Angiotensin II
Identification
- Name
- Angiotensin II
- Accession Number
- DB11842
- Description
Angiotensin II is under investigation for the treatment of Sepsis, Septic Shock, Diabetes Mellitus, and Acute Renal Failure. Angiotensin II has been investigated for the treatment, basic science, and diagnostic of Hypertension, Renin Angiotensin System, and Idiopathic Membranous Nephropathy.
As of December 21, 2017 the FDA approved La Jolla Pharmaceutical's Giapreza (angiotensin II) Injection for Intravenouse Infusion for the indication of acting as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. The novelty of the medication lies in the fact that it is the first and only use of synthetic human angiotensin II to help maintain body blood pressure.
Shock is the inability to maintain blood flow to vital tissues and the potential resultant organ failure and death within hours, no matter young or o ld. As distributive shock is the most common type of shock in the inpatient setting and affects up to one third of patients in the intensive care unit, the FDA determined that there is a need for treatment options for critically ill hypotensive patients who do not adequately respond to currently available therapies.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 1046.1786
Monoisotopic: 1045.534514801 - Chemical Formula
- C50H71N13O12
- Synonyms
- 5-isoleucine-angiotensin II
- 5-L-isoleucineangiotensin II
- Angiotensin
- Angiotensin II
- Angiotensin II (human)
- Angiotonin
- Human angiotensin II
- Hypertensin
- Ile5-angiotensin II
- isoleucine5-angiotensin II
Pharmacology
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- Indication
Angiotensin II is a vasoconstrictor indicated for increasing blood pressure in adults with septic or other distributive shock Label.
- Associated Conditions
- Contraindications & Blackbox Warnings
- Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
- Pharmacodynamics
Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone-system (RAAS) that has the capacity to cause vasoconstriction and an increase in blood pressure in the human body. Label
In the RAAS, juxtaglomerular cells of the renal afferent arteriole synthesize the proteolytic enzyme renin. Although stored in an inactive form called pro-renin, decreases in arterial blood pressure or extracellular fluid volume depletion can cause various enzymatic reactions to release active renin into the systemic circulation and surrounding tissues. Such renin release allows for the production of the alpha-2-globulin angiotensinogen predominantly in the liver and to some extent, the kidneys and other organs. 1
Angiotensin I, itself a decapeptide with weak biological activity, is produced from angiotensinogen and then quickly converted to angiotensin II by angiotensin converting enzymes (ACE). Consequently, angiotensin II demonstrates its strong vasopressor activity when it is rapidly degraded by aminopeptidases A and M into further entities like angiotensin III and angiotensin IV, respectively. Such species like angiotensin III can then bind and interact with specific G protein coupled receptors like angiotensin receptor 1, or AT-1 1 where strong vasoconstricson can occur. 1
Furthermore, in the ATHOS-3 clinical trial, for the 114 (70%) patient subjects in the angiotensin II arm who reached the target mean arterial pressure (MAP) at Hour 3, the median time to reach the target MAP endpoint was approximately 5 minutes. The angiotensin II was titrated to effect for each individual patient. Label.
- Mechanism of action
As part of the renin-angiotensin-aldosterone-system (RAAS), angiotensin II raises blood pressure by vasoconstriction, increased aldosterone release by the adrenal zona glomerulosa, sodium and water reabsorption in the proximal tubular cells, and vasopressin secretion Label,1
The direct action of angiotensin II on surrounding vessel walls is facilitated by binding to the G-protein-coupled angiotensin II receptor type 1 (AT-1) on vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction that results in vasoconstriction Label,1.
The RAAS is ultimately regulated by a negative feedback effect of angiotensin II on renin production by the juxtaglomerular cells of the renal afferent arteriole. Unresuscitated septic shock associated with marked hypovolemia, extracellular fluid volume depletion, decreased cardiac output, low arterial blood pressure and decreased systemic vascular resistance causes an increase in renin secretion by the juxtaglomerular cells, resulting in elevated angiotensin II plasma levels and an increased secretion of aldosterone from the adrenal cortex. Angiotensin II binding to AT-1 receptors causes dose-dependent vasoconstriction of both afferent and efferent glomerular arterioles. The most pronounced effect of angiotensin II results on efferent arterioles, resulting in reduced renal blood flow and increased glomerular filtration pressure. 1
Target Actions Organism AType-1 angiotensin II receptor agonistHumans - Absorption
Following the intravenous infusion of angiotensin II in adult patients with septic or other distributive shock, the serum levels of angiotensin II observed were similar at baseline and hour 3 after the intravenous infusion. After 3 hours of treatment, the serum level of angiotensin I (the angiotensin II precursos peptide) is however, reduced by about 40% Label.
