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Biguanidine
Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea. Synthesis Biguanide can be obtained from the reaction of dicyandiamide with ammonia, via a Pinner-type process. :\mathrm Biguanide was first synthesized by Bernhard Rathke in 1879. Biguanidine drugs A variety of derivatives of biguanide are used as pharmaceutical drugs. Antihyperglycemic agents The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic drugs used for diabetes mellitus or prediabetes treatment. Examples include: * Metformin - widely used in treatment of diabetes mellitus type 2 * Phenformin - withdrawn from the market in most countries due to toxic effects * Buformin - withdrawn from the market due to toxic effects File:Metformin.svg, Metformin, an asymmetric dimethylbiguanidine File:Buformin.svg, Buformin. ...
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International Union Of Pure And Applied Chemistry
The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is a member of the International Science Council (ISC). IUPAC is registered in Zürich, Switzerland, and the administrative office, known as the "IUPAC Secretariat", is in Research Triangle Park, North Carolina, United States. This administrative office is headed by IUPAC's executive director, currently Lynn Soby. IUPAC was established in 1919 as the successor of the International Congress of Applied Chemistry for the advancement of chemistry. Its members, the National Adhering Organizations, can be national chemistry societies, national academies of sciences, or other bodies representing chemists. There are fifty-four National Adhering Organizations and three Associate National Adhering Organizations. IUPAC's Inter-divisional Committee on ...
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Guanidine
Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experiencing renal failure. A guanidine moiety also appears in larger organic molecules, including on the side chain of arginine. Structure Guanidine can be thought of as a nitrogenous analogue of carbonic acid. That is, the C=O group in carbonic acid is replaced by a C=NH group, and each OH is replaced by a group. Isobutene can be seen as the carbon analogue in much the same way. A detailed crystallographic analysis of guanidine was elucidated 148 years after its first synthesis, despite the simplicity of the molecule. In 2013, the positions of the hydrogen atoms and their displacement parameters were accurately determined using single-crystal neutron diffraction. Production Guanidine can be obtained from natural sources, being first isolat ...
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Hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly. The most common cause of hypoglycemia is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. Risk is greater in diabetics who have eaten less than usual, recently exercised, or consumed alcohol. Other causes of hypoglycemia include severe illness, sepsis, kidney failure, liver disease, hormone deficiency, tumors such as insulinomas or non-B cell tumo ...
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Chronic Kidney Disease
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include (in chronological order) high blood pressure (often related to activation of the renin–angiotensin system system), bone disease, and anemia. Additionally CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization. Causes of chronic kidney disease include diabetes, high blood pressure, glomerulonephritis, and polycystic kidney disease. Risk factors include a family history of chronic kidney disease. Diagnosis is by blood tests to measure the estimated glomerular filtration rate (eGFR), and a urine test to measure albumin. Ultrasound or kidney biopsy may be performe ...
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Diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin with loss of the normal stretchiness of the skin and irritable behaviour. This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe. Loose but non-watery stools in babies who are exclusively breastfed, however, are normal. The most common cause is an infection of the intestines due to either a virus, bacterium, or parasite—a condition also known as gastroenteritis. These infections are often acquired from food or water that has been contaminated by feces, or directly from another person who is infected. The three types of diarrhea are: short duration watery diarrhea, short duration bloody diarrhea, and persistent diarrhea (lasting more than two weeks, w ...
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Gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen ( glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise. In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates ...
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Meglitinide
Meglitinides or glinides are a class of drugs used to treat type 2 diabetes. Drugs Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997. Other drugs in this class include nateglinide (Starlix) and mitiglinide (Glufast). Side effects Side effects include weight gain and hypoglycemia. While the potential for hypoglycemia is less than for those on sulfonylureas, it is still a serious potential side effect that can be life-threatening. Patients on this medication should know the signs and symptoms of hypoglycemia and appropriate management. Repaglinide caused an increased incidence in male rats of benign adenomas (tumors) of the thyroid and liver.Prandin (repaglinide) prescribing information
fda.gov
No such effect was seen with anot ...
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Sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas. A number of sulfonylureas are also used as herbicides, because they can interfere with plant biosynthesis of certain amino acids. Sulfonylureas are also used experimentally to inhibit interleukin 1 beta release from the NALP3 (or NLRP3) inflammasome. Drugs * First-generation drugs include acetohexamide, carbutamide, chlorpropamide, glycyclamide (tolcyclamide), metahexamide, tolazamide and tolbutamide. * Second-generation drugs include glibenclamide (glyburide), glibornuride, gliclazide, glipizide, gliquidone, glisoxepide and glyclopyramide. * Third-generation drugs include glimepiride, although it is sometimes considered a second-generation agent. Medical uses Sulfonylureas are used primarily for the treatment of d ...
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Hypoglycemic Agent
Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists (liraglutide, exenatide, and others), and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors. Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in type 1, which must be injected. Diabetes mellitus type 2 is a disease of insulin resistance by cells. Type 2 diabetes mellitus is the most common type of diabetes. Treatments include agents that (1) increase the amount of insulin secreted by the pancreas, (2) increase the sensitivity of target organs to insulin, (3) decrease the rate at which glucose is absorbed from the gastrointestinal tract, and (4) incre ...
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Mechanism Of Action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there. Drugs that do not bind to receptors produce their corresponding therapeutic effect by simply interacting with chemical or physical properties in the body. Common examples of drugs that work in this way are antacids and laxatives. In contrast, a mode of action (MoA) describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance. Importance Elucidating the mechanism of action of novel drugs and medications is important for several reasons: * In the case of anti-infectiv ...
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Lactic Acidosis
Lactic acidosis is a medical condition characterized by a build-up of lactate (especially -lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's oxidative metabolism. Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, Kussmaul breathing (laboured and deep), and generalised weakness. The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloro ...
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Phenformin
Phenformin is an antidiabetic drug from the biguanide class. It was marketed as DBI by Ciba-Geigy, but was withdrawn from most markets in the late 1970s due to a high risk of lactic acidosis, which was fatal in 50% of cases. Phenformin was developed in 1957 by Ungar, Freedman and Seymour Shapiro, working for the US Vitamin Corporation. Clinical trials begun in 1958 showed it to be effective, but with gastrointestinal side effects. Toxicity Phenformin sales began to decline in the US from 1973 due to negative trial studies and reports of lactic acidosis. By October 1976, the FDA Endocrinology and Metabolism Advisory Committee recommended phenformin be removed from the market. The FDA began formal proceedings in May 1977, leading to its eventual withdrawal on November 15, 1978. In 1977, 385,000 patients with early-stage diabetes were taking phenformin in the US. Ralph Nader's Health Research Group put the US government under pressure to ban the drug. Ciba-Geigy Corp resisted, claim ...
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