Prostaglandin synthesis, aspirin

Summation - different mechanisms of action are involved with the same effects for each. Analgesia can be achieved by stimulating opiate receptors (codeine) and blocking prostaglandin synthesis (aspirin). 

Various NSAIDs, such as ibuprofen, indomethacin, ketoprofen, phenylbutazone, piroxicam, and oxyphenbutazone, can decrease renal creatinine and lithium clearance by their common inhibitory action on prostaglandin synthesis. Aspirin (acetylsalicylic acid) and sulindac have not been found to increase lithium plasma steady-state concentrations. ... 

Unsaturated fatty acids increase zinc absorption [27] by their action on prostaglandin synthesis aspirin, perhaps by inhibition of the synthesis of prostaglandin, decreases it [14]. 

Take Two Aspirin and. . Inhibit Your Prostaglandin Synthesis... 

Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231 232-235... 

Aspirin, non-acetylated salicylates, and other NSAIDs have analgesic, antipyretic, and anti-inflammatory actions. These agents inhibit cyclooxygenase (COX-1 and COX-2) enzymes, thereby preventing prostaglandin synthesis, which results in reduced nociceptor sensitization and an increased pain threshold. NSAIDs are the preferred agents for mild to moderate pain in situations that are mediated by prostaglandins (e.g., rheumatoid... 

Prostaglandins inhibit the secretion of protons by the parietal cells in the stomach, which is normally increased in response to food and the hormone gastrin. Consequently, inhibition of prostaglandin synthesis by aspirin or other similar drugs results in increased secretion of protons by the stomach, which can result in considerable gastric discomfort and can, if chronic, lead to the development of a peptic ulcer. Consequently, there is some conflict between the use of such inhibitors to relieve chronic pain (see below), in diseases such as arthritis, and the risk of development of ulcers. 

Pharmacology The site and mechanism of the analgesic effect is unclear. APAP reduces fever by a direct action on the hypothalamic heat-regulating centers, which increases dissipation of body heat (via vasodilatation and sweating). APAP is almost as potent as aspirin in inhibiting prostaglandin synthetase in the CNS, but its peripheral inhibition of prostaglandin synthesis is minimal. 

Hypersensitivity to salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs). Use extreme caution in patients with history of adverse reactions to salicylates. Cross-sensitivity may exist between aspirin and other NSAIDs that inhibit prostaglandin synthesis, and aspirin, and tartrazine. Aspirin cross-sensitivity does not appear to occur with sodium salicylate, salicylamide, or choline salicylate. Aspirin hypersensitivity is more prevalent in those with asthma, nasal polyposis, chronic urticaria. 

Aspirin and related salicylates are the primary treatment for mild to moderate pain, such as that associated with headache, joint and muscle pain, and dysmenorrhea. At higher doses aspirin is an effective analgesic in rheumatoid arthritis (see Chapter 36). The analgesic effects of salicylates are thought to be due to the inhibition of prostaglandin synthesis in the periphery and to a less well documented mechanism at cortical areas. 

The peripheral component of their analgesic action is due to the inhibition of prostaglandin synthetase and thereby inhibiting the synthesis of prostaglandins (PGs) which sensitise the pain receptors to mechanical and chemical stimuli. Aspirin inhibits prostaglandin synthesis and blocks the sensitization of pain mechanism. 

The synthesis of kinins can be inhibited with the kallikrein inhibitor aprotinin. Actions of kinins mediated by prostaglandin generation can be blocked nonspecifically with inhibitors of prostaglandin synthesis such as aspirin. Conversely, the actions of kinins can be enhanced with ACE inhibitors, which block the degradation of the peptides. Indeed, as noted above, inhibition of bradykinin metabolism by ACE inhibitors contributes significantly to their antihypertensive action. 

Additive - the drugs have the same biochemical mechanism and will react with the target cells as long as receptor sites are available. Examples are the cyclooxygenase inhibitors (prostaglandin synthesis inhibitors) aspirin and acetaminophen (Tylenol ), antihypertensives propanolol and the rauwolfia alkaloids. 

Many of the foregoing acids have been shown to inhibit prostaglandin synthesis. This involves several enzymic reactions and it is the first step, mediated by cyclooxygenase, that is usually stopped (Scheme 5). Aspirin has been shown to acetylate the enzyme, destroying its activity, but indomethacin and the arylacetic acids appear to compete with arachidonic acid for the active site on the enzyme. 

Vane, J.R. Inhibition of Prostaglandin Synthesis As a Mechanism of Action for Aspinn-Likc Drugs, Nature-New Biology, 231(25), 232 (June 23, 1971). Weissmann, G. Aspirin. Sci. Amer., 84 (January 1991). 

Finally, sulfinpyrazone (Anturane) is usually administered to treat gouty arthritis, but has also shown some antithrombotic properties because of an ability to decrease platelet function. Sulfinpyrazone decreases platelet aggregation by inhibiting prostaglandin synthesis in a manner similar to aspirin. Sulfinpyrazone can be used as an alternative to aspirin in pre-... 

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