ACE inhibitors ACE inhibitors should be used with caution in people with: Impaired renal function Aortic valve stenosis or cardiac outflow obstruction Hypovolemia or dehydration Hemodialysis with high-flux polyacrylonitrile membranes A combination of ACE inhibitor with other drugs may increase effects of these drugs, but also the risk of adverse effects. The commonly reported adverse effects of drug combination with ACE inhibitor are acute renal failure, hypotension, and hyperkalemia. The drugs interacting with ACE inhibitor should be prescribed with caution. Special attention should be given to combinations of ACE inhibitor with other RAAS blockers, diuretics (especially potassium-sparing diuretics), NSAIDs, anticoagulants, cyclosporine, DPP-4 inhibitors, and potassium supplements. Potassium supplementation should be used with caution and under medical supervision owing to the hyperkalemic effect of ACE inhibitors. Concomitant use with cyclooxygenase inhibitors tends to decrease ACE inhibitor's hypotensive effect. Mechanism of action ACE inhibitors reduce the activity of the renin–angiotensin–aldosterone system (RAAS) as the primary etiologic (causal) event in the development of hypertension in people with diabetes mellitus, as part of the insulin-resistance syndrome or as a manifestation of renal disease. Renin–angiotensin–aldosterone system The renin–angiotensin–aldosterone system is a major blood pressure regulating mechanism. Markers of electrolyte and water imbalance in the body such as hypotension, low distal tubule sodium concentration, decreased blood volume and high sympathetic tone trigger the release of the enzyme renin from the cells of juxtaglomerular apparatus in the kidney. Renin activates a circulating liver derived prohormone angiotensinogen by proteolytic cleavage of all but its first ten amino acid residues known as angiotensin I. ACE (angiotensin converting enzyme) then removes a further two residues, converting angiotensin I into angiotensin II. ACE is found in the pulmonary circulation and in the endothelium of many blood vessels. The system increases blood pressure by increasing the amount of salt and water the body retains, although angiotensin is also very good at causing the blood vessels to tighten (a potent vasoconstrictor). Effects ACE inhibitors block the conversion of angiotensin I (ATI) to angiotensin II (ATII). They thereby lower arteriolar resistance and increase venous capacity; decrease cardiac output, cardiac index, stroke work, and volume; lower resistance in blood vessels in the kidneys; and lead to increased natriuresis (excretion of sodium in the urine). Renin increases in concentration in the blood as a result of negative feedback of conversion of ATI to ATII. ATI increases for the same reason; ATII and aldosterone decrease. Bradykinin increases