Pathways

Irbesartan (also named Avapro) is an antagonist of angiotensin II receptor blockers (ARBs). Irbesartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of irbesartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Irbesartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.

Irbesartan is angiotensin receptor blocker (ARB) which block the action of angiotensin II by binding to the type 1 angiotensin II receptor. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Irbesartan is used to treat hypertension, delay progression of diabetic nephropathy, and treat congestive heart failure. Angiotensin has many vasoconstrictive effects by binding to angiotensin II type 1 receptors (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. Blocking this AT1 receptor 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. Blocking AT1 receptors 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 AT1 receptors are blocked, the inhibition of the uptake transporter is not limited decreasing the amount of glutamate activating NMDA on PVN neurons that makes 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. Lowering angiotensin II action on activating vasopressin release inhibits blood pressure from increasing. All these effects of irbesartan contribute to an overall lowered blood pressure.

Metabolites of Irbesartan are predicted with biotransformer.

Irinotecan is a medication commonly sold as Camptosar, used to stop the growth of cancer cells, and to stop the spread of cancer cells in the human body. Specifically cancers of the rectum and of the colon. Commonly used in combination with chemotherapy. Irinotecan works through its active metabolite, SN-38, which inhibits the action of topoisomerase I. This enzyme is responsible for creating single-strand breaks in DNA during replication. These single-strands are reversible. SN-38 and Irinotecan binding to topoisomerase I-DNA complex results in the prevention of religation the DNA strand mentioned above, which creates double-strand DNA breakage. This breakage leads to cell death. Irinotecan is taken orally, but can also be injected.

Irinotecan, branded as Camptosar, Campto, Onivyde and others, is a cancer medication used to treat colon and small cell lung cancers, alone or with other drugs. Irinotecan can be processed by the cytochrome P450 3A4 enzyme, producing both the side product glutaral, as well as a compound called NPC. the NPC can then be catalyzed by liver carboxylesterase 1 to form 7-ethyl-10-hydroxy-camptothecin, or SN-38. Alternatively, irinotecan can directly form SN-38 via catalysis by liver carboxylesterase 1. After its formation, SN-38 is converted to SN-38 glucuronide by UDP-glucuronosyltransferase 2B11. This can then be converted back to SN-38 in the lysosome by beta-glucuronidase, or can be excreted as the end product of the pathway.