Pathways

Candicidin is a polyene antifungal antibiotic produced by a strain of Streptomyces griseus. It is especially effective against Candida albicans (more effective than amphotericin B), and is administered intravaginally in the treatment of vulvovaginal candidiasis. Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of Candicidin. Candicidin binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.

Metabolites of Candesartan cilexetil are predicted with biotransformer.

This drug is administered as the prodrug (candesartan cilexetil), this molecule is quickly converted in candesartan, the active metabolite while it is absorbed in the gastrointestinal tract (ester hydrolosis). Candesartan selectively inhibits the binding of angiotensin II to Type-1 angiotensin II receptors (AT1) in vascular smooth muscle and adrenal glands. In consequence of this interaction, AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II are inhibited (inhibition of the RAAS). The last inhibition may increase sodium and water excretion while decresing the excretion of potassium. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin comes in the blood by the granular cells (kidneys). This protein cleaves the angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing sodium and water reabsorption in the kidneys via aldosterone secretion. Angiotensin II can bind two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). AT1, a G-protein coupled receptor, mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Candesartan cilexetil is available as a tablet.

Candesartan 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. Candesartan is used to treat hypertension as it reduces blood pressure. 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 candesartan contribute to an overall lowered blood pressure. The most common side effects of taking candesartan are symptomatic hypotension, abnormal renal function, and hyperkalemia. Other reported side effects include headache, back pain, angioedema, and upper respiratory tract infections, but these are very rare clinically.

Candesartan (also named Blopress or Atacand) is an active metabolite of angiotensin II receptor blockers (ARBs) pro drug, candesartan cilexetil. Candesartan cilexetil converts to candesartan rapidly in gastrointestinal tract during absorption. Candesartan 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 candesartan 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 or triamterene pathways, which describes the mechanism of direct aldosterone antagonists. Candesartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.

The hallmarks of cancer, the Warburg review