These substances are AT1-receptor antagonists; that is, they block the activation of<unk> <unk>  AT1 receptors. AT1 receptors are found in smooth muscle cells of vessels, cortical cells of the adrenal gland, and adrenergic nerve synapses. Blockage of AT1 receptors directly causes vasodilation, reduces secretion of vasopressin, and reduces production and secretion of aldosterone, among other actions. The combined effect reduces blood pressure. The specific efficacy of each<unk>  within this class depends upon a combination of three pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Efficacy requires three key PD/PK areas at an effective level; the parameters of the three characteristics will need to be compiled into a table similar to one below, eliminating duplications and arriving at consensus values; the latter are at variance now. Pressor inhibition Pressor inhibition at trough level - this relates to the degree of blockade or inhibition of the blood pressure-raising ("pressor") effect of<unk> <unk> . However, pressor inhibition is not a measure of blood pressure-lowering (BP) efficacy per se. The rates as listed in the U.S. Food and Drug Administration (FDA) Package Inserts (PIs) for inhibition of this effect at the 24th hour for the<unk> s are as follows: (all doses listed in PI are included) *Valsartan 80 mg 30% *Telmisartan 80 mg 40% *Losartan 100 mg 25–40% *Irbesartan 150 mg 40% *Irbesartan 300 mg 60% *Azilsartan 32 mg 60% *Olmesartan 20 mg 61% *Olmesartan 40 mg 74% AT1 affinity vs AT2 The ratios of AT1 to AT2 in binding affinities of the specific<unk> s are shown as follows. However, AT1 affinity vs AT2 is not a meaningful indicator of blood pressure response. *Losartan – 1000-fold *Telmisartan – 3000-fold *Irbesartan – 8500-fold *Candesartan – greater than 10000-fold *Olmesartan – 12500-fold *Valsartan – 30000-fold higher than AT2 (the ratio of binding affinities of valsartan to AT1 and AT2 is 30000:1) *Saprisartan – ??? Binding affinities Ki Component Nearly all<unk> s contain biphenyltetrazole moiety except telmisartan and eprosartan. Active agent Losartan carries a heterocycle imidazole while valsartan carries a nonplanar acylated amino acid. Biological half-life The third area needed to complete the overall efficacy picture of an<unk>  is its biological half-life. The half-lives from the U.S. Food and Drug Administration (FDA) package inserts (PIs) are as follows: *Valsartan 6 hours *Losartan 6–9 hours *Azilsartan 11 hours *Irbesartan 11–15 hours *Olmesartan 13 hours *Telmisartan 24 hours *Fimasartan 7–11 hours
Angiotensin II receptor blocker
Calcium channel blocker
ACE inhibitor
Adrenergic blocking agent
SGLT2 inhibitor
Mercurial diuretic
Lipid-lowering agent
Adenosine receptor antagonist