Pathways

A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. The biosynthesis of triacylglycerol is localized to the endoplasmic reticulum membrane and starts with glycerol 3-phosphate reacting with acyl-CoA through a glycerol-3-phosphate O-acyltransferase resulting in the release of lysophosphatidic acid (LPA). This, in turn, reacts with an acyl-CoA through a lipase complex resulting in the release of CoA and phosphatidic acid. Phosphatidic acid reacts with water through a phosphatidic acid phosphohydrolase 1 resulting in the release of a phosphate and a diacylglycerol. This reaction can be reversed through a CTP-dependent diacylglycerol kinase. The diacylglycerol reacts in the endoplasmic reticulum with an acyl-CoA through a diacylglycerol O-acyltransferase resulting in the release of coenzyme A and a triacylglycerol. Triacylglycerol metabolism begins with a reaction with water through lipase resulting in the release of a fatty acid, hydrogen ion, and a diacylglycerol. Diacylglycerol then reacts with a lipase 3 resulting in the release of a fatty acid and a monoacylglycerol. Monoacylglycerol reacts with monoglyceride lipase resulting in the release of a fatty acid in glycerol.

Triamcinolone is a glucocorticoid used to treat a wide variety of inflammatory conditions. As this drug is a glucocorticoid, its mechanism of action is that of the glucocorticoid response element (GRE) influencing COX-2/prostaglandin G/H synthase 2 suppression and lipocortin/annexin induction. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence the effects of inflammation through vasoconstriction/dilation, pain sensitivity, and platelet aggregation. Triamcinolone also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases the concentrations of prostanoids mentioned calming inflammation. This drug is available as tablets, eye drops, creams, intramuscular and intravenous injections, and as a nasal spray.

Metabolites of Triamcinolone are predicted with biotransformer.

Triamterene is a diuretic that belongs to the potassium-sparing class of drugs which are commonly used to manage hypertension and edema. It acts by blocking epithelial sodium channels in the late distal convoluted tubule of the nephron. Specifically, triamterene inhibits amiloride-sensitive sodium channels which are responsible for the reabsorption of sodium in the late distal convoluted tubule in the nephron. This primarily contributes to an increase in sodium excretion and consequentially, fluid excretion which decreases blood volume and blood pressure. Potassium secretion is indirectly affected by the inhibition of sodium reabsorption due to the elimination of the electrochemical gradient that drives potassium loss. This leads to an increase in serum potassium concentration -- a common action for potassium-sparing drugs -- and has the potential to induce hyperkalemia which can potentially lead to severe heart arrhythmias.

Triamterene is a potassium-sparing diuretic used in the treatment of edema and in the management of hypertension. It can be found under the brand names Dyrenium and Maxzide. Triamterene (2,4,7-triamino-6-phenylpteridine) is a potassium-sparing diuretic that is used in the management of hypertension. It works by promoting the excretion of sodium ions and water while decreasing the potassium excretion in the distal part of the nephron in the kidneys by working on the lumenal side. Since it acts on the distal nephron where only a small fraction of sodium ion reabsorption occurs, triamterene is reported to have limited diuretic efficacy. Due to its effects on increased serum potassium levels, triamterene is associated with a risk of producing hyperkalemia. Triamterene inhibits the epithelial sodium channels (ENaC) located on the lumenal side in the late distal convoluted tubule and collecting tubule, which are transmembrane channels that normally promote sodium uptake and potassium secretion. In the late distal tubule to the collecting duct, sodium ions are actively reabsorbed via ENaC on the luminal membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase, with water following passively. Triamterene exerts a diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium ions in exchange for potassium and hydrogen ions and its natriuretic activity is limited by the amount of sodium reaching its site of action. Its action is antagonistic to that of adrenal mineralocorticoids, such as aldosterone, but it is not an inhibitor or antagonist of aldosterone. Triamterene maintains or increases sodium excretion, thereby increasing the excretion of water, and reducing the excess loss of potassium, hydrogen, and chloride ions by inhibiting the distal tubular exchange mechanism. Due to its diuretic effect, triamterene rapidly and reversibly reduces the lumen-negative transepithelial potential difference by almost completely abolishing Na+ conductance without altering K+ conductance. This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion. Triamterene is similar in action to amiloride but, unlike amiloride, increases the urinary excretion of magnesium. Some side effects of using triamterene may include stomach pain, agitation, and cloudy urine.

Triazolam is a short-acting benzodiazepine used for the short-term treatment of insomnia (hypnotic agent). This drug binds to various regions of the brain and spinal cord where GABA A receptors are. It binds to an allosteric site between the alpha and gamma subunits of the receptor increasing the inhibitory effects of GABA. Benzodiazepines bind nonspecifically to BNZ1, which acts on sleep, and BNZ2, which acts on muscle relaxation, anticonvulsant activity, motor coordination, and memory. These receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. In consequence, when GABA binds the site, it opens the chloride channel, resulting in a hyperpolarized cell membrane. Since the neuron cell is hyperpolarized, it prevents further excitation of the cell. Triazolam is administered orally as a tablet. Overdosing of triazolam usually has the symptoms of more intense therapeutic effects with extreme overdosage leading to coma, cardio-respiratory depression, and apnoea. Due to its high affinity for plasma proteins, diazepam also has a high volume of distribution and can cross the blood-brain barrier. This drug has been withdrawn in the United Kingdom due to the risk of psychiatric adverse drug reactions. This drug continues to be available in the U.S..

Metabolites of Triazolam are predicted with biotransformer.