Pathways

Cilazapril is an angiotensin-converting enzyme competitive inhibitor that binds to the same active site as angiotensin I. Cilazapril is a prodrug which is converted to its active form by the liver after being oral ingested, it then becomes its main metabolite Cilazaprilat. Cilazapril is used to treat hypertension and heart failure as it reduces the effects of angiotensin II which decreases resistance and blood pressure, as angiotensin II is a potent vasoconstrictor. Angiotensin II is produced by angiotensin-converting enzyme converting angiotensin I to angiotensin II. Angiotensin II acts on the kidneys, blood vessels, posterior pituitary gland and excitatory amino acid transporter via attaching to the Type-1 angiotensin II receptor. The kidney responds by increasing aldosterone secretion which is responsible for water and sodium uptake via the distal tubule and collecting duct. The posterior pituitary gland reacts by increasing vasopressin release, vasopressin acts on the collecting ducts to increase water reabsorption. Blood vessels react by vasoconstricting, and the excitatory amino acid transporter is inhibited and therefore does not take up L-glutamic acid into the astrocytes leaving them to interact with the NMDA receptors on the paraventricular nucleus neuron (PVN neuron) to elicit a thirst sensation, in order to encourage the body to drink more water. All of these effects together leads to increased blood pressure and resistance throughout the body which is detrimental to someone with hypertension or heart failure as it makes it more difficult for blood to circulate throughout the body. Cilazapril inhibits angiotensin II thus inhibiting its downstream effects as well, reducing aldosterone and vasopressin secretion, inhibiting vasoconstriction, and allowing the amino acid transporter to be activated. The amino acid transporter being activated means the astrocytes uptake L-glutamic acid, reducing its interaction with the PVN neuron and thus reduce thirst response. All of these in combination ultimately reduces blood pressure and resistance in the blood vessels, treating the patients for their increased blood pressure. Some adverse effects may include hypotension, hyperkalaemia, and hyponatraemia. This is due to the decreased blood pressure, decreased uptake of sodium and insufficient potassium excretion due to reduced aldosterone levels. Cilazapril is eliminated by the kidneys and excreted through urination.

Cilazapril (trade name: Dynorm, Inhibace, Vascace) 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. Cilazapril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form cilazaprilat 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.

Cilazapril (trade name: Dynorm, Inhibace, Vascace) 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. Cilazapril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form cilazaprilat 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.

Cilgavimab is an extended half-life recombinant monoclonal IgG1κ antibody directed against the SARS-CoV-2 spike glycoprotein for COVID-19 prophylaxis in individuals who are unable to undergo COVID-19 immunization. It is produces in Chinese hamster ovary cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions. It is commonly taken with tixagevimab, and was issued FDA emergency use authorization on December 9, 2021. SARS-CoV-2 enters host cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Cilgavimab inhibits S glycoprotein by blocking the interaction between it and the host ACE2 protein. This inhibits the binding and entry of the virion into the host cell. This prevents viral replication and propagation.

Cilostazol, also sold as Pletal, is a drug used to prevent platelet aggregation, specifically treating symptoms of intermittent claudication caused by peripheral artery disease as well as preventing strokes. Cilostazol is ingested orally, and it enters the liver, where it is metabolized in the endoplasmic reticulum by cytochrome P450 3A4 into 4-hydroxycilostazol, and by cytochrome P450 2C19 and 3A5 into 4-cis-hydroxycilostazol. Each of these metabolites is further metabolized, 4-hydroxycilostazol into 3,4-dehydrocilostazol and 4-cis-hydroxycilostazol into 4'-trans-hydroxycilostazol respectively. These two metabolites are the active metabolites, and they both act to inhibit the action of cAMP-specific 3',5'-cyclic phosphodiesterase 4D in platelets. With this enzyme inhibited, it is unable to metabolize cAMP into AMP, which leads to a buildup of cAMP in the blood. cAMP in turn is known to prevent aggregation of platelets, by inhibiting their adhesion to collagen, as well as decreasing the amount of calcium within the cytosol, preventing granule release, which then prevents activation of other platelets.

Cilostazol, industrially sold as Pletal, is a quinolone derivative antiplatelet drug and a vasodilator used to prevent platelet aggregation, specifically treating symptoms of intermittent claudication caused by peripheral artery disease as well as preventing strokes in Homo sapiens. It acts on blood cells called platelets and on the vasculature by inhibiting phosphodiesterase 3 activity which causes these platelets to stop from sticking together, preventing formation of harmful clots. Cilostazol helps the blood to move more easily and keeps blood flowing smoothly in your body. Cilostazol is ingested orally, and it enters the liver (not shown here), where it is metabolized into active metabolites that inhibit the action of cAMP-specific 3',5'-cyclic phosphodiesterase 4D which converts cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP) in platelets. Inhibition of PDE3 causes a build-up of cAMP which subsequently leads to increased concentrations of the active form of protein kinase A (PKA). PKA then converts vasodilator-stimulated phosphoprotein (VASP) into phosphorylated vasodilator-stimulated phosphoprotein (VASP-P) which in turn is known to prevent aggregation of platelets, by inhibiting their adhesion to collagen, as well as decreasing the amount of calcium within the cytosol, preventing granule release, which then prevents activation of other platelets. Usage of cilostazol relieves symptoms like claudication(cramps) and the intermittent pain it causes. Common side effects of cilostazol are headache, diarrhea, vomiting, abnormal stools, dizziness, weakness, fast or pounding heartbeats, palpitations, swelling (edema), leg cramps, numbness or tingling, joint pain, cough, runny or stuffy nose, infections.

Metabolites of Cilostazol are predicted with biotransformer.