Pathways

Raltitrexed is a folate analog that is used in the treatment of colorectal cancer, that is an inhibitor of thymidylate synthase. Inhibiting thymidylate synthase stops the proliferation of cancer cells, as it stops the production and formation of purines and pyrimidines needed for DNA replication. Once transported into the cells through a reduced folate carrier it is polyglutamated by folylpolyglutamate synthetase to further enhance the inhibitory action. There are some side effects that may occur such as pale skin, trouble breathing, bleeding, bruising, fatigue, chest pains, chills, cough, fever and issues with gastrointestinal issues.

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

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor for the conversion of angiotensin I into angiotensin II. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Ramipril is used to treat hypertension, high blood pressure, congestive heart failure, and chronic renal failure as it decreases blood pressure. Ramipril is converted into Ramiprilat through the liver after being ingested which travels in the blood to inhibit ACE which is from the lungs. Angiotensin has many vasoconstrictive effects by binding to angiotensin II type 1 receptor (AT1) in blood vessels, kidneys, hypothalamus, and posterior pituitary. In blood vessels, AT1 receptors cause vasoconstriction in the tunica media layer of smooth muscle surrounding blood vessels increasing blood pressure. Less angiotensin II that is circulating lowers the constriction of these blood vessels. AT1 receptors in the kidney are responsible for the production of aldosterone which increases salt and water retention which increases blood volume. Less angiotensin II reduces aldosterone production allowing water retention to not increase. AT1 receptors in the hypothalamus are on astrocytes which inhibit the excitatory amino acid transporter 3 from up-taking glutamate back into astrocytes. Glutamate is responsible for the activation of NMDA receptors on paraventricular nucleus neurons (PVN neurons) that lead to thirst sensation. Since angiotensin II levels are lowered, the inhibition of the uptake transporter is not limited decreasing the amount of glutamate activating NMDA on PVN neurons that make the individual crave drinking less. This lowers the blood volume as well. Lastly, the AT1 receptors on posterior pituitary gland are responsible for the release of vasopressin. Vasopressin is an anti-diuretic hormone that cases water reabsorption in the kidney as well as causing smooth muscle contraction in blood vessels increasing blood pressure. Less angiotensin II activating vasopressin release inhibits blood pressure from increasing. Overall, Ramipril inhibits the conversion of angiotensin I into angiotensin II, a powerful vasoconstrictor and mediator of high blood pressure so decreasing levels of angiotensin will help reduce blood pressure from climbing in individuals.

Ramipril (trade name: Altace) belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Ramipril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form ramiprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.

Ramipril (trade name: Altace) belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Ramipril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form ramiprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.

Ramucirumab serves as an antineoplastic agent and direct antagonist of VEGFR2 (vascular endothelial growth factor receptor 2), counteracting the binding of natural VEGF ligands secreted by solid tumors. This action inhibits angiogenesis and the enhancement of tumor blood supply, pivotal processes for cancer progression. It is a human monoclonal antibody (IgG1) designed against VEGFR2, a transmembrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab disrupts the binding of ligands (VEGF-A, VEGF-C, and VEGF-D), thereby impeding receptor phosphorylation and downstream cellular responses like proliferation, permeability, and migration of endothelial cells. Since VEGFR stimulation plays a crucial role in angiogenesis and cancer progression, ramucirumab's targeted interference is highly significant. Notably, it binds to a specific epitope on the extracellular domain of VEGFR-2, blocking all VEGF ligands from binding. Ramucirumab finds application in the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma, metastatic non-small cell lung cancer with specific genomic mutations, metastatic colorectal cancer, and hepatocellular carcinoma, often in combination with other therapies.

Ranitidine is an anti-ulcer agent, that works through antagonizing the histamine H2 receptor. It is used to reduce abdominal pain, heartburn, acid indigestion and acid reflux. The pathway begins in the stomach, where ranitidine inhibits the histamine H2 receptor on the surface of the parietal cell. Now in the gastric endothelial cell, potassium-transporting ATPase units are inhibited by G-Protein signalling cascade through somatostatin receptor type 4, which is activated by somatostatin. At the same time, potassium-transporting ATPase is activated by the G-protein signalling cascade, through histamine H2 receptor which is inhibited by ranitidine, gastrin/cholecystokinin type B receptor, and muscarinic acetylcholine receptor M3 which are activated by histamine, gastrin and acetylcholine, respectively. The potassium transporting ATPase also converts water and ATP to a phosphate molecule and ADP. Alongside the transporters, potassium is brought into the cell. Carbonic anhydrase 1 uses water and carbon dioxide to create hydrogen carbonate and a hydrogen ion, which are both transported out of the endothelial cell, into the gastric lumen. A chloride ion is transported into the gastric endothelial cell through a chloride anion exchanger and is transported out of the cell through a chloride intracellular channel protein 2, back into the gastric lumen.