Browsing Pathways

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.

Didanosine (ddl) can be metabolized into dideoxyadenosine triphosphate (ddATP) by series of reaction. Dideoxyadenosine triphosphate can bind and inhibit HIV reverse transcriptase enzyme competitively against natural dATP. Dideoxyadenosine triphosphate will terminate the viral DNA chain to make it missing 3'-OH group so that formation of 5' to 3' phosphodiester could be prevented, which 5' to 3' phosphodiester is required for DNA chain elongation and result in terminated DNA growth.

Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell. Didanosine is converted into didanosine monophosphate by 5’-nucleotidase. Adenylosuccinate synthase & lyase then converts didanosine monophosphate into Dideoxyadenosine monophosphate. Dideoxyadenosine monophosphate is the converted into Dideoxyadenosine diphosphate then Dideoxyadenosine triphosphate using the enzyme adenylate kinase. Dideoxyadenosine triphosphate is an analog of deoxyadenosine triphosphate (dATP). Dideoxyadenosine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dATP and by incorporation into viral DNA. Dideoxyadenosine triphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once it gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed. Common adverse reactions include peripheral neuropathy, pancreatitis, portal hypertension, lactic acidosis, hepatitis, optical neuritis, hepatomegaly with steatosis, hyperglycemia, development of diabetes mellitus, hyperuricemia, depression, restlessness, anxiety