(Losartan) Overview on the first approved Angiotensin-receptor blocker

 

Losartan

Overview on the first approved

Angiotensin-receptor blocker

 

Content

 ·    Drug Class &Brand Name

 ·    Clinical Uses

 ·    Mechanism of action

 ·    Dosage & Administration

 ·    Key side effects

 ·    Pregnancy

 ·    Pharmacokinetics

 ·    Drug interactions

 ·    Summary

 

Drug Class

·    Angiotensin II Receptor Blocker

·    Antihypertensive

Brand Name

·    Cozaar

Clinical Uses

·    Hypertension

·    Initial: 25 to 50 mg once daily.

·    Max: 100 mg per day.

·    Acute coronary syndromes

·    Alternative in patients who cannot

tolerate ACE inhibitor.

·    Heart failure (HFrEF)

·    Posttransplant erythrocytosis

·    Proteinuric chronic kidney disease

Mechanism of action

1.                Block the AT1 receptors

2.                Inhibit angiotensin II effect -> block the vasoconstriction effect

3.                Block release of aldosterone -> less sodium retention In the body

4.                Lower blood pressure -> antihypertensive effect

5.                Also increase urinary flow rate and increases excretion of calcium, chloride, magnesium and uric acid.

Dosage & Administration

·    In Hypertension;

Usual adult dose: 50mg once daily

Usual pediatric starting dose: 0.7 mg per kg once daily (up to 50 mg)

·    In Hypertensive Patients with Left tr lar Hypertrophy;

Usual starting dose: 50mg once daily Add hydrochlorothiazide 12.5mg

 to 100 mg losartan

followed by an increase to hydrochlorothiazide 25mg

if further blood pressure response is needed.

Key side effects

·    Acute kidney injury

·    Inhibit efferent kidney arteriolar vasoconstriction-> Lower glomerular filtration pressure and lead to a reduction in GFR.

·    Hyperkalaemia

·    Decrease aldosterone release -> Impair kidney potassium excretion.

·    Usually occurs within 1 week of Treatment initiation.

Pregnancy

·    NOT recommended

·    Drugs that act on the RAAS can lead to fetal injury, such as decreased renal function, lung hypoplasia and skeletal malformations.

·    In serious case, it will cause death to the developing fetus.

·    When pregnancy is detected, discontinue as soon as possible.

Pharmacokinetics

·    Absorption:

Following oral administration, Losartan is well absorbed and undergoes substantial first-pass metabolism; the systemic bioavailability of Losartan is approximately 33%.

·    Distribution:

The volume of distribution of Losartan and the active metabolite is about 34 liters and 12 liters, respectively.

·    Biotransformation:

About 14% of an orally administered dose of Losartan is converted to the active metabolite. 

·    Metabolism:

Losartan Potassium undergoes substantial first-pass metabolism by cytochrome P450 enzymes. In vitro studies indicate that cytochrome P450 2C9 and 3A4 are involved in the biotransformation of Losartan to its metabolites.

·    Excretion:

When Losartan is administered orally, about 4% of the dose is excreted unchanged in the urine and about 6% is excreted in urine as active metabolite.

Drug interactions

1. Lithium: Risk of lithium toxicity.

2. NSAIDs: Increased risk of renal impairment and reduced diuretic, natriuretic, and antihypertensive effects.

3. Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, syncope, and hyperkalaemia.

Summary

·    Losartan is Angiotensin II Receptor Blocker( 

( ARB) that is used for hypertension and acute coronary syndromes.

·    It works by blocking the AT1 receptors, and cause downstream action in reducing the blood pressure.

·    Acute kidney injury and hyperkalaemia are two key side effects to take note.

·    Do NOT use ARB in pregnant patients.