Nesiritide, sold under the brand name Natrecor, is the
recombinant form of the 32 amino acid human
B-type natriuretic peptide, which is normally produced by the ventricular myocardium. Nesiritide works to facilitate
cardiovascular
In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...
fluid
homeostasis
In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...
through counterregulation of the
renin–angiotensin–aldosterone system, stimulating
cyclic guanosine monophosphate
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in ...
, leading to
smooth muscle
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
cell relaxation.
Nesiritide was believed initially to be beneficial for
acute decompensated congestive heart failure. It received approval from the United States'
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
for this purpose in 2001 after initial non-approval. In July 2011, the results of the largest study so far for nesiritide was published in ''
The New England Journal of Medicine
''The New England Journal of Medicine'' (''NEJM'') is a weekly medical journal published by the Massachusetts Medical Society. Founded in 1812, the journal is among the most prestigious peer-reviewed medical journals. Its 2023 impact factor w ...
''. The study failed to show a difference between nesiritide and placebo on mortality or re-hospitalizations.
Administration
Nesiritide is only administered
intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
ly, usually by
bolus, followed by IV infusion. For most adults and the
elderly
Old age is the range of ages for people nearing and surpassing life expectancy. People who are of old age are also referred to as: old people, elderly, elders, senior citizens, seniors or older adults. Old age is not a definite biological sta ...
, a normal dosage is 2
mg/kg followed by a continuous IV infusion of 0.01 mg/kg/min. This may be increased every three hours for a maximum of 0.03 mg/kg/min.
Controversy
In 2005, after several academic papers published by
Jonathan Sackner-Bernstein on the efficacy and side effects of nesiritide, Johnson & Johnson met with the FDA and altered its stated plans for the drug and agreed to revise its labeling.
Heart doctors at the
Cleveland Clinic
Cleveland Clinic is an American Nonprofit organization, nonprofit Academic health science center, academic Medical centers in the United States, medical center based in Cleveland, Ohio. Owned and operated by the Cleveland Clinic Foundation, an O ...
then voted unanimously not to permit the prescription of the drug to its patients.
Johnson and Johnson
Johnson & Johnson (J&J) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical, biotechnology, and Medical device, medical technologies corporation headquartered in New Brunswick, New Jersey, and publi ...
convened a panel of experts whose advice included the recommendation to conduct the large-scale clinical trial that was subsequently published in 2011. Following this, the
United States Department of Justice
The United States Department of Justice (DOJ), also known as the Justice Department, is a United States federal executive departments, federal executive department of the U.S. government that oversees the domestic enforcement of Law of the Unite ...
announced an inquiry into the marketing of the drug that led to a fine against the Scios unit of J&J.
Side effects
Common side effects include:
*
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 ...
(11% of patients)
*
Headache
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
*
Nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Over 30 d ...
*
Slow heart rate
Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due t ...
*
Kidney failure
Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
More rare side effects include:
*
Confusion
In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"
*
Paresthesia
Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...
*
Somnolence
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...
*
Tremor
A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...
References
Further reading
*
External links
Natrecor.com
{{Vasodilators used in cardiac diseases
Peptides
Drugs acting on the cardiovascular system
Drugs developed by Johnson & Johnson