- Volume of distribution
The official prescribing information for angiotensin II notes that no specific studies have yet been conducted that examine the distribution of angiotensin II Label.
- Protein binding
- Not Available
- Metabolism
It is metabolized by aminopeptidase A and angiotensin converting enzyme 2 to angiotensin-(2-8) [angiotensin III] and angiotensin-(1-7), respectively in plasma, erythrocytes and many of the major organs (i.e. intestine, kidney, liver and lung). Angiotensin II type 1 receptor (AT1) mediated activity of angiotensin III is approximately 40% of angiotensin II; however, aldosterone synthesis activity is similar to angiotensin II. Angiotensin-(1-7) exerts the opposite effects of angiotensin II on AT1 receptors and causes vasodilation Label.
Nevertheless, the official prescribing information also notes that no formal studies have been conducted that examine the metabolism of angiotensin II Label.
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- Route of elimination
The official prescribing information notes that no specific studies have been conducted that examine the elimination of angiotensin II.
- Half-life
The plasma half-life of intravenously administered angiotensin II is less than one minute Label.
- Clearance
The official prescribing information notes that the clearnace of angiotensin II is not dependent on hepatic function or renal function Label.
- Adverse Effects
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- Toxicity
Overdose with angiotensin II would be expected to result in hypertension, necessitating close monitoring and supportive care Label. Effects are also expected to be brief as the half-life of angiotensin II is less than one minute Label.
In the ATHOS-3 clinical study there was a higher incidence of arterial and venous thrombotic and thromboembolic events in patients who received angiotensin II compared to placebo treated patients. The major imbalance was in deep venous thromboses - which prompts the potential need to use concurrent venous thromboembolism (VTE) prohphylaxis Label.
Adverse effects of noticeable potential (>= 10%) include thromboembolic events (ie. like deep vein thrombosis) including arterial and venous thrombotic events, thrombocytopenia, tachycardia, and fungal infection. Effects whose potential are < 10% include delirium, acidosis, hyperglycemia, peripheral ischemia Label.
Concomitant use of angiotensin converting enzymes (ACE) inhibitors may increase the response of angiotensin II Label.
Concomitant use of angiotensin II blockers (ARBs) may decrease the response to angiotensin II Label.
There are no formal data regarding the safe use of angiotensin II in pregnant women. However, septic or other distributive shock is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic or otherdistributive shock is likely to increase the risk of maternal and fetal morbidity and mortality Label.
There is no formal data regarding whether or not angiotensin II may become present in human milk and there is no data available on the effects of angiotensin II on the breastfed child or the effects on milk production Label.
The safety and efficacy of angiotensin II in pediatric patients has not yet been established Label.
There is no difference in the safety or efficacy between patients less than 65 years old and those 65 years or older when treated with angiotensin II Label.
There is no difference in pharmacokinetics between male and female patients Label.
The pharmacokinetics of angiotensin II are not expected to be influenced by renal impairment or hepatic impairment Label.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareLevothyroxine Levothyroxine may increase the vasoconstricting activities of Angiotensin II. Lidocaine The risk or severity of hypertension can be increased when Angiotensin II is combined with Lidocaine. Liothyronine Liothyronine may increase the vasoconstricting activities of Angiotensin II. Liotrix Liotrix may increase the vasoconstricting activities of Angiotensin II. Oxytocin The risk or severity of hypertension can be increased when Angiotensin II is combined with Oxytocin. Patent Blue The risk or severity of hypotension can be increased when Patent Blue is combined with Angiotensin II. Thyroid, porcine Thyroid, porcine may increase the vasoconstricting activities of Angiotensin II. Thyrotropin alfa Thyrotropin alfa may increase the vasoconstricting activities of Angiotensin II. Improve patient outcomesBuild effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.Learn more - Food Interactions
- No interactions found.
