Angiotensin II receptor blocker
[4] ARBs and the similar-attributed ACE inhibitors are both indicated as the first-line antihypertensives in patients developing hypertension along with left-sided heart failure.
[6][7] They do not inhibit the breakdown of bradykinin or other kinins, and are thus only rarely associated with the persistent dry cough and/or angioedema that limit ACE inhibitor therapy.
[citation needed] More recently, they have been used for the treatment of heart failure in patients intolerant of ACE inhibitor therapy, in particular candesartan.
Infrequent ADRs associated with therapy include: first dose orthostatic hypotension, rash, diarrhea, dyspepsia, abnormal liver function, muscle cramp, myalgia, back pain, insomnia, decreased hemoglobin levels, renal impairment, pharyngitis, and/or nasal congestion.
[20] While one of the main rationales for the use of this class is the avoidance of a persistent dry cough and/or angioedema associated with ACE inhibitor therapy, rarely they may still occur.
[19] The issue of whether angiotensin II receptor antagonists slightly increase the risk of myocardial infarction (MI or heart attack) is currently being investigated.
[needs update] Indeed, as a consequence of AT1 blockade, ARBs increase angiotensin II levels several-fold above baseline by uncoupling a negative-feedback loop.
However, recent data suggest AT2 receptor stimulation may be less beneficial than previously proposed, and may even be harmful under certain circumstances through mediation of growth promotion, fibrosis, and hypertrophy, as well as eliciting proatherogenic and proinflammatory effects.
[23][24][25] A study published in 2010 determined that "...meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis.
[29] The researchers concluded: "In this large nationwide cohort of United States Veterans, we found no evidence to support any concern of increased risk of lung cancer among new users of ARBs compared with nonusers.
"[28] In May 2013, a senior regulator at the Food & Drug Administration, Medical Team Leader Thomas A. Marciniak, revealed publicly that contrary to the FDA's official conclusion that there was no increased cancer risk, after a patient-by-patient examination of the available FDA data he had concluded that there was a lung-cancer risk increase of about 24% in ARB patients, compared with patients taking a placebo or other drugs.
Ellis Unger, chief of the drug-evaluation division that includes Marciniak, was quoted as calling the complaints a "diversion," and saying in an interview, "We have no reason to tell the public anything new."
[33][34][35][36][37][38][32][excessive citations] Losartan, irbesartan, olmesartan, candesartan, valsartan, fimasartan include the tetrazole group (a ring with four nitrogen and one carbon).
[citation needed] The specific efficacy of each ARB 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.
[75] These sartan medicines have a specific ring structure (tetrazole) whose synthesis could potentially lead to the formation of nitrosamine impurities.
[77] In April 2021, the European Directorate for the Quality of Medicines (EDQM) warned of the risk of contamination with non-nitrosamine impurities (specifically, azido compounds) in tetrazole-containing sartans.
[79] Later in 2021 and 2022, several cases of contamination with azido impurities were detected in losartan, irbesartan, and valsartan, prompting regulatory responses ranging from investigation to market withdrawals and precautionary recalls in Australia,[80] Brazil,[81] and Europe (including Switzerland).
