Prostaglandins aspirin dose

The answer is b. (Hardman, pp 890-891.) Nicotinic acid in large doses stimulates the production of prostaglandins as shown by an increase in blood level. The flush may be prevented by the prior administration of aspirin, which is known to block synthesis of prostaglandins... 

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 NSAIDs (eg, indomethacin, ibuprofen see Chapter 36) block both prostaglandin and thromboxane formation by reversibly inhibiting COX activity. The traditional NSAIDs are not selective for COX-1 or COX-2. Selective COX-2 inhibitors, which were developed more recently, vary—as do the older drugs—in their degree of selectivity. Indeed, there is considerable variability between (and within) individuals in the selectivity attained by the same dose of the same NSAID. Aspirin is an irreversible COX inhibitor. In platelets, which are anuclear, COX-1 (the only isoform expressed in mature platelets) cannot be restored via protein biosynthesis, resulting in extended inhibition ofTXA2 biosynthesis. 

Renal clearance of lithium is reduced about 25% by diuretics (eg, thiazides), and doses may need to be reduced by a similar amount. A similar reduction in lithium clearance has been noted with several of the newer nonsteroidal anti-inflammatory drugs that block synthesis of prostaglandins. This interaction has not been reported for either aspirin or acetaminophen. All neuroleptics tested to date, with the possible exception of clozapine and the newer atypical antipsychotics, may produce more severe extrapyramidal syndromes when combined with lithium. 

Mammals have two isozymes of prostaglandin H2 synthase, COX-1 and COX-2. These have different functions but closely similar amino acid sequences (60% to 65% sequence identity) and similar reaction mechanisms at both of their catalytic centers. COX-1 is responsible for the synthesis of the prostaglandins that regulate the secretion of gastric mucin, and COX-2 for the prostaglandins that mediate inflammation, pain, and fever. Aspirin inhibits both isozymes about equally, so a dose sufficient to reduce inflammation also risks stomach irritation. Much research is aimed at developing new NSAIDs that inhibit COX-2 specifically, and several such drugs have become available. 

Engstrom K, Wallin R, Saldeen T. Effect of low-dose aspirin in combination with stable fish oil on whole blood production of eicosanoids. Prostaglandins Leukot Essent Fatty Acids 2001 64(6) 291-7. 

Aspirin, prostaglandin, and hypercalcemia Certain solid tumors (renal cell carcinoma) cause hypercalcemia, which may be mediated by prostaglandin E2. Taking a high dose of aspirin or another nonsteroidal anti-inflammatory agent will lower the serum-calcium level. 

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS ASPIRIN t risk of renal impairment. 1 efficacy of captopril and enalapril with high-dose (>100mg/day) aspirin Aspirin and NSAIDs can cause elevation of BP. Prostaglandin inhibition leads to sodium and water retention and poor renal function in those with impaired renal blood flow Monitor renal function every 3-6 months watch for poor response to ACE inhibitors when >100mg/day aspirin is given... 

The main side or adverse effect of aspirin is to cause stomach bleeding, especially when taken in large doses or repeatedly. The reason for this is related to the way in which aspirin acts to reduce pain, stopping the production of substances in the body called prostaglandins. 

Aspirin reduces the production of prostaglandins. It inhibits an enzyme involved in their synthesis called COX-i this is how it acts to reduce pain and inflammation. Therefore aspirin causes changes that increase the likelihood that the acid wiU damage the lining of the stomach. Furthermore aspirin is an acid itself, and may also contribute to the natural acidity. If repeated doses of aspirin are taken, the result can be bleeding and ulceration which may be severe in some patients. Therefore aspirin should always be taken with food. 

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