Haemodynamics and Immune Defence: Discoveries in Pharmacology, Second Edition, Volume Three presents selected articles from the historic Discoveries in Pharmacology series that are enhanced with commentary from contemporary scholars who discuss the reception and importance of each chapter along with an updated bibliography on the subject and contributions from those involved in Nobel Prize winning discoveries and pioneering advancements in Pharmacology. This volume brings forth discussions on key discoveries in hemodynamics and immune defense, including chapters on penicillin by Dr. Selwyn and asthma by Dr. Brocklehurst. Academic and industry researchers in pharmacology and medicine, as well as advanced students in the area, will find this useful teaching tool and launch to new discoveries. Chapters can also be used to supplement course material in pharmacology and medical courses. It will also be of interest to those who are interested in the history of medicine.

Dipyrone is widely acknowledged to be an effective antipyretic analgesic with an additional intrinsic spasmolytic activity. It has stood the test of time over the last 75 years in many clinical settings throughout the world. Some 20 years ago, however, concern arose over the implications of isolat ed reports of agranulocytosis following use of dipyrone. Based on these initial cases the Swedish authorities ordered the withdrawal of the drug from the market. Subsequently, dipyrone has been subjected to extensive comparative epidemiological and clinical studies. The results of these in vestigations have allayed the earlier concerns and have shown dipyrone to be a versatile analgesic drug with an overall risk of serious adverse events lower than most other non-opioid analgesics. Based on these results, the Swedish authorities (Lakemedelsverket) have approved the reintroduc tion of dipyrone to clinical use as a valuable contribution to pain treat ment. In connection with this further milestone in the story of the drug, a symposium was held in Stockholm on March 14, 1996, under the chairman ship of Professor N. Rawal to review the current understanding of the ac tion, efficacy and safety of dipyrone. The highlights of this Hoechst symposium emphasize particularly the therapeutic basis for the use of dipyrone in the modern treatment of acute post-operative pain. 9 Mode of action of dipyrone Professor K. Brune, M. D. Erlangen, Germany Most non-opioid analgesic drugs are inhibitors of cydo-oxygenase, the en zyme catalysing the formation of prostaglandins (PGs).

There is no ideal analgesic and the most potent drug is not always the best because of its side-effects. Non-opioid analgesics, including the non-steroi- dal anti-inflammatory drugs and the non-narcotic analgesics, play an im- portant role in the relief of a wide spectrum of painful conditions, though they vary in efficacy and safety. This book reviews the role which non-opi- oid analgesics play in the relitff of pain, particularly with regard to post- operative and cancer pain. Emphasis is placed on the clinical indications for the non-acidic analgesic, dipyrone, and its relative safety in comparison to other non-opioid anlgesics. Michael J. Parnham 9 Introductory remarks Klaus A. Lehmann, Department of Anaesthesiology and Operative Intensive Care, University of Cologne, J osef-Stelzmann-Str. 9, D-50924 Cologne, Germany Opioids are considered to be the most potent analgesics for the manage- ment of acute and chronic pain. Much progress has been achieved with respect to their general availability in most countries, and health care per- sonnel have been encouraged to use these drugs more generously in a vari- ety of pain syndromes, including post-operative or cancer pain. The intro- duction of new techniques such as Patient-Controlled Analgesia (PCA) or guidelines such as the WHO ladder concept for cancer pain mangement have considerably increased our knowledge of their benefits and prob- lems.

Many effective analgesic drugs are available for the relief of acute pain, but their clinical use is widely regarded as being inadequate. The reasons cited for this include concern about the adverse effects of opioids and also insufficient adjustment of therapy to the patient's needs. Non-opioid anal- gesics are the staple drugs for mild to moderate pain and are generally better tolerated than opioid drugs. Differences exist, however, among the non-opioid analgesics which affect the choice of drug for individual pa- tients and specific acutely painful conditions. In an associated symposium of the 7th International Symposium: The Pain Clinic, held in Istanbul, Turkey, the ways were discussed in which treatment with non-opioid analgesics can be tailored to meet the needs of individual patients with acute pain. The highlights of this Hoechst sympo- sium, emphasize the distinctions between the non-steroidal anti-inflamma- tory drugs, and the non-acidic antipyretic analgesics, particularly dipyrone. 9 Mechanisms of action of non-opioid analgesics Professor F. C. Tulunay, M.D. Ankara, Turkey The non-opioid analgesics are among the oldest class of synthetic drugs still in widespread clinical use. They can be divided into the non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, and the non-acidic, antipyretic analgesics, paracetamol and dipyrone. The pharma- cology of these various agents will be reviewed briefly.