Products
- Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets
- Product Ingredients
Ingredient UNII CAS InChI Key Angiotensin II acetate 31L3HS630A 32044-01-2 VBTZKFAHKJXHBA-PIONDTTLSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Giapreza Injection, solution, concentrate 2.5 mg/ml Intravenous La Jolla Pharmaceutical Ii B.V. 2021-01-12 Not applicable EU Giapreza Injection, solution, concentrate 2.5 mg/ml Intravenous La Jolla Pharmaceutical Ii B.V. 2021-01-12 Not applicable EU Giapreza Injection 2.5 mg/1mL Intravenous La Jolla Pharmaceutical Company 2018-02-05 Not applicable US
Categories
- ATC Codes
- C01CX09 — Angiotensin ii
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Angiotensin II, antagonists & inhibitors
- Angiotensins
- Autacoids
- Biological Factors
- Cardiac Stimulants Excl. Cardiac Glycosides
- Cardiac Therapy
- Cardiovascular Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Inflammation Mediators
- Nerve Tissue Proteins
- Neuropeptides
- Oligopeptides
- Peptide Hormones
- Peptides
- Proteins
- Vasoconstriction
- Vasoconstrictor Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Oligopeptides
- Alternative Parents
- Tyrosine and derivatives / Phenylalanine and derivatives / Histidine and derivatives / Aspartic acid and derivatives / Isoleucine and derivatives / Valine and derivatives / Proline and derivatives / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Phenylpropanoic acids show 21 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 3-phenylpropanoic-acid / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid / Amino acid or derivatives / Amphetamine or derivatives / Aromatic heteromonocyclic compound show 46 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- angiotensin II (CHEBI:2719) / Angiotensin [KO:K09821] (C02135)
Chemical Identifiers
- UNII
- M089EFU921
- CAS number
- 4474-91-3
- InChI Key
- CZGUSIXMZVURDU-JZXHSEFVSA-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
- IUPAC Name
- (3S)-3-amino-3-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S,2S)-1-{[(2S)-1-[(2S)-2-{[(1S)-1-carboxy-2-phenylethyl]carbamoyl}pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl}-2-methylbutyl]carbamoyl}-2-(4-hydroxyphenyl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}-4-[(diaminomethylidene)amino]butyl]carbamoyl}propanoic acid
- SMILES
- CC[C@H](C)[C@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O
References
- General References
- Correa TD, Takala J, Jakob SM: Angiotensin II in septic shock. Crit Care. 2015 Mar 16;19:98. doi: 10.1186/s13054-015-0802-3. [PubMed:25886853]
- External Links
- Human Metabolome Database
- HMDB0001035
- KEGG Compound
- C02135
- PubChem Compound
- 172198
- PubChem Substance
- 347828186
- ChemSpider
- 150504
- BindingDB
- 50236697
- 1999003
- ChEBI
- 58506
- ChEMBL
- CHEMBL408403
- ZINC
- ZINC000169676920
- Wikipedia
- Angiotensin
- FDA label
- Download (2.45 MB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Prevention High Blood Pressure (Hypertension) / Stroke / Transient Ischemic Attack 1 4 Completed Diagnostic High Blood Pressure (Hypertension) 1 4 Completed Other Dyslipidemia / High Blood Pressure (Hypertension) 1 4 Completed Prevention Cardiovascular Disease (CVD) 1 4 Completed Prevention High Blood Pressure (Hypertension) / Infarction, Brain 1 4 Completed Prevention Kidney Stones 1 4 Completed Treatment Body Composition / Exercise Tolerance / Heart Failure / Strength, Muscle / Vasodilation 1 4 Completed Treatment Diabetic Nephropathy / Persistent Proteinuria With Type II Diabetes 1 4 Completed Treatment High Blood Pressure (Hypertension) 1 4 Completed Treatment High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 2.5 mg/1mL Injection, solution, concentrate Intravenous 2.5 MG/ML Injection, solution, concentrate Intravenous 5 MG/ML - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9572856 No 2017-02-21 2030-09-20 US US9220745 No 2015-12-29 2034-12-18 US US9867863 No 2018-01-16 2029-12-16 US US10028995 No 2018-07-24 2034-12-18 US US10335451 No 2019-07-02 2029-12-16 US US10493124 No 2019-12-03 2034-12-18 US US10500247 No 2019-12-10 2029-12-16 US US10548943 No 2009-12-16 2029-12-16 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0156 mg/mL ALOGPS logP -0.87 ALOGPS logP -5.3 ChemAxon logS -4.8 ALOGPS pKa (Strongest Acidic) 3.15 ChemAxon pKa (Strongest Basic) 10.83 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 17 ChemAxon Hydrogen Donor Count 13 ChemAxon Polar Surface Area 408.84 Å2 ChemAxon Rotatable Bond Count 29 ChemAxon Refractivity 269.81 m3·mol-1 ChemAxon Polarizability 107.02 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Protein heterodimerization activity
- Specific Function
- Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
- Gene Name
- AGTR1
- Uniprot ID
- P30556
- Uniprot Name
- Type-1 angiotensin II receptor
- Molecular Weight
- 41060.53 Da
Drug created on October 20, 2016 20:53 / Updated on February 21, 2021 18:53