Editing ACE inhibitor (section)

==Adverse effects==
Common side effects include: low blood pressure, [[cough]], [[hyperkalemia]], [[headache]], [[Vertigo (medical)|dizziness]], [[Fatigue (physical)|fatigue]], [[nausea]], and [[kidney]] impairment.<ref name="AMH2006">{{cite book | vauthors = Rossi S | title = [[Australian Medicines Handbook]] | date = 2006 | location = Adelaide | publisher = Australian Medicines Handbook | isbn = 0-9757919-2-3}} {{Page needed|date=September 2010}}</ref><ref name="Sidorenkov & Navis 2014">{{cite journal | vauthors = Sidorenkov G, Navis G | title = Safety of ACE inhibitor therapies in patients with chronic kidney disease | journal = Expert Opinion on Drug Safety | volume = 13 | issue = 10 | pages = 1383–1395 | date = October 2014 | pmid = 25148900 | doi = 10.1517/14740338.2014.951328 | s2cid = 207488068 }}</ref>

The main adverse effects of ACE inhibition can be understood from their pharmacological action. The other reported adverse effects are liver problems and effects on the fetus.<ref name="Sidorenkov & Navis 2014"/> Kidney problems may occur with all ACE inhibitors that directly follows from their mechanism of action. Patients starting on an ACE inhibitor usually have a modest reduction in [[glomerular filtration rate]] (GFR).<ref name="Tucker Perazella 2019 pp. 78–83">{{cite book | vauthors = Tucker BM, Perazella MA | title=Nephrology Secrets | chapter=Medications: 3. What are the major adverse effects on the kidney of ACE inhibitors and ARBs? | publisher=Elsevier | year=2019 | isbn=978-0-323-47871-7 | doi=10.1016/b978-0-323-47871-7.00019-8 | pages=78–83 | s2cid=239423283 | quote=due to inhibition of angiotensin II production by ACE inhibitors or competitive antagonism of the angiotensin II receptor by ARBs... results in loss of angiotensin II–induced efferent arteriolar tone, leading to a drop in glomerular filtration fraction and GFR. The efferent arteriolal vasodilation reduces intraglomerular hypertension (and pressure-related injury) and maintains perfusion (and oxygenation) of the peritubular capillaries.}}</ref> However, the decrease may be significant in conditions of ''pre-existing'' decreased renal perfusions, such as renal artery stenosis, heart failure, polycystic kidney disease, or volume depletion. In these patients, the maintenance of GFR depends on angiotensin-II-dependent efferent vasomotor tone.<ref name="Tucker Perazella 2019 pp. 78–83"/> Therefore, [[renal function]] should be closely monitored over the first few days after initiation of treatment with ACE inhibitor in patients with decreased renal perfusion.<ref name="Sidorenkov & Navis 2014"/> Generally, a moderate reduction in renal function (no greater than 30% rise in serum [[creatinine]] which stabilizes within 2-4 weeks) is considered acceptable as part of the therapeutic effect.<ref>{{cite journal | vauthors = Bakris GL, Weir MR | title = Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? | journal = Archives of Internal Medicine | volume = 160 | issue = 5 | pages = 685–693 | date = March 2000 | pmid = 10724055 | doi = 10.1001/archinte.160.5.685 }}</ref><ref>{{cite journal | vauthors = Ohkuma T, Jun M, Rodgers A, Cooper ME, Glasziou P, Hamet P, Harrap S, Mancia G, Marre M, Neal B, Perkovic V, Poulter N, Williams B, Zoungas S, Chalmers J, Woodward M | title = Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus | journal = Hypertension | volume = 73 | issue = 1 | pages = 84–91 | date = January 2019 | pmid = 30571562 | doi = 10.1161/HYPERTENSIONAHA.118.12060 }}</ref>

