Pathways

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.

glucose is metabolized in the cell via two main pathways- Glycolysis and TCA cycle.

Trichlormethiazide is a pharmacologically-active small molecule that belongs to a class of drugs called thiazides. Thiazides and thiazide-like drugs are diuretics commonly employed to control hypertension. Trichloromethiazide acts by inhibiting chloride and potentially sodium reabsorption in the ascending loop of Henle, specifically at solute carrier family 12 member 3. This action results in increased fluid loss which ultimately reduces blood volume and pressure. Trichlormethiazide also acts to inhibit sodium uptake and increase potassium excretion which also serves to increase fluid loss. The long-term antihypertensive effects of thiazides and thiazide-like drugs such as trichlormethiazide are not well-characterized but may involve its action on carbonic anhydrases.

Trichloromethiazide is an oral diuretic drug that acts in the kidney, specifically in the distal convoluted tubule of the nephron. It is used in the treatment of edema (including that associated with heart failure) and hypertension. In the distal convoluted tubule (DCT), the regulation of ions such as sodium, potassium, calcium, chloride, and magnesium occurs. In epithelial cells of the DCT, the basolateral membrane consists of the Na+/K+ ATPase, which pumps Na+ into the interstitium-blood area and K+ into the epithelial cell; the Na+/Ca2+ exchanger, which pumps Na+ into the cell and Ca2+ into the interstitium-blood; and the chloride transporter which transports chloride into the interstitium-blood. The apical membrane contains a calcium channel that transports calcium from the lumen into the epithelial cell, a potassium channel that transports K+ out of the epithelial cell, and a Na+/Cl- cotransporter which transports Na+ and Cl- into the epithelial cell. Trichloromethiazide targets this Na+/Cl- cotransporter. Trichloromethiazide is transported from the blood into the epithelial cells, then is transported into the urine through the multidrug-resistant associated protein-4. In the lumen, it has access to the Na+/Cl- transporter and inhibits it preventing Na+ reabsorption. The inhibition of Na+ reabsorption results in a low cytosolic concentration of Na+ and increases the solute concentration of the lumen. This decreases the lumen-epithelial cell concentration gradient and as a result, less water would be reabsorbed from the urine. This effect is valued in conditions such as hypertension because it allows more water to be excreted in the urine rather than be absorbed in the blood which increases blood volume. Side effects such as nausea, vomiting, diarrhea, headache, dizziness, flushing, loss of appetite, weakness, and abdominal pain can occur from taking trichloromethiazide. This drug is administered as an oral tablet.