Pathways

Sorafenib is a drug that belongs to the antineoplastics drug class, which is the drug class relating to the treatment of cancer, specifically renal, hepatic and thyroid cancers. This drug works by stopping cancerous tumour progress and stopping therapy replication pf potentially malignant cells. It does this by inhibiting protein synthesis, as we will explore in the pathway. Sorafenib is administered orally, in a tablet form taken twice daily without food. Once ingested, sorafenib finds itself in the endoplasmic reticulum membrane , where it inhibits cytochrome P450 2B6, cytochrome P450 2C8, cytochrome P450 2C9 and UDP-glucuronosyltransferase 1-1. Sorafenib is also catalyzed, with the help uridine diphosphate glucuronic acid and the enzyme UDP-glucuronosyltransferase 1-9 to sorafenib b-D-glucuronide with a by-product of uridine 5’-diphosphate. Sorafenib also undergoes a transformation without the use of catalytic enzymes and becomes sorafenib metabolite M4 and subsequently becomes sorafenib metabolite M5. In another reaction, sorafenib teams up with water and oxygen, using cytochrome P450 3A4 to create sorafenib N-oxide and hydrogen peroxide. Sorafenib N-oxide then undergoes two more reactions, one where it becomes sorafenib N-oxide glucuronide, and another where it becomes sorafenib metabolite M1. Sorafenib metabolite M1 is also attached to another reaction, as sorafenib creates sorafenib metabolite M3, sorafenib metabolite M1 is also created from this metabolite.

Sotalol is a beta-adrenergic receptor antagonist, which is a treatment regimen for heart failure such as abnormal heart rhythms. Sotalol inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium and β2-adrenergic receptors within bronchial and vascular smooth muscle. The electrophysiologic effects of sotalol may be due to its selective inhibition of the rapidly activating component of the potassium channel involved in the repolarization of cardiac cells.

Sotalol is a methane sulfonanilide beta adrenergic antagonist used to treat life-threatening ventricular arrhythmias and to maintain sinus rhythm in atrial fibrillation or flutter. After being taken orally, it is absorbed into the blood through the GI tract and inhibits the beta 1 adrenergic receptor and the potassium voltage gated channel subfamily H member 2 protein on the cell membranes of cardiomyocytes. The beta 1 adrenergic receptor is responsible for Gs signalling and the production of cyclic adenosine monophosphate (cAMP) which activates the L-type calcium channel. The L-type calcium channel is responsible for the influx of calcium from extracellular environment into the cytosol of cardiomyocytes which activates ryanodine receptors to release calcium from the sarcoplasmic reticulum. Calcium is important for the contraction of heart muscle for myosin to and actin to power-stroke so the slower influx of calcium slows down the contractions of the heart lowering the heart rate. Sotalol is a competitive inhibitor of the rapid potassium channel. This inhibition lengthens the duration of action potentials and the refractory period in the atria and ventricles. The inhibition of rapid potassium channels is increases as heart rate decreases, which is why adverse effects like torsades de points is more likely to be seen at lower heart rates. The inhibition of potassium voltage gated channel subfamily H member 2 protein inhibits the efflux of potassium out of the cell during the repolarization phase of an action potential. This lengthens the QT interval of the heartbeat as well as prolonging the repolarization phase of action potentials. This regulates the heart rate and slows down any rapid heartrates. The action of sotalol on beta adrenergic receptors lengthens the sinus node cycle, conduction time through the atrioventricular node, refractory period, and duration of action potentials. Sotalol can be found under the brand names Betapace, Sorine, and Sotylize. Some side effects of using this drug may include feeling dizzy or sick, feeling tired, having diarrhoea or a headache.

Sotalol is a potassium channel beta blocker used to treat ventricular arrhythmias and to help maintain normal sinus rhythm in atrial fibrillation and flutter. After being taken orally, it is absorbed into the blood through the GI tract and inhibits the beta 1 adrenergic receptor and the potassium voltage gated channel subfamily H member 2 protein on the cell membranes of cardiomyocytes. The beta 1 adrenergic receptor is responsible for Gs signalling and the production of cyclic adenosine monophosphate (cAMP) which activates the L-type calcium channel. The L-type calcium channel is responsible for the influx of calcium from extracellular environment into the cytosol of cardiomyocytes which activates ryanodine receptors to release calcium from the sarcoplasmic reticulum. Calcium is important for the contraction of heart muscle for myosin to and actin to power-stroke so the slower influx of calcium slows down the contractions of the heart lowering the heart rate. The inhibition of potassium voltage gated channel subfamily H member 2 protein inhibits the efflux of potassium out of the cell during the repolarization phase of an action potential. This lengthens the QT interval of the heartbeat as well as prolonging the repolarization phase of action potentials. This regulates the heart rate and slows down any rapid heartrates.

Metabolites of Sotalol are predicted with biotransformer.