Plecanatide
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Plecanatide
Plecanatide, sold under the brand name Trulance, is a medication for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. Plecanatide is an agonist of guanylate cyclase-C. Plecanatide increases intestinal transit and fluid through a buildup of cGMP. Medical uses As of January 2017, plecanatide is approved in the United States for the treatment of chronic idiopathic constipation in adults. The presence of this condition is determined using the Rome III diagnostic criteria for chronic constipation which requires that the patient meet stool frequency, stool consistency, incomplete evacuation, and straining requirements in addition to not being a likely candidate for irritable bowel syndrome. The symptoms should also have been present for at least three of the last six months to establish the chronic nature of the condition before treatment with plecanatide is indicated. Plecanatide has been shown to be safe and effective. It has s ...
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Linaclotide
Linaclotide, (sold under the brand name Linzess in the US and Mexico, and as Constella elsewhere) is a drug used to treat irritable bowel syndrome with constipation and chronic constipation with no known cause. For label updates seFDA index page for NDA 202811/ref> It has a black box warning about the risk of serious dehydration in children in the US; the most common adverse effects in others are gastrointestinal. It is an oligo-peptide agonist of guanylate cyclase 2C and remains in the GI tract after it is taken orally. It was approved in the US and Europe in 2012. It is marketed by Allergan in most of the world and by Astellas in Asia; Ironwood Pharmaceuticals was the originator. In 2020, it was the 244th most commonly prescribed medication in the United States, with more than 1million prescriptions. Medical use Linaclotide is used to treat irritable bowel syndrome with constipation and chronic constipation with no known cause. It has not been tested in pregnant women and it ...
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Guanylate Cyclase C
Guanylate cyclase 2C, also known as guanylyl cyclase C (GC-C), intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor (hSTAR) is an enzyme that in humans is encoded by the ''GUCY2C'' gene. Guanylyl cyclase is an enzyme found in the luminal aspect of intestinal epithelium and dopamine neurons in the brain.Intestinal Protein May Have Role in ADHD, Other Neurological Disorders. ScienceDaily (Aug. 11, 2011/ref> The receptor has an extracellular ligand-binding domain, a single transmembrane region, a region with sequence similar to that of protein kinases, and a C-terminal guanylate cyclase domain. Tyrosine kinase activity mediates the GC-C signaling pathway within the cell. Functions GC-C is a key receptor for heat-stable enterotoxins that are responsible for acute secretory diarrhea. Heat-stable enterotoxins are produced by pathogens such as ''Escherichia coli''. Knockout mice deficient in the GC-C gene do not show secretory diarrhe ...
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Chronic Idiopathic Constipation
Functional constipation, known as chronic idiopathic constipation (CIC), is constipation that does not have a physical (anatomical) or physiological (hormonal or other body chemistry) cause. It may have a neurological, psychological or psychosomatic cause. A person with functional constipation may be healthy, yet has difficulty defecating. Symptoms and diagnosis Chronic idiopathic constipation is similar to constipation-predominant irritable bowel syndrome (IBS-C); however, people with CIC do not have other symptoms of IBS, such as abdominal pain. Diagnosing CIC can be difficult as other syndromes must be ruled out as there is no physiological cause for CIC. Doctors will typically look for other symptoms, such as blood in stool, weight loss, low blood count, or other symptoms. To be considered functional constipation, symptoms must be present at least a fourth of the time. Possible causes are: * Anismus * Descending perineum syndrome * Other inability or unwillingness to contro ...
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Functional Constipation
Functional constipation, known as chronic idiopathic constipation (CIC), is constipation that does not have a physical (anatomical) or physiological (hormonal or other body chemistry) cause. It may have a neurological, psychological or psychosomatic A somatic symptom disorder, formerly known as a somatoform disorder,(2013) defecating Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging ...
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Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ...
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Health Canada
Health Canada (HC; french: Santé Canada, SC)Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary units, department of the Government of Canada responsible for national health policy. The department itself is also responsible for numerous federal health-related agencies, including the Canadian Food Inspection Agency (CFIA) and the Public Health Agency of Canada (PHAC), among others. These organizations help to ensure compliance with federal law in a variety of Healthcare in Canada, healthcare, Agriculture in Canada, agricultural, and Pharmaceutics, pharmaceutical activities. This responsibility also involves extensive collaboration with various other federal- and provincial-level organizations in order to ensure the safety of food, health, and Medication, pharmaceutical products—including the regulation of health research and pharmaceutic ...
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Medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management. Drugs are classified in multiple ways. One of the key divisions is by level of control, which distinguishes prescription drugs (those that a pharmacist dispenses only on the order of a physician, physician assistant, or qualified nurse) from over-the-counter drugs (those that consumers can order for themselves). Another key distinction is between traditional small molecule drugs, usually derived from chemical synthesis, and biopharmaceuticals, which include recombinant proteins, vaccines, blood products used therapeutically (such as IVIG), gene therapy, monoclonal antibodies and cell therapy (for instance, stem cell therapies) ...
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Irritable Bowel Syndrome
Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may occur over a long time, sometimes for years. IBS can negatively affect quality of life and may result in missed school or work (absenteeism) or reduced productivity at work (presenteeism). Disorders such as anxiety, major depression, and chronic fatigue syndrome are common among people with IBS.The cited review is based on sources ranging from 1988 to 2001 and is probably biased relative to a more recent research. The causes of IBS may well be multi-factorial. Theories include combinations of "gut–brain axis" problems, alterations in gut motility, visceral hypersensitivity, infections including small intestinal bacterial overgrowth, neurotransmitters, genetic factors, and food sensitivity. Onset may be triggered by an intestinal infec ...
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Agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist. Etymology From the Greek αγωνιστής (agōnistēs), contestant; champion; rival < αγων (agōn), contest, combat; exertion, struggle < αγω (agō), I lead, lead towards, conduct; drive


