Angiotensin II (medication)

Last updated

Angiotensin II
Angiotensin II.svg
Clinical data
Trade names Giapreza
AHFS/Drugs.com Monograph
Routes of
administration
Intravenous injection
Drug class Vasoconstrictor
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 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)
Identifiers
  • L-alpha-aspartyl-L-arginyl-L-valyl-L-tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C50H71N13O12
Molar mass 1046.197 g·mol−1
3D model (JSmol)
  • 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
  • InChI=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
  • Key: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 [3] 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. [4]

Contents

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. [5]

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. [6] [7] The vasopressor effects of angiotensin have been studied since it was first isolated in the late 1930s. [8] 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. [1]

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. [1]

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]

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<span class="mw-page-title-main">Shock (circulatory)</span> Medical condition of insufficient blood flow

Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thirst. This may be followed by confusion, unconsciousness, or cardiac arrest, as complications worsen.

<span class="mw-page-title-main">Sepsis</span> Life-threatening response to infection

Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs.

<span class="mw-page-title-main">Vasoconstriction</span> Narrowing of blood vessels due to the constriction of smooth muscle cells

Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in controlling hemorrhage and reducing acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased, thus retaining body heat or increasing vascular resistance. This makes the skin turn paler because less blood reaches the surface, reducing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates and maintains mean arterial pressure.

<span class="mw-page-title-main">Septic shock</span> Dangerously low blood pressure due to damage from an organ infection

Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by requiring a vasopressor to maintain a mean arterial pressure of 65 mm Hg or greater and having serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%.

<span class="mw-page-title-main">Vasodilation</span> Widening of blood vessels

Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.

<span class="mw-page-title-main">Hypotension</span> Abnormally low blood pressure

Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is indicated by two numbers, the systolic blood pressure and the diastolic blood pressure, which are the maximum and minimum blood pressures within the cardiac cycle, respectively. A systolic blood pressure of less than 90 millimeters of mercury (mmHg) or diastolic of less than 60 mmHg is generally considered to be hypotension. Different numbers apply to children. However, in practice, blood pressure is considered too low only if noticeable symptoms are present.

An inotrope or inotropic is a drug or any substance that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction.

<span class="mw-page-title-main">Pulmonary hypertension</span> Increased blood pressure in lung arteries

Pulmonary hypertension is a condition of increased blood pressure in the arteries of the lungs. Symptoms include shortness of breath, fainting, tiredness, chest pain, swelling of the legs, and a fast heartbeat. The condition may make it difficult to exercise. Onset is typically gradual. According to the definition at the 6th World Symposium of Pulmonary Hypertension in 2018, a patient is deemed to have pulmonary hypertension if the pulmonary mean arterial pressure is greater than 20mmHg at rest, revised down from a purely arbitrary 25mmHg, and pulmonary vascular resistance (PVR) greater than 3 Wood units.

<span class="mw-page-title-main">Hypovolemic shock</span> Medical condition

Hypovolemic shock is a form of shock caused by severe hypovolemia. It could be the result of severe dehydration through a variety of mechanisms or blood loss. Hypovolemic shock is a medical emergency; if left untreated, the insufficient blood flow can cause damage to organs, leading to multiple organ failure.

<span class="mw-page-title-main">Phenylephrine</span> Decongestant medication

Phenylephrine is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, or applied to the skin.

<span class="mw-page-title-main">Telmisartan</span> Blood pressure lowering medication

Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination telmisartan/hydrochlorothiazide, telmisartan/cilnidipine and telmisartan/amlodipine.

<span class="mw-page-title-main">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

Distributive shock is a medical condition in which abnormal distribution of blood flow in the smallest blood vessels results in inadequate supply of blood to the body's tissues and organs. It is one of four categories of shock, a condition where there is not enough oxygen-carrying blood to meet the metabolic needs of the cells which make up the body's tissues and organs. Distributive shock is different from the other three categories of shock in that it occurs even though the output of the heart is at or above a normal level. The most common cause is sepsis leading to a type of distributive shock called septic shock, a condition that can be fatal.

<span class="mw-page-title-main">Fenoldopam</span> Antihypertensive agent, also used in hypertensive crisis

Fenoldopam mesylate (Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist. Fenoldopam is used as an antihypertensive agent. It was approved by the Food and Drug Administration (FDA) in September 1997.

