The authors say, "Experimental studies have suggested a rebound effect after aspirin discontinuation, involving increased thromboxane
levels possibly resulting from the pro-thrombotic effects of residual very low levels of aspirin." Does a rebound effect increase heart attack risk, even if a patient discontinues aspirin therapy for a short time because of surgery or other medical procedure?
Cyclooxygenases (COX) catalyze the production of prostaglandins and thromboxanes
from arachidonic acid as depicted in Figure 4 .
(1) Prostanoids include what are sometimes referred to as the "classical" prostaglandins (PGs), such as PGD, PGE, and PGF (all of which have a prostanoic acid backbone), as well as prostacyclin ([PGI.sub.2]) and thromboxane
. Specific prostanoids are designated by a letter that indicates the type of ring structure, followed by a number that indicates the number of double bonds in the hydrocarbon structure.
synthase (TXS) is a hemoprotein with feature of the cytochrome P-450 family which catalyzes prostaglandin endoperoxide into thromboxanes
Phipps, "Human bone marrow megakaryocytes and platelets express PPARy, and PPARy agonists blunt platelet release of CD40 ligand and thromboxanes
," Blood, vol.
(11) The aspirin-induced decrease in thromboxane
production leads to a decline in platelet activation and aggregation, which accounts both for aspirin's beneficial cardiovascular effects and the associated risk of bleeding--aspirin's most common adverse effect.
Prostacyclin opposes the effects of thromboxane
, a thrombogenic and atherogenic eicosanoid.
Both NSAIDs and COX-2s work by inhibiting the enzyme cyclo-oxygenase (COX) which in turn stops the production of prostaglandins (PGE2 and PGF2[alpha]) and thromboxanes
from membrane phospholipids.
To the Editor: Chin and Commerford (1) suggest the imbalance between eicosanoids (prostacyclins and thromboxanes
) as a possible cause for the observed increase in cardiovascular risk with the cyclo-oxygenase-2 (COX-2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs).
BERLIN -- A new type of NSAID that inhibits the production of leukotrienes, prostaglandins, and thromboxanes
was as effective as and better tolerated than a standard NSAID or a selective cyclooxygenase inhibitor for the treatment of osteoarthritis in a pair of phase III studies.
Licofelone also inhibits both cydooxygenase (COX)-1 and COX-2, the enzymes that convert arachidonic acid into prostaglandins and thromboxanes
, which means that the drug is a dual LOX-COX inhibitor.
(58,63) This process leads to an increase in circulating tissue levels of various cytokines, (177-180) leukotrienes, (181) thromboxanes
, (182) platelet activating factor, (183) complement components, (184) elastases, and other enzymes, (185) and it causes the formation of additional ROS.