A2A Tab 25 mg (Losartan Potassium)

Here’s the detailed information you’ve requested for Losartan Potassium, which is the active ingredient in A2A Tab 25 mg.

Chemical Name and Formula:

• Chemical Name:
  **(S)-2-Butyl-4-chloro-1-[p-(2′-tetrazol-5-ylbiphenyl-4-yl)phenyl]methylthio]-1H-imidazole-5-methanol potassium salt.
• Molecular Formula:
  C22H23ClN6O | K
  • Losartan itself: C22H23ClN6O
  • Potassium salt form: C22H23ClN6OK (this represents the potassium component, which is part of the salt form in the tablet).

Pharmacodynamics:

Pharmacodynamics refers to how a drug affects the body, particularly its mechanism of action:

1. Mechanism of Action:
   • Losartan is an angiotensin II receptor antagonist (ARB), specifically a type 1 (AT1) receptor blocker. Angiotensin II is a potent vasoconstrictor that narrows blood vessels, leading to higher blood pressure. By blocking the AT1 receptor, Losartan prevents the binding of angiotensin II, which in turn helps relax blood vessels and lowers blood pressure.
   • This action also reduces the secretion of aldosterone and vasopressin, both of which contribute to blood pressure regulation and fluid retention.
2. Effects on the Cardiovascular System:
   • Losartan reduces vascular resistance, thus lowering systemic blood pressure.
   • It has also been shown to reduce the workload on the heart, which is beneficial in heart failure management.
3. Other Effects:
   • By inhibiting the angiotensin II effects, Losartan can help prevent kidney damage, especially in diabetic patients, and protect against stroke in individuals with hypertension.

Pharmacokinetics:

Pharmacokinetics refers to how the drug is absorbed, distributed, metabolized, and excreted by the body.

1. Absorption:
   • Losartan is well absorbed from the gastrointestinal tract after oral administration. However, it has a low bioavailability (approximately 33%) due to first-pass metabolism in the liver.
   • The onset of action typically occurs within 6 hours, with peak effects seen at 6–8 hours post-dose.
2. Distribution:
   • Losartan is highly protein-bound (about 99%), which means it mainly circulates bound to plasma proteins in the bloodstream.
   • Volume of distribution (Vd): Approximately 34 L (suggesting it is widely distributed in the body).
3. Metabolism:
   • Losartan is extensively metabolized in the liver, primarily by the enzyme cytochrome P450 2C9 (CYP2C9). The primary active metabolite, E3174, is approximately 10–40 times more potent than Losartan itself in blocking the AT1 receptor.
   • Losartan’s metabolism also involves CYP3A4, although CYP2C9 plays the more dominant role.
4. Excretion:
   • Losartan and its metabolites are primarily excreted in the urine (approximately 35% of the dose) and feces (about 60%).
   • The half-life of Losartan is about 2 hours; however, the half-life of its active metabolite (E3174) is significantly longer at about 6–9 hours. This gives Losartan a prolonged duration of action.

Half-Life:

• Losartan: 2 hours
• Active Metabolite (E3174): 6–9 hours

The long half-life of the active metabolite contributes to its sustained effect, allowing Losartan to be effective with once-daily dosing.

Drug Interactions:

Drug Interactions:

Losartan can interact with several classes of drugs, which may enhance or reduce its effects. Some important interactions include:

1. Antihypertensive Agents:
   • Other antihypertensive drugs (e.g., ACE inhibitors, diuretics, calcium channel blockers) can enhance the blood pressure-lowering effect of Losartan, potentially leading to hypotension (low blood pressure).
   • Diuretics (especially potassium-sparing diuretics) can increase the risk of hyperkalemia (high potassium levels) when combined with Losartan.
2. Potassium Supplements:
   • Potassium supplements or potassium-sparing diuretics (e.g., spironolactone) can lead to dangerous hyperkalemia (elevated potassium levels). Monitoring of potassium levels is recommended.
3. NSAIDs (Nonsteroidal Anti-Inflammatory Drugs):
   • NSAIDs (e.g., ibuprofen, naproxen) can reduce the effectiveness of Losartan and may increase the risk of kidney damage, especially when used long-term. Concomitant use may require monitoring of kidney function.
4. Lithium:
   • Losartan can increase the plasma concentration of lithium, which may enhance its toxic effects. Regular monitoring of lithium levels is necessary if both drugs are used together.
5. Angiotensin-converting enzyme inhibitors (ACE inhibitors):
   • ACE inhibitors (e.g., enalapril, lisinopril) and Losartan, both being part of the renin-angiotensin system (RAS) blockade, may cause excessive lowering of blood pressure or renal dysfunction when used together.
6. Rifampicin:
   • Rifampicin (an antibiotic) may increase the metabolism of Losartan, reducing its effectiveness.

Food and Drug Interactions:

• Food Interactions:
  • Losartan can be taken with or without food, as food does not significantly affect the absorption or effectiveness of the drug.
  • However, it is best to avoid high-salt or high-potassium foods while taking Losartan, as these can alter potassium balance and contribute to complications like hyperkalemia.
• Alcohol:
  • Alcohol can exacerbate the blood pressure-lowering effects of Losartan, leading to an increased risk of dizziness or fainting. It is advisable to limit alcohol consumption while on Losartan.