Angiotensin II-Receptor Antagonists

PHRM 306: Drugs affecting CVS

ARBs
Angiotensin-receptor blockers (ARBs) are nonpeptide, extremely potent competitive antagonists of the angiotensin type 1 receptor. ARBs have the advantage of more complete blockade of angiotensin action, because ACE inhibitors inhibit only one enzyme responsible for the production of angiotensin II.

ARBs
The angiotensin II-receptor blockers (ARBs) are alternatives to the ACE inhibitors. These drugs block the AT1 receptors. Losartan, is the prototypic ARB; currently, there are six additional ARBs. Valsartan, Irbesartan, Candesartan, Telmesatran, Eprosartan

ARBs: CVS
Their pharmacologic effects are similar to those of ACE inhibitors in that they produce arteriolar and venous dilation and block aldosterone secretion, thus lowering blood pressure and decreasing salt and water retention.

ARBs: CVS
The drugs are used in heart failure as a substitute for ACE inhibitors in those patients with severe cough or angioedema.

Pharmacokinetics
All the drugs are orally active and require only once-a-day dosing. Losartan, the first approved member of the class, differs from the others in that it undergoes extensive first-pass hepatic metabolism, including conversion to its active metabolite. The other drugs have inactive metabolites.

Pharmacokinetics
Elimination of metabolites and parent compounds occurs in the urine and feces; the proportion is dependent on the individual drug. All are highly plasma protein-bound (greater than 90 percent) and, except for candesartan, have large volumes of distribution.

ARBs: Adverse effects

ARBs do not increase bradykinin levels. Thus the risks of cough and angioedema are significantly decreased. ARBs decrease the nephrotoxicity of diabetes, making them an attractive therapy in hypertensive diabetics. Their other adverse effects are similar to those of ACE inhibitors.

ARBs: Adverse effects

ARBs are also fetotoxic.

PHRM 306: Drugs affecting CVS

RENIN INHIBITORS

Renin inhibitors
A selective renin inhibitor, aliskiren has been used for the treatment of hypertension. Aliskiren directly inhibits renin and, thus, acts earlier in the renin-angiotensin-aldosterone system than ACE inhibitors or ARBs.

Renin inhibitors
It lowers blood pressure about as effectively as ARBs, ACE inhibitors, and thiazides. It can also be combined other antihypertensives, such diuretics, ACE inhibitors, ARBs, or calcium-channel blockers.

Renin inhibitors
Aliskiren can cause diarrhea, especially at the higher doses. Aliskiren can also cause cough and angioedema but probably less often than ACE inhibitors. The drug is contraindicated during pregnancy.

Renin inhibitor
The combination of maximum doses of aliskiren and valsartan decreased blood pressure more than maximum doses of either agent alone but not more than would be expected with dual therapy consisting of agents of different classes. Hyperkalemia was significantly more common in patients who received both valsartan and aliskiren.