Reduced GFR is especially a problem if the patient is concomitantly taking an [[Non-steroidal anti-inflammatory drug|NSAID]] and a [[diuretic]].<ref name="Byrd Ram Lerma 2019 pp. 477–482 II"/> When the three drugs are taken together,  the risk of developing renal failure is significantly increased.<ref name="Thomas2000">{{cite journal | vauthors = Thomas MC | title = Diuretics, ACE inhibitors and NSAIDs--the triple whammy | journal = The Medical Journal of Australia | volume = 172 | issue = 4 | pages = 184–185 | date = February 2000 | pmid = 10772593 | doi = 10.5694/j.1326-5377.2000.tb125548.x | s2cid = 37558579 }}</ref>

[[Hyperkalemia|High blood potassium]] is another possible complication of treatment with an ACE inhibitor due to its effect on aldosterone. Suppression of angiotensin II leads to a decrease in aldosterone levels. Since aldosterone is responsible for increasing the excretion of potassium, ACE inhibitors can cause retention of potassium. Some people, however, can continue to lose potassium while on an ACE inhibitor.<ref name="Cohn2000">{{cite journal | vauthors = Cohn JN, Kowey PR, Whelton PK, Prisant LM | title = New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice | journal = Archives of Internal Medicine | volume = 160 | issue = 16 | pages = 2429–2436 | date = September 2000 | pmid = 10979053 | doi = 10.1001/archinte.160.16.2429 | doi-access = free }}</ref> Hyperkalemia may decrease the velocity of impulse conduction in the nerves and muscles, including cardiac tissues. This leads to cardiac dysfunction and neuromuscular consequences, such as muscle weakness, paresthesia, nausea, diarrhea, and others. Close monitoring of potassium levels is required in patients receiving treatment with ACE inhibitors who are at risk of hyperkalemia.<ref name="Sidorenkov & Navis 2014"/>

Another possible adverse effect specific for ACE inhibitors, but not for other RAAS blockers, is an increase in [[bradykinin]] level.<ref name="Sidorenkov & Navis 2014"/>

A persistent dry cough is a relatively common adverse effect believed to be associated with the increases in bradykinin levels produced by ACE inhibitors, although the role of bradykinin in producing these symptoms has been disputed.<ref name="Okumura2001">{{cite journal | vauthors = Okumura H, Nishimura E, Kariya S, Ohtani M, Uchino K, Fukatsu T, Odanaka J, Takahashi T, Watanabe K, Itoh T, Hashiguchi M, Echizen H, Rikihisa T | title = [No relation between angiotensin-converting enzyme (ACE) inhibitor-induced cough and ACE gene polymorphism, plasma bradykinin, substance P and ACE inhibitor concentration in Japanese patients] | journal = Yakugaku Zasshi | volume = 121 | issue = 3 | pages = 253–257 | date = March 2001 | pmid = 11265121 | doi = 10.1248/yakushi.121.253 | doi-access = free }}</ref> Many cases of cough in people on ACE inhibitors may not be from the medication itself, however.<ref>{{cite journal | vauthors = Vukadinović D, Vukadinović AN, Lavall D, Laufs U, Wagenpfeil S, Böhm M | title = Rate of Cough During Treatment With Angiotensin-Converting Enzyme Inhibitors: A Meta-Analysis of Randomized Placebo-Controlled Trials | journal = Clinical Pharmacology and Therapeutics | volume = 105 | issue = 3 | pages = 652–660 | date = March 2019 | pmid = 29330882 | doi = 10.1002/cpt.1018 | s2cid = 46779755 }}</ref> People who experience this cough are often switched to [[angiotensin II receptor antagonist]]s.{{citation needed|date=August 2024}}

