Azilsartan

MECHANISM OF ACTION

Azilsartan works as an angiotensin II receptor blocker (ARB) by specifically targeting the angiotensin II type 1 receptor (AT1), which plays a key role in the harmful effects of angiotensin II.

Angiotensin II Binding: Under normal circumstances, angiotensin II binds to the AT1 receptors in blood vessels, the heart, kidneys, and other tissues. This causes blood vessels to narrow (vasoconstriction), leading to an increase in blood pressure. It also stimulates the release of aldosterone, a hormone that causes the kidneys to hold onto sodium and water, raising blood pressure further.

Azilsartan's Action: Azilsartan blocks the AT1 receptor, preventing angiotensin II from binding. This blocks the vasoconstrictions effects and reduces the release of aldosterone, which results in vasodilation, or relaxation of blood vessels, which helps to lower blood pressure. Decreased aldosterone secretion, which helps reduce sodium and water retention, further aiding in blood pressure reduction. By blocking the effects of angiotensin II, azilsartan helps relax blood vessels, reduce the strain on the heart, and lower blood pressure.

PHARMACOKINETICS

Absorption:

Azilsartan is easily absorbed after oral intake. It reaches its peak concentration in the blood around 2 to 3 hours after consumption. The drug has a bioavailability of about 60-70% when taken on an empty stomach, with food slightly increasing absorption but not affecting its effectiveness significantly.

Distribution:

Azilsartan is widely distributed throughout the body. It has a high volume of distribution, meaning it spreads extensively in tissues. The drug is highly bound to plasma proteins (around 99%), mainly albumin.

Metabolism:

Azilsartan is minimally metabolized in the liver. It is not significantly affected by cytochrome P450 enzymes, reducing the chance of drug interactions with substances that impact these enzymes. Most of the drug remains in its active form in the body, with only a small portion metabolized.

Elimination:

Azilsartan has a half-life of about 11 hours, allowing for once-daily use. It is mostly eliminated through feces, with less than 1% of the dose excreted in urine. Renal clearance is minimal, as the drug isn’t significantly excreted through the kidneys.

DOSAGE AND ADMINISTRATION

• Initial dose: 40 mg once daily.
• Maintenance dose: 40 mg to 80 mg once daily.
• Max dose: 80 mg daily.

Special Cases:

• Hepatic impairment: Use with caution; avoid in moderate to severe impairment.
• Renal impairment: Safe for moderate impairment; avoid in severe impairment.

Take once daily with or without food

DRUG INTERACTIONS

• Other antihypertensives: Additive BP-lowering effect.
• Potassium-sparing diuretics/potassium supplements: Increased risk of hyperkalemia.
• NSAIDs: Reduced antihypertensive effect; may cause renal issues.
• Lithium: Increases lithium levels, risk of toxicity.
• ACE inhibitors/ARBs: Increased risk of hypotension, hyperkalemia, and renal dysfunction.
• Diuretics: Increased risk of dehydration and renal issues.

CONTRAINDICATIONS

Hypersensitivity to azilsartan

Pregnancy (especially in the second and third trimesters)

Severe renal impairment (creatinine clearance <30 mL/min)

Bilateral renal artery stenosis

SIDE EFFECTS

Common side effects

• Dizziness or feeling lightheaded, particularly when standing.
• Tiredness or fatigue.
• Increased potassium levels (hyperkalemia).
• Low blood pressure (hypotension).
• Headache.
• Diarrhea.

Serious side effects may include:

• Severe low blood pressure (hypotension).
• Kidney issues, such as changes in kidney function or kidney failure.
• Angioedema (swelling, especially in the face, lips, tongue, or throat).

TOXICITY

Toxicity from azilsartan is uncommon but possible, especially in cases of overdose. Symptoms may include:

• Severe low blood pressure (hypotension), which can lead to dizziness, fainting, or shock
• High potassium levels (hyperkalemia), causing irregular heartbeats, muscle weakness, or paralysis
• Kidney problems, including acute kidney failure
• Slow heart rate (bradycardia)