Some NSAIDs inhibit phosphodiesterase, which elevates the intracellular concentrations of cyclic AMP. Clinical analgesic efficacy does not necessarily correlate with anti-inflammatory effects and the analgesic action of some compounds such as paracetamol occurs in the absence of anti-inflammatory activity. It is not always possible to distinguish between the anti-inflammatory and analgesic effects of NSAIDs. Similarly, there is evidence to suggest that coxibs also cross this barrier and may exert a central effect in addition to their peripheral effects. Paracetamol (acetaminophen) does cross this barrier and appears to exert its main antipyretic and analgesic effects in the CNS. Most NSAIDs, however, cross the blood–brain barrier poorly. As well as their peripheral anti-inflammatory actions, some NSAIDs may also have a central component to pain relief and even have centrally mediated anti-inflammatory actions. Inhibition of prostaglandin synthesis may only partially explain the therapeutic effects of NSAIDs. It is thought that inhibition of LOX helps preserve mucosal integrity, is anti-inflammatory and, in conjunction with inhibition of COX, provides analgesia comparable to other NSAIDs. Leukotrienes are inflammatory, active in a number of tissues and have a negative effect on the microcirculation of gastrointestinal mucosa, leading to a loss of the protective mucosal barrier. The concept is to inhibit lipoxygenase and the formation of leukotrienes. This target has been active for a while in human medicine however, no compounds have come to market yet. Peter D Hanson, Jill E Maddison, in Small Animal Clinical Pharmacology (Second Edition), 2008 Non-cox-related mechanisms of actionĪ relatively new approach in small animal practice is the use of dual COX/LOX inhibitors. This agent may therefore have a role in the treatment of ocular allergy Kaminuma et al (1998). IL-5 is an important growth and chemotactic factor for eosinophils. Reduction of signs of allergic conjunctivitis has been observed in an animal model.īetotastine besilate is a potent inhibitor of the cytokine IL-5. FK506 and cyclosporine have been shown to inhibit mast cell proliferation and survival.
MK-571 is a selective and potent leukotriene D4 receptor antagonist that blocks leukotriene D4-induced bronchospasm in several animal models Chung (1995).Ī synthetic peptide (Asp-Ser-Asp-Pro-Arg) HEPP ophthalmic solution (Pentyde) has been shown to be effective in allergic conjunctivitis Floyd et al (1988).įK506 has demonstrated potential in the treatment of ocular allergy. MK-886 has potent in vitro and in vivo effects on leukotriene production Brideau (1992). By modifying the action of FLAP, 5-lipoxygenase is unable to fully activate leukotriene synthesis. FLAP plays a role in activating the 5-lipoxygenase enzyme, which catalyses the production of leukotrienes. MK-886 binds to and modifies the activity of the 5-lipoxygenase activating protein (FLAP). REV 5901 has been shown to be the most potent lipoxygenase inhibitor in decreasing lens protein-induced ocular inflammation in a rabbit model Chiou and Chiou (1985). Lipoxygenase inhibitors are under investigation as a therapy for ocular allergy. Lipoxygenase inhibitors, REV 5901 lipoxygenase modulators, MK-886 and leukotriene receptor antagonists, MK-571
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