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Trichlormethiazide | CAS No: 133-67-5 | GMP-certified suppliers
A medication that treats edema linked to heart failure and various renal conditions, and manages hypertension by promoting diuresis and reducing blood pressure.
Therapeutic categories
Primary indications
- Used in the treatment of oedema (including that associated with heart failure) and hypertension
Product Snapshot
- Trichlormethiazide is an oral small molecule available in pill and tablet formulations
- It is primarily indicated for the management of oedema and hypertension
- The product holds approved status for human use and veterinary applications
Clinical Overview
Clinically, Trichlormethiazide is indicated for edema associated with congestive heart failure, hepatic cirrhosis, corticosteroid or estrogen therapy, and various renal dysfunctions including nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. It is also employed in hypertension management either as monotherapy or in combination with other antihypertensive agents, particularly in severe cases.
The pharmacological action of Trichlormethiazide involves inhibition of sodium and chloride reabsorption primarily in the distal convoluted tubule through blockade of the thiazide-sensitive sodium-chloride symporter. This inhibition decreases electrolyte reabsorption, leading to increased urinary excretion of sodium, chloride, and water, which contributes to its diuretic effect. Additionally, Trichlormethiazide promotes potassium loss via enhanced sodium-potassium exchange in renal tubules. While the precise mechanism underlying its antihypertensive effect remains unclear, evidence indicates it may involve vasodilation mediated by activation of large-conductance calcium-activated potassium channels in vascular smooth muscle and inhibition of vascular carbonic anhydrase enzymes.
Key ADME characteristics include renal excretion of unchanged drug and diuretic-induced changes in electrolyte balance that require monitoring. Safety considerations involve potential risks of hypokalemia, hyperuricemia, and electrolyte disturbances. Careful patient assessment is advised, especially in those with renal impairment or histories of gout. Trichlormethiazide is approved for human use and veterinary applications.
Notable pharmaceutical formulations often combine Trichlormethiazide with antihypertensive agents to optimize therapeutic effects.
From an API sourcing and quality perspective, compliance with pharmacopeial standards for identity, purity, and assay is essential. Sourcing should ensure absence of contaminants and consistent batch-to-batch quality, given the compound’s sulfonamide structure and potential for hypersensitivity reactions. Robust analytical characterization including chromatographic and spectroscopic methods supports regulatory compliance and safe formulation development.
Identification & chemistry
| Generic name | Trichlormethiazide |
|---|---|
| Molecule type | Small molecule |
| CAS | 133-67-5 |
| UNII | Q58C92TUN0 |
| DrugBank ID | DB01021 |
Pharmacology
| Summary | Trichlormethiazide is a thiazide diuretic that inhibits the Na⁺/Cl⁻ symporter in the distal convoluted tubule, reducing sodium and chloride reabsorption and promoting diuresis. Its pharmacodynamic effects include increased excretion of sodium, chloride, potassium, and water, contributing to its utility in edema and hypertension management. Additional mechanisms may involve modulation of vascular smooth muscle via carbonic anhydrase inhibition and activation of large-conductance calcium-activated potassium channels. |
|---|---|
| Mechanism of action | Trichlormethiazide seemingly appears to inhibit the active reabsorption of chloride in the ascending loop of Henle. Additionally, it may also do the same for sodium. These actions subsequently alter electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, Trichloromethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like Trichloromethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of Trichloromethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. |
| Pharmacodynamics | Trichloromethiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Trichloromethiazide has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomer-ulonephritis, and chronic renal failure. Trichloromethiazide is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. Like other thiazides, Trichloromethiazide promotes water loss from the body (diuretics). They inhibit Na<sup>+</sup>/Cl<sup>-</sup> reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Solute carrier family 12 member 3 | Humans | inhibitor |
| Sodium/potassium-transporting ATPase subunit alpha-1 | Humans | inhibitor |
| Carbonic anhydrase 1 | Humans | inhibitor |
Formulation & handling
- Trichlormethiazide is a small molecule drug formulated primarily for oral administration as tablets or pills.
- Due to its moderate water solubility and low LogP, formulation strategies should consider enhancing bioavailability.
- Stable under standard storage conditions, no special handling precautions related to peptide or biologic properties are required.
