AT1 Blockers

Question 1

Example of an ATI blocker (Angiotensin receptor blockers ARBs)

Answer 1

Losartan

Question 2

How do ARBs blockers work?

Answer 2

ARBs have similar effects to ACE inhibitors, but instead of inhibiting the conversion of angiotensin I to angiotensin II, ARBs block the action of angiotensin II on the AT1 receptor. Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion. Blocking its action reduces peripheral vascular resistance (afterload), which lowers blood pressure. It particularly dilates the efferent glomerular arteriole, which reduces intraglomerular pressure and slows the progression of CKD. Reducing the aldosterone level promotes sodium and water excretion. This can help to reduce venous return (preload), which has a beneficial effect in heart failure.

Question 3

Indications of ARBs blockers

Answer 3

Hypertension: for the first- or second-line treatment of hypertension, to reduce the risk of stroke, myocardial infarction and death from cardiovascular disease.

Chronic heart failure: for the first-line treatment of all grades of heart failure, to improve symptoms and prognosis.

Ischaemic heart disease: to reduce the risk of subsequent cardiovascular events such as myocardial infarction and stroke.

Diabetic nephropathy and chronic kidney disease (CKD) with proteinuria: to reduce proteinuria and progression of nephropathy

Question 4

Contra-indications of ARBs blockers

Answer 4

ARBs should be avoided in patients with renal artery stenosis or acute kidney injury; in women who are, or could become, pregnant; and those who are breastfeeding. Although ARB therapy is potentially valuable in some forms of chronic kidney disease, lower doses should be used and the effect on renal function monitored closely.

Question 5

Side effects of ARBs blockers

Answer 5

ARBs can cause hypotension (particularly after the first dose), hyperkalaemia and renal failure. The mechanism is the same as for ACE inhibitors. Patients most at risk of renal failure are those with renal artery stenosis, who rely on constriction of the efferent glomerular arteriole to maintain glomerular filtration.

Unlike ACE inhibitors, ARBs are less likely to cause a dry cough, as they do not inhibit ACE, and therefore do not affect bradykinin metabolism. For the same reason, they are less likely to cause angioedema.

Question 6

Interactions of ARBs blockers

Answer 6

Due to the risk of hyperkalaemia, avoid prescribing ARBs with other potassium-elevating drugs, including potassium supplements (oral or IV) and potassium-sparing diuretics except under specialist advice for advanced heart failure.

In combination with other diuretics they may be associated with profound first-dose hypotension.

The combination of NSAIDs with ARBs increases the risk of renal failure.

Question 7

Elimination of ARBs blockers

Answer 7

Renal

Question 8

Patient information of ARBs blockers

Answer 8

ARBs are taken orally. They can be taken with or without food. It is best to take the first dose before bed to reduce symptomatic hypotension.

Explain that you are offering treatment with a medicine to improve their blood pressure and reduce strain on their heart. If the patient has previously been unable to tolerate an ACE inhibitor due to cough, explain that the new treatment does not cause this side effect.

Advise patients about the possibility of dizziness due to low blood pressure, particularly after the first dose. Make sure they understand the need for blood test monitoring, explaining that ARBs can interfere with their kidney function and upset potassium balance.

Advise them to avoid taking over-the-counter anti-inflammatories (e.g. ibuprofen) due to the risk of kidney damage.