Pathways

Clodronic acid is a bisphosphonate used for the treatment of osteoporosis in women experiencing menopause, hypercalcemia malignancy and osteolysis. Travelling into the bone it binds to hydroxyapatite, osteoclast break down the bone releasing the bisphosphonate. Bisphosphonate is then consumed by the osteoclast by endocytosis and disrupts their mechanism of breaking down the bone. Usually administered intravenously, it is not metabolized and is eliminated via the urine unchanged. Caution should be taken as severe overdoses can cause kidney failure, liver damage and render the patient unconscious. It can be managed through monitoring as hypocalcemia can present itself prior to the overdose, and specializing care via the administration of electrolytes.

Clodronic acid is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Clodronic acid passes through the liver and is then excreted from the body mainly through the kidney.

Clofarabine is a purine (adenosine) antimetabolite, it is a drug used as an antineoplastic in the treatment of pediatric patients with relapsed or refractory acute lymphocytic leukemia. This molecule differs from the other purine analogs by chlorine in the purine ring and fluorine in the ribose moiety. This drug enters the cell and is metabolized to the active 5'-monophosphate metabolite by the enzyme deoxycytidine kinase. It is also metabolized in the 5'-triphosphate metabolite by mono- and di-phospho kinase. The tri-phosphate metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA elongation and inhibiting repair through competitive inhibition of DNA polymerases. Those inhibitions lead to the depletion of the intracellular deoxynucleotide triphosphate pool thereby intensifying the effectiveness of DNA synthesis inhibition. Clofarabine 5'-triphosphate also disrupts the integrity of the mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C, and apoptosis-inducing factor. All of the cited inhibitions and activities of this drug lead to cell death (apoptosis). This drug is administered as an intravenous injection.

Metabolites of Clofazimine are predicted with biotransformer.

Chlophedianol is an H1-antihistamine cough suppressant. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Clofedanol also inhibits the H1 histamine receptor on bronchiole smooth muscle myocytes. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin.Calcium bound calmodulin is required for the activation of myosin light chain kinase. This prevents the phosphorylation of myosin light chain 3, causing an accumulation of myosin light chain 3. This causes muscle relaxation, opening up the bronchioles in the lungs, making breathing easier.

Chlophedianol is an H1-antihistamine cough suppressant. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Chlophedianol inhibits the H1 histamine receptor on blood vessel endothelial cells. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin. Calcium bound calmodulin is required for the activation of the calmodulin-binding domain of nitric oxide synthase. The inhibition of nitric oxide synthesis prevents the activation of myosin light chain phosphatase. This causes an accumulation of myosin light chain-phosphate which causes the muscle to contract and the blood vessel to constrict, decreasing the swelling and fluid leakage from the blood vessels caused by allergens.

Chlophedianol is an H1-antihistamine cough suppressant. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.