Pathways

Metabolites of Carteolol are predicted with biotransformer.

Carvedilol, trade name Coreg, is a nonselective beta-blocker that blocks both alpha and beta receptors of the heart and blood vessels. It is prescribed to treat hypertension, stable angina pectoris and congestive heart failure. Carvedilol also blocks calcium channels. Its activity decreases heart rate, myocardial contractility and oxygen demand and decreases vascular resistance. It also posses a unique feature for a beta-blocker, it has an anti-free-radical effect. This effect may prevent free radical damage to treat chronic heart failure.

Carvedilol is a cardio non-selective beta blocker. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. Carvedilol is a racemic mixture where the S(-) enantiomer is a beta adrenoceptor blocker and the R(+) enantiomer is both a beta and alpha-1 adrenoceptor blocker. In bronchial and vascular smooth muscle, carvedilol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, carvedilol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like carvedilol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Carvedilol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.

Carvedilol can be hydroxlated at the 1 position by CYP2D6, CYP1A2, or CYP1A1 to form 1-hydroxypheylcarvedilol; at the 4 position by CYP2D6, CYP2E1, CYP2C9, or CYP3A4 to form 4'-hydroxyphenylcarvedilol; at the 5 position by CYP2D6, CYP2C9, or CYP3A4 to form 5'-hydroxyphenylcarvedilol; and at the 8 position by CYP1A2, CYP3A4, and CYP1A1 to form 8-hydroxycarbazolylcarvedilol. Carvedilol can also be demethylated by CYP2C9, CYP2D6, CYP1A2, or CYP2E1 to form O-desmethylcarvedilol. Carvedilol and its metabolites may undergo further sulfate conjugation or glucuronidation before elimination. Carvedilol can be O-glucuronidated by UGT1A1, UGT2B4, and UGT2B7 to form carvedilol glucuronide. (DrugBank) Reactions associated with Carvedilol are attached as a sub-pathway (Carvedilol Metabolic pathway - Part 2)

Carvedilol can be hydroxlated at the 1 position by CYP2D6, CYP1A2, or CYP1A1 to form 1-hydroxypheylcarvedilol; at the 4 position by CYP2D6, CYP2E1, CYP2C9, or CYP3A4 to form 4'-hydroxyphenylcarvedilol; at the 5 position by CYP2D6, CYP2C9, or CYP3A4 to form 5'-hydroxyphenylcarvedilol; and at the 8 position by CYP1A2, CYP3A4, and CYP1A1 to form 8-hydroxycarbazolylcarvedilol. Carvedilol can also be demethylated by CYP2C9, CYP2D6, CYP1A2, or CYP2E1 to form O-desmethylcarvedilol. Carvedilol and its metabolites may undergo further sulfate conjugation or glucuronidation before elimination. Carvedilol can be O-glucuronidated by UGT1A1, UGT2B4, and UGT2B7 to form carvedilol glucuronide. (DrugBank) Reactions associated with Carvedilol are attached as a sub-pathway (Carvedilol Metabolic pathway - Part 1)

Caspofungin is an echinocandin antifungal drug used to treat a variety of fungal infections. It is known as the brand Cancidas. It is used for the treatment of esophageal candidiasis and invasive aspergillosis in patients who are refractory to or intolerant of other therapies.It works by inhibiting cell wall synthesis. Caspofungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This prevents the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, which ultimately leads to osmotic instability and cell death.

Castor Oil is a prostaglandin E1 analog that reduces the risk of NSAID-induced gastric ulcers. Castor Oil stimulates prostaglandin receptors on parietal cells in the stomach to reduce gastric acid secretion. Castor Oil activates prostaglandin EP3 receptors in parietal cells. Activation of this receptor triggers the Gi protein signaling cascade, inhibiting adenylate cyclase. Adenylate cyclase is responsible for converting ATP to cAMP, therefore, inhibition of adenylate cyclase reduces cytosolic cAMP concentration. cAMP is responsible for activating protein kinase A. With lower concentrations of cAMP, less protein kinase A is activated. Protein kinase A activates the proton pump in the luminal membrane of the parietal cell. The role of the proton pump is to secrete acid (H+) into the stomach lumen. With reduced protein kinase A activation, this decreases the activity of the proton pump, fewer H+ ions are pumped into the lumen, reducing the acidity and thus allowing stomach ulcers to heal and reducing the pain caused by the ulcers. Castor Oil may also promote ulcer healing by increasing mucus and bicarbonate secretion and thickening the mucosal bilayer so the mucosa can generate new cells.