Some (0.7%)<ref name="Byrd Ram Lerma 2019 pp. 477–482 II"/> develop [[angioedema]] due to increased bradykinin levels.<ref>{{cite journal | vauthors = Bezalel S, Mahlab-Guri K, Asher I, Werner B, Sthoeger ZM | title = Angiotensin-converting enzyme inhibitor-induced angioedema | journal = The American Journal of Medicine | volume = 128 | issue = 2 | pages = 120–125 | date = February 2015 | pmid = 25058867 | doi = 10.1016/j.amjmed.2014.07.011 }}</ref> A genetic predisposition may exist.<ref name="Molinaro2002">{{cite journal | vauthors = Molinaro G, Cugno M, Perez M, Lepage Y, Gervais N, Agostoni A, Adam A | title = Angiotensin-converting enzyme inhibitor-associated angioedema is characterized by a slower degradation of des-arginine(9)-bradykinin | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 303 | issue = 1 | pages = 232–237 | date = October 2002 | pmid = 12235256 | doi = 10.1124/jpet.102.038067 | s2cid = 13866090 | hdl = 2434/161106 | hdl-access = free }}</ref>

A severe rare allergic reaction can affect the bowel wall and secondarily cause abdominal pain.<ref>{{cite journal | vauthors = Augenstein VA, Heniford BT, Sing RF | title = Intestinal angioedema induced by angiotensin-converting enzyme inhibitors: an underrecognized cause of abdominal pain? | journal = The Journal of the American Osteopathic Association | volume = 113 | issue = 3 | pages = 221–223 | date = March 2013 | pmid = 23485983 }}</ref>

===Blood===
Hematologic effects, such as neutropenia, agranulocytosis and other blood dyscrasias, have occurred during therapy with ACE inhibitors, especially in people with additional risk factors.<ref>FDA Prescribing information, http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20%28General%20Monographs-%20A%29/ACE%20INHIBITORS.html</ref>

===Pregnancy===
In pregnant women, ACE inhibitors taken during all the trimesters have been reported to cause [[congenital malformations]], [[stillbirth]]s, and [[neonatal death]]s. Commonly reported fetal abnormalities include [[hypotension]], [[renal dysplasia]], anuria/oliguria, [[oligohydramnios]], [[intrauterine growth retardation]], [[pulmonary hypoplasia]], [[patent ductus arteriosus]], and incomplete ossification of the skull.<ref name="Sidorenkov & Navis 2014"/><ref name="pmid9520613">{{cite journal | vauthors = Sørensen AM, Christensen S, Jonassen TE, Andersen D, Petersen JS | title = [Teratogenic effects of ACE-inhibitors and angiotensin II receptor antagonists] | language = da | journal = Ugeskrift for Laeger | volume = 160 | issue = 10 | pages = 1460–1464 | date = March 1998 | pmid = 9520613 }}</ref> Overall, about half of newborns exposed to ACE inhibitors are adversely affected, leading to [[birth defect]]s.<ref>{{cite journal | vauthors = Bullo M, Tschumi S, Bucher BS, Bianchetti MG, Simonetti GD | title = Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review | journal = Hypertension | volume = 60 | issue = 2 | pages = 444–450 | date = August 2012 | pmid = 22753220 | doi = 10.1161/HYPERTENSIONAHA.112.196352 | doi-access = free }}</ref><ref name="Byrd Ram Lerma 2019 pp. 477–482 II"/>

ACE inhibitors are [[Australian Drug Evaluation Committee|ADEC]] [[pregnancy category]] D and should be avoided in women who are likely to become pregnant.<ref name="AMH2006" /> In the U.S., ACE inhibitors must be labeled with a [[boxed warning]] concerning the risk of birth defects when taken during the second and third trimester. Their use in the first trimester is also associated with a risk of major [[congenital malformation]]s, particularly affecting the [[Circulatory system|cardiovascular]] and [[central nervous system]]s.<ref name="Cooper2006">{{cite journal | vauthors = Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA | title = Major congenital malformations after first-trimester exposure to ACE inhibitors | journal = The New England Journal of Medicine | volume = 354 | issue = 23 | pages = 2443–2451 | date = June 2006 | pmid = 16760444 | doi = 10.1056/NEJMoa055202 | doi-access = free }}</ref>