| Primary information |
|---|
| ID | 1530 |
| ThPP ID | Th1109 |
| Therapeutic Peptide/Protein Name | Nesiritide |
| Sequence | SPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 3464 |
| Chemical Formula | N.A. |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Approx. 18 mins |
| Description | Recombinant, 32 amino acid human B-type natriuretic peptide, which is normally produced by the ventricular myocardium. Nesiritide is a medication used to treat acutely decompensated congestive heart failure with dyspnea at rest or with minimal exertion. |
| Indication/Disease | For the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity. |
| Pharmacodynamics | Nesiritide works to facilitate cardiovascular fluid homeostasis through counterregulation of the renin-angiotensin-aldoesterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle cell relaxation. In simpler terms, it promotes vasodilation, natriuresis, and diuresis. |
| Mechanism of Action | Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of guanosine 3'5'-cyclic monophosphate (cGMP) and smooth muscle cell relaxation. Cyclic GMP serves as a second messenger to dilate veins and arteries. Nesiritide has been shown to relax isolated human arterial and venous tissue preparations that were precontracted with either endothelin-1 or the alpha-adrenergic agonist, phenylephrine. In human studies, nesiritide produced dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure in patients with heart failure. In animals, nesiritide had no effects on cardiac contractility or on measures of cardiac electrophysiology such as atrial and ventricular effective refractory times or atrioventricular node conduction. Naturally occurring atrial natriuretic peptide (ANP), a related peptide, increases vascular permeability in animals and humans and may reduce intravascular volume. The effect of nesiritide on vascular permeability has not been studied.
|
| Toxicity | No data are available with respect to overdosage in humans. The expected reaction would be excessive hypotension, which should be treated with drug discontinuation or reduction and appropriate measures. |
| Metabolism | Nesiritide undergoes proteolytic cleavage of the peptide by endopeptidases, such as neutral endopeptidase, which are present on the vascular lumenal surface. |
| Absorption | Administration of nesiritide exhibits biphasic disposition from the plasma. |
| Volume of Distribution | 0.19 L/kg |
| Clearance | 9.2 mL/min/k [patients with congestive heart failure receiving IV infusion] |
| Categories | N.A. |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | NATRECOR |
| Company | Scios unit of Johnson & Johnson, |
| Brand Discription | NATRECOR (nesiritide) is a sterile, purified preparation of human B-type natriuretic peptide (hBNP), and is manufactured from E. coli using recombinant DNA technology. Nesiritide has a molecular weight of 3464 g/mol and an empirical formula of C143H244N50O42S4. Nesiritide has the same 32 amino acid sequence as the endogenous peptide, which is produced by the ventricular myocardiu |
| Prescribed for | NATRECOR (nesiritide) is indicated for the treatment of patients with acutely decompensated heart failure who have dyspnea at rest or with minimal activity. In this population, the use of NATRECOR reduced pulmonary capillary wedge pressure and improved short term (3 hours) symptoms of dyspnea. |
| Chemical Name | N.A. |
| Formulation | NATRECOR is formulated as the citrate salt of rhBNP, and is provided in a sterile, single-use vial. Each 1.5 mg vial contains a white- to off-white lyophilized powder for intravenous (IV) administration after reconstitution. The quantitative composition of the lyophilized drug per vial is: nesiritide 1.58 mg, citric acid monohydrate 2.1 mg, mannitol 20.0 mg, and sodium citrate dihydrate 2.94 mg |
| Physcial Appearance | White- to off-white lyophilized powde |
| Route of Administration | Intravenous |
| Recommended Dosage | IV bolus of 2 mcg/kg followed by a continuous infusion of 0.01 mcg/kg/min |
| Contraindication | NATRECOR is contraindicated in patients with: Persistent systolic blood pressure < 100 mm Hg prior to therapy because of an increased risk of symptomatic hypotension Known hypersensitivity to any of its components. |
| Side Effects | Hypotension |
| Useful Link | http://www.rxlist.com/natrecor-drug.htm https://en.wikipedia.org/wiki/Nesiritide http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=13531 http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm169897.htm |
| PubMed ID | 17826644, 12668889, 12549957, 12070532, 12028606 |
| 3-D Structure | N.A. |