[...]... expression in spinal cord neurons and other regions of the CNS, and elevated prostaglandin E2 levels in the cerebrospinal fluid The intraspinal administration of COX-2 inhibitors decreased both the inflammation-induced central prostaglandin E2 levels and mechanical,133 or thermal134 hyperalgesia In contrast COX-1 inhibitors were only effective systemically and not when injected intraspinally Alzheimer’s... to PGD2 in the sleep-wake regulation cycle.129 PGD2 seems to be the major COX metabolite in the brain, where in Aic22-01.qxd 18 9/11/02 12:56 PM Page 18 Recent Advances in Anaesthesia and Intensive Care 22 addition to the sleep-wake cycle it is known to be involved in homoeostatic temperature balance.129 COX-1 and COX-2 are both localised in the brain and spinal cord COX-2 is mainly expressed in the... patients taking aspirin, Aic22-01.qxd 16 9/11/02 12:56 PM Page 16 Recent Advances in Anaesthesia and Intensive Care 22 the annualised incidence rates of upper gastrointestinal ulcer complications alone and combined with symptomatic ulcers for celecoxib to diclofenac and ibuprofen were 2.01% (celecoxib) and 2.12% (diclofenac and ibuprofen) Fewer celecoxib-treated patients than diclofenac and ibuprofen... Recent Advances in Anaesthesia and Intensive Care 22 Inhibition of Prostanoid Biosynthesis: NSAIDs and COX-2 Inhibitors The main therapeutic uses of the NSAID inhibitors of prostanoid biosynthesis are in inflammation and mild-to-moderate pain.72 Elevated concentrations of prostanoids have been observed in almost all forms of human acute and chronic inflammatory conditions studied PGE 2and PGI2 at physiological... formation and pain, but strongly synergise with directly acting pro-inflammatory mediators, such as bradykinin and histamine to cause plasma exudation73 and pain.74 Furthermore, PGE2 is also a potent pyrogenic factor.75 NSAIDs – Non-selective COX Inhibitors In 1971, Vane showed that aspirin, indomethacin and salicylate all inhibited COX activity.76 Since then, three different mechanisms of inhibition... ions.124 In rats, both selective and non-selective COX inhibitors decrease plasma renin activity.125,126 In human beings NSAIDs use leads to an increased risk of renal side-effects, though the incidence is much lower than gastrointestinal side-effects.127 Interestingly, it appears that COX-2 is constitutively expressed in the kidney and influences salt and fluid resorption This may well explain why clinical... role for COX-2 in the gastrointestinal tract, as COX-2 is also found at sites of gastric ulceration where it aids in the healing response Similarly the administration of COX-2 inhibitors slows ulcer healing in animal models.106–108 Gastrointestinal tract: clinical perspective The most common side-effects of NSAIDs are dyspepsia, and injury to the gastrointestinal mucosa This injury in most patients... following for instance volume depletion, and PGI2 in particular becomes essential to sustaining renal vasodilatation and blood flow In animal kidneys COX-1 and COX-2 are co-localized in the macula densa,123 while in man COX-2 appears most associated with podocytes In addition, COX-2 has been identified in a subset of thick ascending limb cells, where it has been suggested to be involved in the handling... remains to be established Reproduction Physiologically, PGF2␣ is the main product of the uterine endometrium, and has been extensively studied in the utero-genital tract, being implicated in reproduction and induction of labour and parturition.148,149 There is strong evidence from receptor knockout studies in the mouse that PGE2 and PGF2␣, and their respective E prostaglandin (EP) and F prostaglandin... taking NSAIDs have a reduced risk of developing Alzheimer’s disease.135 The protective effects of NSAIDs in this setting are most likely related to reduction of inflammation as acetaminophen (paracetamol) is without effect.136 COX-2 expression is increased in the frontal cortex,137 and COX-1 and COX-2 is increased in the temporal cortex138 in Alzheimer’s disease The link between the prostaglandins and . alt="" Recent Advances in Anaesthesia and Intensive Care 22 Aic22-FM.qxd 9/11/02 1:40 PM Page i This page intentionally left blank LONDON ᭹ SAN FRANCISCO Recent Advances in Anaesthesia and Intensive. issues in anaesthesia and intensive care 223 E. Hallinan, N.J.H. Davies 11. Education and training in anaesthesia 237 G. Stanley, J.N. Cashman 12. Resuscitation 259 E. Rowland, H. Binns Index. result of the high standards of training and of equipment. In their chapter on Legal Issues in Anaesthesia and Intensive Care, the principles behind legal actions for clinical negligence are