Pathways

Torasemide is a loop diuretic drug, administered orally or intravenously to treat hypertension and edema associated with heart failure, renal failure, or liver disease. It targets the nephrons of the kidney, mainly the ascending limb of the loop of henle. The basolateral membrane of the ascending loop of henle contains the Na+/K+ ATPase, Cl- channel and K+/Cl- co-transporter which are essential for the function for ion and water reabsorption. The Na+/K+ ATPase pumps Na+ from the cell into the peritubular fluid and K+ from the peritubular fluid into the cell. The K+/Cl- co-transporter moves K+ and Cl- from the cell into the peritubular fluid and the Cl- channel transports Cl- from the cell into the peritubular fluid. The apical membrane contains the Na+/K+/2Cl- co-transporter (NKCC2) and the K+ channel. The NCKCC2 is responsible for reabsorption Na+, K+ and Cl- from the lumen into the cells of the loop of henle. The K+ channel transports K+ from the cells back into the lumen. Torasemide is transported from the capillaries into the cells of the loop of henle then transported from the cell into the lumen. Torasemide binds to NKCC2 transporter and inhibits it, preventing Na+, K+ and Cl- reabsorption from the lumen. The concentration of these ions builds up in the lumen, decreasing the slope of the concentration gradient between the cells and the lumen. Since water reabsorption is linked to ion reabsorption, water reabsorption is also decreased, resulting in a greater volume of water being excreted in urine. This is relieves symptoms such as swelling/ edema in patients. Side effects frequent urination, headache, cough, sore throat, hearing loss, ringing in your ears, upset stomach, constipation, diarrhea, weakness and excessive thirst may occur when taking torasemide.

Metabolites of Torasemide are predicted with biotransformer.

Torsemide, also known as torasemide is a pharmacologically-active small molecule that belongs to the drug class of loop diuretics. It is commonly used to manage hypertension and edema in cases of congestive heart failure as it acts as a diuretic by blocking sodium transporters NKCC2 on the thick ascending limb of the Loop of Henle in the renal tissues. Specifically it acts on solute carrier family 12 member 1. This prevents the reuptake of sodium into the Loop of Henle which consequentially reduces the uptake of water and serves to both increase water loss and reduce blood pressure. Torsemide appears to reduce blood pressure beyond its action in reducing salt uptake in the Loop of Henle; it also seems to be involved in reducing vasoconstriction by blocking the action of angiotensin II.

Terpenoids, also known as isoprenoids, are a large class of natural products consisting of isoprene (C5) units. There are two biosynthetic pathways, the mevalonate pathway and the non-mevalonate pathway or the MEP/DOXP pathway, for the terpenoid building blocks: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The action of prenyltransferases then generates higher-order building blocks: geranyl diphosphate (GPP), farsenyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP), which are the precursors of monoterpenoids (C10), sesquiterpenoids (C15), and diterpenoids (C20), respectively. Condensation of these building blocks gives rise to the precursors of sterols (C30) and carotenoids (C40). The MEP/DOXP pathway is absent in higher animals and fungi, but in green plants, the MEP/DOXP and mevalonate pathways co-exist in separate cellular compartments. The MEP/DOXP pathway, operating in the plastids, is responsible for the formation of essential oil monoterpenes and linalyl acetate, some sesquiterpenes, diterpenes, and carotenoids and phytol. However, the mevalonate pathway is absent in this organism.

Thrombopoietin (TPO) is the cytokine that is chiefly responsible for megakaryocyte production but increasingly attention has turned to its role in maintaining hematopoietic stem cells (HSCs). HSCs are required to initiate the production of all mature hematopoietic cells, but this differentiation needs to be balanced against self-renewal and quiescence to maintain the stem cell pool throughout life. TPO has been shown to support HSC quiescence during adult hematopoiesis, with the loss of TPO signaling associated with bone marrow failure and thrombocytopenia. The binding of TPO to its receptor, c-Mpl, promotes the phosphorylation of cytoplasmic signaling proteins and activation of a number of cascades that control cellular proliferation, megakaryocyte development, and survival. Suppressors of cytokine signaling (SOCS), phosphatases, and other proteins, such as focal adhesion kinase and members of the Src family kinases can suppress TPO signaling.

Trabectedin is an antineoplastic from the alkylating agent drug class. It is derived from a marine-derived antitumor molecule discovered in the Caribbean tunicate Ecteinascidia turbinata. This drug is indicated in the treatment of advanced soft tissue sarcoma (liposarcoma or leiomyosarcoma) in Europe, Russia, and South Korea. It is also approved as an orphan drug by the FDA for the treatment of soft tissue sarcomas and ovarian cancer. Trabectedin binds covalently to the DNA minor groove. This molecule binds and alkylates guanine bases to the N2 position with its two rings in its structure, causing the equivalent of a functional interstrand crosslink. The third ring protrudes from the DNA strand which lets it interact with nearby nuclear proteins. It affects various transcription factors involved in cell proliferation via the transcription-coupled nucleotide excision repair system (NER). With this mechanism of action, trabectedin blocks the cell cycle at the G2 phase, resulting in the apoptosis of the cancerous cell, This drug is administered as an intravenous injection.

Tramadol is an analgesic drug consisting of two enantiomer forms (+)-Tramadol and (-)-Tramadol. Both contribute to pain relief by inhibiting pain transmission in the spinal cord via different mechanisms. (+)-Tramadol is a selective agonist of the mu receptor (OP3) inhibiting serotonin reuptake, while (-)-Tramadol inhibits norepinephrine reuptake in the central nervous system. Although tramadol is structurally related to codeine and morphine, it’s affinity for the mu receptor compared to other opioids is significantly less. Therefore tramadol is used when treatment with strong opioids is not necessary since it’s pharmacodynamic and pharmacokinetic properties suggest the low likelihood of patients becoming dependent.