Pathways

Chloropyramine 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.

Chloroquine is an antimalarial drug used to treat susceptible infections with P. vivax, P. malariae, P. ovale, and P. falciparum. It is also used for second line treatment for rheumatoid arthritis. Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme in Plasmodium species, preventing the conversion of heme to hemazoin. Plasmodium species continue to accumulate toxic heme, killing the parasite. Chloroquine passively diffuses through cell membranes and into endosomes, lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the organelle and raising the surrounding pH. The raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell.

Chlorothiazide is an oral diuretic drug which acts in the kidney, specifically in the distal convoluted tubule of the nephron. It is used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. In the distal convoluted tubule (DCT), the regulation of ions such as sodium, potassium, calcium, chloride and magnesium occurs. In epithelial cells of the DCT, the basolateral membrane consists of the Na+/K+ ATPase, which pumps Na+ into the interstitium-blood area and K+ into the epithelial cell; the Na+/Ca2+ exchanger, which pumps Na+ into the cell and Ca2+ into the interstitium-blood; and the chloride transporter which transports chloride into the interstitium-blood. The apical membrane contains a calcium channel that transports calcium from the lumen into the epithelial cell, a potassium channel that transports K+ out of the epithelial cell, and a Na+/Cl- cotransporter which transports Na+ and Cl- into the epithelial cell. Chlorothiazide targets this Na+/Cl- cotransporter. Chlorothiazide is transported from the blood into the epithelial cells, then is transported into the urine through the multidrug-resistant associated protein-4. In the lumen it has access to the Na+/Cl- transporter and inhibits it preventing Na+ reabsorption. The inhibition of Na+ reabsorption results in a low cytosolic concentration of Na+ and increases the solute concentration of the lumen. This decreases the lumen-epithelial cell concentration gradient and as a result, less water would be reabsorbed from the urine. This effect is valued in conditions such as hypertension because it allows more water to be excreted in urine rather than be absorbed in the blood which increases blood volume. Side effects such as frequent urination, muscle spasms, blurred vision, constipation, diarrhea, vomiting, loss of appetite, and headache can occur from taking chlorothiazide. This drug is administered as an oral tablet or as an intravenous injection.

Chlorothiazide (also known as Diuril) is an organic compound that used for diuretic. It can inhibit the solute carrier family 12 member 3 (also known as sodium-chloride symporter) in the nephron to prevent water reabsorption. Solute carrier family 12 member 3 is also used for sodium reabsorption that count for 5% of total amount. Solute carrier family 12 member 3 transports chloride and sodium from lumen to epithelial cell, and sodium/potassium ATPases facilitate the export of sodium to basolateral interstitium to provide sodium gradient that will increase the osmolarity in interstitium, which lead to establishment of osmotic gradient for water reabsorption.

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

Chlorphenamine (chlorpheniramine) is a first-generation alkylamine 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.