This class of drugs is usually well tolerated. Common adverse drug reactions (ADRs) include: dizziness, headache, and/or hyperkalemia. 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. A 2014 Cochrane systematic review based on randomized controlled trials reported that when comparing patients taking ACE inhibitors to patients taking<unk> s, fewer<unk>  patients withdrew from the study due to adverse events compared to ACE inhibitor patients. 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. In addition, there is also a small risk of cross-reactivity in patients having experienced angioedema with ACE inhibitor therapy. Myocardial infarction The issue of whether<unk> <unk><unk>  antagonists slightly increase the risk of myocardial infarction (MI or heart attack) is currently being investigated. Some studies suggest<unk> s can increase the risk of MI. However, other studies have found<unk> s do not increase the risk of MI. To date, with no consensus on whether<unk> s have a tendency to increase the risk of myocardial infarction, further investigations are underway. Indeed, as a consequence of AT1 blockade,<unk> s increase<unk> <unk>  levels several-fold above baseline by uncoupling a negative-feedback loop. Increased levels of circulating<unk> <unk>  result in unopposed stimulation of the AT2<unk> s, which are, in addition, upregulated. However, recent data suggest AT2<unk>  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. Cancer A study published in 2010 determined that "...meta-analysis of randomised controlled trials suggests that<unk> s are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation." A later meta-analysis by the U.S. Food and Drug Administration (FDA) of 31 randomized controlled trials comparing<unk> s to other treatment found no evidence of an increased risk of incident (new) cancer, cancer-related death, breast cancer, lung cancer, or prostate cancer in patients receiving<unk> s. In 2013, comparative effectiveness research from the United States Department of Veterans Affairs on the experience of more than a million Veterans found no increased risks for either lung cancer (original article in Journal of Hypertension) or prostate cancer. 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<unk> s compared with nonusers. Our findings were consistent with a protective effect of<unk> s." 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<unk>  patients, compared with patients taking a placebo or other drugs. One of the criticisms Marciniak made was that the earlier FDA meta-analysis did not count lung carcinomas as cancers. In ten of the eleven studies he examined, Marciniak said that there were more lung cancer cases in the<unk>  group than the control group. 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." In an article about the dispute, the Wall Street Journal interviewed three other doctors to get their views; one had "no doubt"<unk> s increased cancer risk, one was concerned and wanted to see more data, and the third thought there was either no relationship or a hard to detect, low-frequency relationship. A 2016 meta-analysis including 148,334 patients found no significant differences in cancer incidence associated with<unk>  use. Kidney failure Although<unk> s have protective effects against developing kidney diseases for patients with diabetes and previous hypertension without administration of<unk> s,<unk> s may worsen kidney functions such as reducing glomerular filtration rate associated with a rise of serum creatinine in patients with pre-existing proteinuria, renal artery stenosis, hypertensive nephrosclerosis, heart failure, polycystic kidney disease, chronic kidney disease, interstitial fibrosis, focal segmental glomerulosclerosis, or any conditions such as<unk> s-treated but still clinically present hypertension that lead to abnormal narrowing of blood vessels to the kidney that interrupts oxygen and nutrient supply to the organ.
Angiotensin II receptor blocker
Calcium channel blocker
ACE inhibitor
Adrenergic blocking agent
SGLT2 inhibitor
Mercurial diuretic
Lipid-lowering agent
Adenosine receptor antagonist