Types of agonists

can be activated by either endogenous agonists (such as

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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 response to the binding of membrane-impermeable peptide hormones to the external cell surface. Synthesis Guanylate cyclase (GC) catalyzes cGMP synthesis. This enzyme converts GTP to cGMP. Peptide hormones such as the atrial natriuretic factor activate membrane-bound GC, while soluble GC (sGC) is typically activated by nitric oxide to stimulate cGMP synthesis. sGC can be inhibited by ODQ (1H-,2,4xadiazolo ,3-auinoxalin-1-one). Functions cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles leads to vasodilation and increased blood flow. At presynaptic terminals in the striatum, cGMP controls the e ...
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Rome Process
The Rome process and Rome criteria are an international effort to create scientific data to help in the diagnosis and treatment of functional gastrointestinal disorders, such as irritable bowel syndrome, functional dyspepsia and rumination syndrome. The Rome diagnostic criteria are set forth by Rome Foundation, a not for profit 501(c)(3) organization based in Raleigh, North Carolina, United States. History Several systematic approaches attempted to classify functional gastrointestinal disorders (FGIDs). As a result, there were several key events which ultimately led to the current Rome Classification. In 1962, Chaudhary and Truelove published their study of IBS patients in Oxford, England. This was the first attempt to classify the new field of functional gastrointestinal disorders. Much of what they reported has persisted to the present day. Subsequently, in 1978 came the "Manning Criteria" developed by Heaton and colleagues in Bristol. This characterized IBS-D (IBS with predomina ...
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Uroguanylin
Uroguanylin is a 16 amino acid peptide that is secreted by enterochromaffin cells in the duodenum and proximal small intestine. Guanylin acts as an agonist of the guanylyl cyclase receptor guanylate cyclase 2C (GC-C), and regulates electrolyte and water transport in intestinal and renal epithelia. By agonizing this guanylyl cyclase receptor, uroguanylin and guanylin cause intestinal secretion of chloride and bicarbonate to dramatically increase; this process is helped by the second messenger cGMP. Its sequence is H-Asn-Asp-Asp-Cys(1)-Glu-Leu-Cys(2)-Val-Asn-Val-Ala-Cys(1)-Thr-Gly-Cys(2)-Leu-OH. In humans, the uroguanylin peptide is encoded by the ''GUCA2B'' gene. Uroguanylin may be involved in appetite and perceptions of 'fullness' after eating meals, as suggested by a study into mice. See also * Natriuretic peptide * Plecanatide Plecanatide, sold under the brand name Trulance, is a medication for the treatment of chronic idiopathic constipation (CIC) and irritable bowel synd ...
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