Browsing Pathways

Benzthiazide is a diuretic that acts by promoting water loss from the body. This drug is used in the treatment of hypertension and edema. They act on the kidneys by inhibiting the sodium-chloride reabsorption (via the Na+/Cl- cotransporter) from its early distal tubules. This inhibition of the cotransporter results in the increased excretion of sodium, chloride, and, in consequence, water. At the same time, it inhibits sodium transport across the renal tubular epithelium (by binding the Na+/Cl- cotransporter). In consequence, this will increase potassium excretion via the sodium-potassium exchange mechanism. The exact name of the inhibited transporter is the solute carrier family 12 member 3. The antihypertensive function of the drug is not well defined, but it is thought to act by the drug inhibition on the carbonic anhydrase or on the large-conductance calcium-activated potassium (kCa) channel, in the smooth muscles. An overdose of benzthiazide would result in symptoms like nausea, vomiting, drowsiness, and urinary problems. This drug is administered as an oral tablet.

Bepotastine is an ophthalmic H1 antagonist used to treat itchiness associated with allergic conjunctivitis. 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. Bepotastine 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.

Bepotastine is a second-generation piperidine 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.