Pathways

Isosorbide mononitrate is an organic nitrate and an antianginal drug used to treat Angina Pectoris through vasodilation. It is an active metabolite of isosorbide dinitrate. As a organic nitrate, it is a prodrug for nitric oxide, which is a gas that is a potent vasodilator. Isosorbide works on arteries and veins, but predominately acts on veins to reduce cardiac preload. It has a longer duration of action compared to nitroglycerin. Isosorbide mononitrate enters the smooth muscle cell or myocyte through an unknown transporter. It is then metabolized in the cytosol into nitric oxide by P450 enzymes, xanthine oxidoreductase (XO), glutathione-S-transferase (GST), or cytosolic aldehyde dehydrogenase isoforms. Nitric oxide activates Guanylate cyclase which catalyzes GTP into cGMP. cGMP activates cGMP-dependent protein kinase. Activated protein kinase has many interactions within the myocyte. Protein kinase activates potassium channels which causes potassium to leave the myocyte. This causes hyperpolarization in the cell. This prevents the voltage-gated calcium channels from opening and allowing calcium into the cell. This is also prevented by protein kinase inhibiting the voltage-gated calcium channels. This along with the activation of calcium pumps out of the cell and into the sarcoplasmic reticulum causes the cytosolic concentration of calcium to be very low. Low concentrations of calcium cannot bind to calmodulin which means calmodulin cannot activate myosin light chain kinase. With myosin light chain kinase unable to activate, myosin light chain cannot be phosphorylated which means that it is dephosphorylated by myosin light chain phosphatase. The accumulation of myosin light chain causes myosin to unbind from actin and the muscle to relax. The relaxation of smooth muscles around blood vessels causes vasodilation. This leads to the effects of decreased cardiac oxygen consumption, redistribution coronary flow toward ischemic areas via collaterals, and the relief of coronary spasms.

Metabolites of Isosulfan blue are predicted with biotransformer.

Isothipendyl is a first-generation H1-antihistamine. 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. Isothipendyl 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.

Isothipendyl is a first-generation phenothiazine H1-antihistamine. 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.

Isothipendyl is a first-generation H1-antihistamine. 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. Clemastine 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.

Isothipendyl is a first-generation H1-antihistamine. 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.

Isovaleric academia, also called IVA, is an extremely rare inherited inborn error of metabolism (IEM) of leucine metabolism. It is an autosomal recessive disorder that is caused by a deficiency of isovaleryl-CoA dehydrogenase. It is characterized by a build-up of isovaleric acid in the blood and other biofluids. High levels of isovaleric acid lead to a rancid cheese odour. There are two major phenotypes of IVA: (1) an acute form and (2) a late-onset form. The acute form manifests as catastrophic disease in the newborn period and infants become extremely sick in the first week of life. There is usually a history of poor feeding, vomiting, lethargy, and seizures. In the acute form, metabolic acidosis is present, usually with an elevated anion gap and ketosis. There may be secondary hyperammonemia, thrombocytopenia, neutropenia, and sometimes anemia. The late-onset form is characterized by chronic, intermittent episodes of metabolic decompensation. The degree of isovaleryl-CoA dehydrogenase deficiency and the mutations differ between the two extreme presentations. The acute form of IVA is reasonably treatable. Administration of glycine has been shown to reduce isovaleric acidemia in neonates. Glycine is readily conjugated with isovaleric acid, which leads to urinary excretion of the conjugate. A diet that is also restricted in leucine consumption is also useful in treating the disorder.