Regulatory status
Supply Chain
| Supply chain summary | Trichlormethiazide is supplied by multiple manufacturers, including several that originated as branded product developers, reflecting a diversified production base. Branded products have a global presence, particularly in the US and EU markets. The presence of numerous manufacturers and packagers, along with patent expiry, indicates established generic competition in this API segment. |
|---|
Safety
| Toxicity | Oral Rat LD<sub>50</sub> = 5600 mg/kg, oral Mouse LD<sub>50</sub> = 2600 mg/kg |
|---|
- Handle with appropriate personal protective equipment to prevent ingestion and minimize exposure
- Toxicity data indicate moderate acute oral toxicity
- Avoid release to environment
Trichlormethiazide is a type of Diuretics
Diuretics, a subcategory of pharmaceutical active pharmaceutical ingredients (APIs), are compounds commonly used in the treatment of conditions such as hypertension, congestive heart failure, and edema. Diuretics, also known as water pills, function by increasing the production of urine, thereby promoting the excretion of excess water and electrolytes from the body.
There are several types of diuretics, including thiazide diuretics, loop diuretics, and potassium-sparing diuretics. Thiazide diuretics, such as hydrochlorothiazide, work by inhibiting the reabsorption of sodium and chloride in the kidneys, leading to increased urine production. Loop diuretics, such as furosemide, act on the loop of Henle in the kidneys to block the reabsorption of sodium and chloride, resulting in a more potent diuretic effect. Potassium-sparing diuretics, like spironolactone, help retain potassium in the body while still promoting diuresis.
These diuretic APIs are widely used in the pharmaceutical industry to formulate medications that effectively manage fluid retention and related conditions. They are available in various forms, including tablets, capsules, and intravenous formulations. Diuretics are often prescribed as part of combination therapies to enhance their effectiveness and minimize adverse effects.
It is important to note that the use of diuretics should be closely monitored by healthcare professionals due to potential side effects such as electrolyte imbalances, dehydration, and hypotension. Proper dosage and patient-specific considerations are crucial to ensure optimal therapeutic outcomes.
In conclusion, diuretics are a vital subcategory of pharmaceutical APIs used to treat conditions characterized by fluid retention. Their mechanisms of action vary, but they all facilitate increased urine production, assisting the body in eliminating excess fluids. The proper use of diuretics, in combination with medical supervision, can effectively manage various cardiovascular and renal conditions.
Trichlormethiazide (Diuretics), classified under Antihypertensive agents
Antihypertensive agents are a crucial category of pharmaceutical active pharmaceutical ingredients (APIs) used to treat high blood pressure, also known as hypertension. These medications are designed to lower blood pressure and reduce the risk of associated cardiovascular complications.
Antihypertensive agents function by targeting various mechanisms involved in blood pressure regulation. Some common classes of antihypertensive agents include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs), and diuretics.
ACE inhibitors work by inhibiting the enzyme responsible for converting angiotensin I to angiotensin II, a hormone that constricts blood vessels. ARBs, on the other hand, block the receptors to which angiotensin II binds, thereby preventing its vasoconstrictive effects.
Beta-blockers reduce blood pressure by blocking the effects of adrenaline and noradrenaline, which are responsible for increasing heart rate and constricting blood vessels. CCBs inhibit calcium from entering the smooth muscles of blood vessels, resulting in relaxation and vasodilation. Diuretics promote the elimination of excess fluid and sodium from the body, reducing blood volume and thereby lowering blood pressure.
Antihypertensive agents are typically prescribed based on the individual patient's condition and specific needs. They can be used alone or in combination to achieve optimal blood pressure control. It is important to note that antihypertensive agents should be taken regularly as prescribed by a healthcare professional and may require periodic monitoring to ensure their effectiveness and manage any potential side effects.
In summary, antihypertensive agents play a vital role in the management of hypertension by targeting various mechanisms involved in blood pressure regulation. These medications offer significant benefits in reducing the risk of cardiovascular complications associated with high blood pressure.
Trichlormethiazide API manufacturers & distributors
Compare qualified Trichlormethiazide API suppliers worldwide. We currently have 2 companies offering Trichlormethiazide API, with manufacturing taking place in 2 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Derivados Quimicos | Producer | Spain | Spain | CoA, GMP | 18 products |
| Iwaki Seiyaku | Producer | Japan | Japan | CoA, JDMF | 21 products |
When sending a request, specify which Trichlormethiazide API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
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