<span class="mw-page-title-main">Dopexamine</span> Chemical compound

Dopexamine is a synthetic analogue of dopamine that is administered intravenously in hospitals to reduce exacerbations of heart failure and to treat heart failure following cardiac surgery. It is not used often, as more established drugs like epinephrine, dopamine, dobutamine, norepinephrine, and levosimendan work as well. It works by stimulating beta-2 adrenergic receptors and peripheral dopamine receptor D1 and dopamine receptor D2. It also inhibits the neuronal re-uptake of norepinephrine.

<span class="mw-page-title-main">Norepinephrine (medication)</span> Therapeutic use of norepinephrine

Norepinephrine, also known as noradrenaline, is a medication used to treat people with very low blood pressure. It is the typical medication used in sepsis if low blood pressure does not improve following intravenous fluids. It is the same molecule as the hormone and neurotransmitter norepinephrine. It is given by slow injection into a vein.

<span class="mw-page-title-main">Vasopressin (medication)</span> Chemical compound

Vasopressin infusions are in use for septic shock patients not responding to fluid resuscitation or infusions of catecholamines to increase the blood pressure while sparing the use of catecholamines. These argipressins have much shorter elimination half-life than synthetic non-arginine vasopresines with much longer elimination half-life of many hours. Further, argipressins act on V1a, V1b, and V2 receptors which consequently lead to higher eGFR and lower vascular resistance in the lungs. A number of injectable arginine vasopressins are in clinical use in the United States and the European Union. Pitressin among others, is a medication most commonly used in the treatment of frequent urination, increased thirst, and dehydration such as that resulting from diabetes insipidus, which causes increased and diluted urine. It is used to treat abdominal distension following some surgeries, and in stomach roentgenography. Vasopressin is a hormone that affects the kidneys and reduces urine flow.

Vasodilatory shock, vasogenic shock, or vasoplegic shock is a medical emergency belonging to shock along with cardiogenic shock, septic shock, allergen-induced shock and hypovolemic shock. When the blood vessels suddenly relax, it results in vasodilation. In vasodilatory shock, the blood vessels are too relaxed leading to extreme vasodilation and blood pressure drops and blood flow becomes very low. Without enough blood pressure, blood and oxygen will not be pushed to reach the body's organs. If vasodilatory shock lasts more than a few minutes, the lack of oxygen starts to damage the body's organs. Vasodilatory shock like other types of shock should be treated quickly, otherwise it can cause permanent organ damage or death as a result of multiple organ dysfunction.

References

  1. 1 2 3 "Giapreza- angiotensin ii injection". DailyMed. 20 June 2020. Retrieved 17 September 2020.
  2. "Giapreza EPAR". European Medicines Agency. 23 August 2019. Retrieved 13 June 2024.
  3. Kaufman MB (March 2018). "Pharmaceutical Approval Update". P & T. 43 (3): 141–170. PMC   5821238 . PMID   29491694.
  4. "FDA approves drug to treat dangerously low blood pressure" (Press release). U.S. Food and Drug Administration (FDA). 21 December 2017.
  5. New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.
  6. Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, et al. (March 2013). "Survival after shock requiring high-dose vasopressor therapy". Chest. 143 (3): 664–671. doi:10.1378/chest.12-1106. PMC   3590882 . PMID   22911566.
  7. Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, et al. (October 2014). "Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study". Critical Care. 18 (5): 534. doi: 10.1186/s13054-014-0534-9 . PMC   4212099 . PMID   25286986.
  8. Bradley SE, Parker B (November 1941). "The Hemodynamic Effects of Angiotonin in Normal Man". The Journal of Clinical Investigation. 20 (6): 715–719. doi:10.1172/JCI101265. PMC   435102 . PMID   16694877.
  9. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. (August 2017). "Angiotensin II for the Treatment of Vasodilatory Shock". The New England Journal of Medicine. 377 (5): 419–430. doi: 10.1056/NEJMoa1704154 . hdl: 1959.13/1353018 . PMID   28528561. S2CID   205102054.
  10. Liaudet L, Calderari B, Pacher P (November 2014). "Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity" (PDF). Heart Failure Reviews. 19 (6): 815–824. doi:10.1007/s10741-014-9418-y. PMID   24398587. S2CID   22420796.