ARBs: prototype drugvalsartan

a. Mechanism. Valsartan is an imidazole derivative with high affinity for AT1 receptors
(about 20,000-fold higher than for AT2 receptors).
(1) Oral doses are absorbed rapidly. Peak levels of the drug are obtained in about
3 hours, and it has a half-life of about 6 hours.
(2) Valsartan is excreted in the feces, probably via biliary excretion.
b. Therapeutic uses. In clinical trials, valsartan was about as effective as captopril in
patients with LV dysfunction following an MI. Valsartan is as effective as ACE inhibitors
in reducing blood pressure and is available in combination with hydrochlorothiazide
for patients refractory to monotherapy.
c. Adverse effects and contraindications. Dizziness and hyperkalemia can
occur with valsartan.
Since ARBs do not lead to accumulation of kinins, the incidence of both the
nonproductive cough and angioedema associated with ACE inhibitors is reduced.
d. All other ARBs (see Table 4.1) have the same mechanism of action and adverse effect
profile but have subtle pharmacokinetic differences. They vary markedly in their
relative
affinity for AT1 and AT2 receptors.