Pathways

Diclofenac is an NSAID used to treat the signs and symptoms of osteoarthritis and rheumatoid arthritis. Diclofenac possesses anti-inflammatory, analgesic, and antipyretic activity. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme that is responsible for prostaglandin synthesis during inflammation. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Diclofenac inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Inflammatory and infectious diseases trigger fever. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because diclofenac decreases PGE2 in the CNS, it has an antipyretic effect. Antipyretic effects increase peripheral blood flow, vasodilation, and subsequent heat dissipation. It is administered in many different ways: as a topical ointment/cream/gel/patch, as an oral tablet/capsule, as an ophthalmic solution, and as a rectal suppository.

Metabolites of Diclofenac are predicted with biotransformer.

Dicloxacillin is an Dicloxacillin is an oral, second generation penicillin antibiotic that is used to treat bacterial infections caused by penicillinase-resistant staphylococci. Dicloxacillin is a beta-lactamase resistant penicillin similar to oxacillin. Dicloxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. Dicloxacillin exerts a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. It inhibits the biosynthesis of the bacterial cell wall. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, dicloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that dicloxacillin interferes with an autolysin inhibitor.

Metabolites of Dicloxacillin are predicted with biotransformer.

Dicomarol is an anticoagulant agent that antagonizes the metabolism of vitamin K, by doing so inhibits the function of clotting factors within the body. It appears to target prothrombin, and coagulation factors VII, IX and X. Mainly inhibiting vitamin K reductase, which reduces vitamin K so that it can be used as the cofactor for future reactions. This is commonly used to decrease blood clotting in patients who suffer from deep vein thrombosis which is local cogulation within the circulatory system that can lead to infarction and or a stroke. Dicomarol originates from sweet clover and is often administered through oral ingestion. Try avoiding herbs and supplements that could interfere with anticoagulant activity such as ginseng, ginkgo, ginger and garlic.

Dicumarol or dicoumarol is a vitamin K antagonist derived from sweet-clover hay in the 1940s. It was discovered as the cause of a bleeding disease in cattle that ingested it, and was then used to treat blood clots. Dicumarol is the drug that warfarin was based on. The drug works as other vitamin K antagonists, by reducing the stores of reduced vitamin K, by inhibiting the vitamin K reductase complex, and preventing the recycling of the vitamin K within the cell. This in turn prevents coagulation factors VIII, IX, X as well as prothrombin, factor II, from activating, which in turn prevents fibrin clots from being formed and stabilized. Dicumarol is administered orally, and within 2 days, it is absorbed in the intestine and enters the liver. There, it inhibits the vitamin K epoxide reductase complex, preventing vitamin K1 2,3-epoxide from being recycled into reduced vitamin K. This leads to less reduced vitamin K to be present in order to react with the precursors of coagulation factors II, VII, IX and X through the vitamin K dependent gamma-carboxylase, and prevents those coagulation factors from being produced. Normally, coagulation factor IX is activated by factor XIa, which then, with the addition of coagulation factor VIII, forms the tenase complex that activates coagulation factor X. Activated coagulation factor Xa then joins with coagulation factor V to form the prothrombinase complex which forms thrombin from prothrombin. Thrombin is then necessary to convert fibrinogen to loose fibrin within the blood plasma, as well as converting coagulation factor XIII into its activated form. The fibrin then is able to polymerizes, and is stabilized into a water insoluble clot by coagulation factor XIIIa. The presence of dicumarol and the absence of reduced vitamin K prevents this coagulation cascade from occurring as much due to lack of substrates, and thus helps to prevent blood clotting.

Dicoumarol (also known as bishydroxycoumarin) is an anticoagulant that inhibit the liver enzyme vitamin K reductase, which cause Vitamin K1 2,3-epoxide could not be catalyzed by vitamin K reductase to form vitamin KH2, the reduced form of vitamin K. Vitamin K-dependent coagulation factors (II, VII, IX, and X) requires its cofactor, vitamin K to facilitate the activation and gamma-carboxylation. Inhibition of vitamin K reductase results in reduced concentration of vitamin KH2, which will ultimately lead to decreased coagulability of the blood and reduced cleavage of fibrinogen into fibrin.

Dicumarol (also known as bishydroxycoumarin) is an anticoagulant that inhibit the liver enzyme vitamin K reductase, which cause Vitamin K1 2,3-epoxide could not be catalyzed by vitamin K reductase to form vitamin KH2, the reduced form of vitamin K. Vitamin K-dependent coagulation factors (II, VII, IX, and X) requires its cofactor, vitamin K to facilitate the activation and gamma-carboxylation. Inhibition of vitamin K reductase results in reduced concentration of vitamin KH2, which will ultimately lead to decreased coagulability of the blood and reduced cleavage of fibrinogen into fibrin.