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
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
fluid
homeostasis
In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
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 r ...
, leading to
smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
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 respon ...
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. It is among the most prestigious peer-reviewed medical journals as well as the oldest continuously published one.
His ...
''. 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 nutrie ...
ly, usually by
bolus, followed by IV infusion. For most adults and the
elderly
Old age refers to ages nearing or surpassing the life expectancy of human beings, and is thus the end of the human life cycle. Terms and euphemisms for people at this age include old people, the elderly (worldwide usage), OAPs (British usage ...
, 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 a nonprofit American academic medical center based in Cleveland, Ohio. Owned and operated by the Cleveland Clinic Foundation, an Ohio nonprofit corporation established in 1921, it runs a 170-acre (69 ha) campus in Cleveland, ...
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 founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...
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 federal executive department of the United States government tasked with the enforcement of federal law and administration of justice in the United State ...
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 is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
(11% of patients)
*
Headache
Headache 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 in those with severe headaches.
Headaches can occur as a result ...
*
Nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
*
Slow heart rate
Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...
*
Kidney failure
Kidney failure, also known as end-stage kidney disease, 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 failure is classified as eit ...
More rare side effects include:
*
Confusion
In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
*
Paresthesia
Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
*
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 asleep ...
*
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
References
Further reading
*
External links
Natrecor.com
Peptides
Drugs acting on the cardiovascular system
Johnson & Johnson brands
{{cardiovascular-drug-stub