Core pharmacology

Class Group

Angiotensin Receptor Blocker

Legacy Cicm Level

Level 3

Introduction

substituted imidazole compound which selectively blocks AT2
receptors throughout the body.

Indications Uses

1. essential and renovascular hypertension
2. diabetic nephropathy
3. congestive cardiac failure, and
4. in patients intolerant of angiotensin-converting enzyme inhibitors (ACEIs).

Presentation

presented in 50mg tablets.
Combo not available
(available overseas with thiazide)

Mechanism of action

Eff¬ects are broadly similar to ACE inhibitors. The blocking of AT2 receptors reduces the action of angiotensin II.

Onset Peak Duration

on/dur 6 hours, prolonged action due to metabolite

Physiological effects

Notably as ACE is not inhibited, there is not increased levels of bradykinin, hence there is less cough associated with ARBs and possibly
less vasodilation and peripheral oedema attributed to bradykinin levels

Adverse Effects Toxicity

Contraindicated like ACE inhibitors in bilateral renal artery stenosis, and
pregnancy. Caution in sodium depleted patients similar to ACE inhibitors

Absorption

PO. Well absorbed from the gut but extensive first pass metabolism leads to BA of 25% to 33%,

Protein binding

98%

Volume of distribution

0.48 L/kg

Metabolism

Hepatic (14%) via CYP2C9 and 3A4 to active metabolite, E-3174 (40 times more potent than losartan)

Excretion

Urine (4% as unchanged drug, 6% as active

Half-life

1.5-2 hours
E-3174 6-9 hours

Route And Dose

PO: doses 50-100mg daily