Angiotensin II (medication) explained

Drug Name:Angiotensin II
Tradename:Giapreza
Routes Of Administration:Intravenous injection
Class:Vasoconstrictor
Atc Prefix:C01
Atc Suffix:CX09
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Eu Comment:[1]
Protein Bound:None
Metabolism:Proteolysis by glutamyl aminopeptidase, angiotensin converting enzyme 2
Metabolites:Angiotensin III, angiotensin-(1-7)
Elimination Half-Life:Less than one minute (IV administration)
Index2 Label:as salt
Cas Number:4474-91-3
Pubchem:172198
Drugbank:DB11842
Unii:M089EFU921
Kegg:D02014
Kegg2:D11142
Chemspiderid:150504
Iupac Name:L-alpha-aspartyl-L-arginyl-L-valyl-L-tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine
C:50
H:71
N:13
O:12
Smiles:CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N
Stdinchi:InChI=1S/C50H71N13O12/c1-5-28(4)41(47(72)59-36(23-31-25-54-26-56-31)48(73)63-20-10-14-38(63)45(70)60-37(49(74)75)22-29-11-7-6-8-12-29)62-44(69)35(21-30-15-17-32(64)18-16-30)58-46(71)40(27(2)3)61-43(68)34(13-9-19-55-50(52)53)57-42(67)33(51)24-39(65)66/h6-8,11-12,15-18,25-28,33-38,40-41,64H,5,9-10,13-14,19-24,51H2,1-4H3,(H,54,56)(H,57,67)(H,58,71)(H,59,72)(H,60,70)(H,61,68)(H,62,69)(H,65,66)(H,74,75)(H4,52,53,55)/t28-,33-,34-,35-,36-,37-,38-,40-,41-/m0/s1
Stdinchikey:CZGUSIXMZVURDU-JZXHSEFVSA-N

Angiotensin II (Ang II) is a medication that is used to treat hypotension resulting from septic shock or other distributive shock. It is a synthetic vasoconstrictor peptide that is identical to human hormone angiotensin II[2] and is marketed under the brand name Giapreza. The Food and Drug Administration approved the use of angiotensin II in December 2017 to treat low blood pressure resulting from septic shock.[3]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[4]

Medical uses

Angiotensin II is a vasoconstrictor used to increase blood pressure in adults with septic or other distributive shock. Angiotensin II is a naturally occurring hormone secreted as part of the renin-angiotensin system that results in powerful systemic vasoconstriction.[5] [6] The vasopressor effects of angiotensin have been studied since it was first isolated in the late 1930s.[7] Vasopressors are defined as agents that combat vasodilatory shock by inducing peripheral vasoconstriction. Commonly used vasopressors include catecholamine (e.g., dopamine, norepinephrine, epinephrine) and non-catecholamine (e.g., vasopressin). but these agents are not always effective in reversing vasodilatory shock, and their use can be associated with significant side effects including limb ischemia and cardiac arrhythmia. Angiotensin II is as a treatment option that can increase blood pressure and allow catecholamine dose reductions.

Angiotensin II must be administered as an intravenous infusion diluted in 0.9% sodium chloride prior to use.[8]

Adverse effects

Angiotensin II treated patients are at an increased risk of thromboembolic events. There was a higher incidence of arterial and venous thrombotic and thromboembolic events in patients who received angiotensin II compared to placebo treated patients in the ATHOS-3 study [13% (21/163 patients) vs. 5% (8/158 patients)].[9] It is recommended that patients be on concurrent venous thromboembolism prophylaxis. Other adverse reactions include thrombocytopenia, tachycardia, fungal infection, delirium, acidosis, hyperglycemia, and peripheral ischemia.

Angiotensin II acts on angiotensin receptor (AT1) on presynaptic adrenergic nerves → release of catecholamine → excessive catecholamine can be harmful as it can cause myocyte necrosis.[10]

Notes and References

  1. Web site: Giapreza EPAR . European Medicines Agency . 23 August 2019 . 13 June 2024.
  2. Kaufman MB . Pharmaceutical Approval Update . P & T . 43 . 3 . 141–170 . March 2018 . 29491694 . 5821238 .
  3. FDA approves drug to treat dangerously low blood pressure . U.S. Food and Drug Administration (FDA) . 21 December 2017.
  4. New Drug Therapy Approvals 2017 . U.S. Food and Drug Administration (FDA) . January 2018 . PDF . 16 September 2020.
  5. Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, Miller RR, Hirshberg EL, Grissom CK, Morris AH . Survival after shock requiring high-dose vasopressor therapy . Chest . 143 . 3 . 664–671 . March 2013 . 22911566 . 3590882 . 10.1378/chest.12-1106 .
  6. Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG . Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study . Critical Care . 18 . 5 . 534 . October 2014 . 25286986 . 4212099 . 10.1186/s13054-014-0534-9 . free .
  7. Bradley SE, Parker B . The Hemodynamic Effects of Angiotonin in Normal Man . The Journal of Clinical Investigation . 20 . 6 . 715–719 . November 1941 . 16694877 . 435102 . 10.1172/JCI101265 .
  8. Web site: Giapreza- angiotensin ii injection . DailyMed . 20 June 2020 . 17 September 2020.
  9. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hästbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM . Angiotensin II for the Treatment of Vasodilatory Shock . The New England Journal of Medicine . 377 . 5 . 419–430 . August 2017 . 28528561 . 10.1056/NEJMoa1704154 . 205102054 . free . 1959.13/1353018 . free .
  10. Liaudet L, Calderari B, Pacher P . Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity . Heart Failure Reviews . 19 . 6 . 815–824 . November 2014 . 24398587 . 10.1007/s10741-014-9418-y . 22420796 .