Pathways

Metabolites of Ioxitalamic acid are predicted with biotransformer.

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

Ipratropium is an anticholinergic drug used to control and prevent symptoms of chronic obstructive pulmonary disease (COPD) such as wheezing and shortness of breath. It can also be used for asthma or any pulmonary disease that can be relieved by opening of the bronchial airway. It is inhaled where it can immediately enter the lungs and act on the smooth muscles. Ipratropium inhibits the M1, M2, and M3 muscarinic acetylcholine receptors. These receptors are coupled to the Gq cascade which is being prevented by Ipratropium. The inhibition of the Gq cascade prevents the acitvation of phospholipase C, which would convert Phosphatidylinositol (3,4,5)-trisphosphate to inositol (3,4,5)-trisphosphate (IP3) and diacylglycerol (DAG). IP3 would then activate IP3 receptors on the sarcoplasmic reticulum leading to the release of stored calcium into the cytosol. the muscarinic acetylcholine receptors being inhibited prevents calcium from entering the cell which means calcium does not readily bind to calmodulin, and calmodulin isn't present to activate myosin light chain kinase. Since myosine light chain kinase is not activated, Serine/threonine-protein phosphatase continues to dephosphorylate myosin LC-P, and more cannot be synthesized so myosin remains unbound from actin causing muscle relaxation. This relaxation of the smooth muscles in the lungs causes the bronchial airways to relax which causes bronchodialation, making it easier to breathe.

Ipratropium is taken through inhalation into the lungs. In the lungs it will act topically and then be absorbed into the blood using the transporter solute carrier family 22 member 4 which is highly present in the bronchials. Some will be exhaled as well as some swallowed into the gastrointestinal tract for digestion. Ipratropium in the blood will majorly pass by the liver, but a small amount enters the liver through a drug transporter such as solute carrier family 22 member 4. In the endoplasmic reticulum of the liver Ipratropium is broken down into matabolites. It makes N-isopropylnortropium methobromide, N-isopropylnortropine-ester methobromide and Phenylacetic acid, and N-isopropylnortropium bromide from unknown Cytochrome P450 enzymes. These metabolites leave the liver through a transporter like Multidrug resistance-associated protein 1 into the blood where they will travel to the kidneys, or it is transported into the bile where it travels to the intestines. 80-100% is excreted renally when inhaled. The majority is excreted as unchanged Ipratropium.

Irbesaran is largely metabolized by glucuronidation and oxidation in the liver.The majority of metabolism occurs through the action of CYP2C9 with a negligible contribution from CYP3A4. Some hydroxylation also occurs in irbesartan metabolism. Irbesartan can be glucuronidated by UGT1A3 to the M8 metabolite, oxidized to the M3 metabolite, or hydroxylated by CYP2C9 to one of the M4, M5, or M7 metabolites.The M4, M5, and M7 metabolites are all hydroxylated to become the M1 metabolite, which is then oxidized to the M2 metabolite. The M4 metabolite can also be oxidized to the M6 metabolite before hydroxylation to the M2 metabolite. Finally, the minor metabolite SR 49498 is generated from irbesartan by an unknown mechanism. (DrugBank)

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.