3 Antimigraine analgesics in preclinical development, 1999
Table A.4 Anaesthetics in preclinical development, 1999
Table A.5 Muscle relaxants in preclinical development, 1999

List of figures
Figure 1.1 Nerve tracts in the spinal cord

Figure 5.1 Medicines in development in the US for neurological disorders, 1999
Figure 5.2 Total pain market forecast, 1997-2002
Figure 5.3 Forecast for the European non-prescription pain relief market, 1997-2003
Figure 5.4 Structure of the worldwide analgesia market, 1999
Figure 5.5 Worldwide analgesic prescriptions for acute and chronic pain, 1999
Figure 5.6 Pain drugs in development with respect to US neurological market, 1999
Figure 5.7 The European non-prescription pain relief market by country, 1997
Figure 5.8 DALYs attributable to injuries in low and middle income countries, 1998