Amphotericin B (Fungilin, Fungizone, Abelcet, AmBisome, Fungisome, Amphocil, Amphotec) is a polyene antifungal drug, often used intravenously for systemic fungal infections. It was originally extracted from Streptomyces nodosus, a filamentous bacterium, in 1955 at the Squibb Institute for Medical Research from cultures of an undescribed streptomycete isolated from the soil collected in the Orinoco River region of Venezuela. Its name originates from the chemical's amphoteric properties. Two amphotericins, Amphotericin A and Amphotericin B are known, but only B is used clinically because it is significantly more active in vivo. Currently the drug is available as plain Amphotericin B, as cholesteryl sulfate complex, as lipid complex, and as liposomal formulation. The latter formulations have been developed to improve tolerability for the patient but may show considerably different pharmacokinetic characteristics compared to plain Amphotericin B. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Polyenes are poly-unsaturated organic compounds that contain one or more sequences of alternating double and single carbon-carbon bonds. ... Something antifungal kills or inhibits the growth of fungus. ... This article does not cite any references or sources. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Divisions Chytridiomycota Zygomycota Ascomycota Basidiomycota The Fungi (singular: fungus) are a large group of organisms ranked as a kingdom within the Domain Eukaryota. ... An infection is the detrimental colonization of a host organism by a foreign species. ... Streptomyces is a genus of Actinobacteria. ... Hyphae of Penicillium A hypha (plural hyphae) is a long, branching filamentous cell of a fungus, and also of unrelated Actinobacteria. ... Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ... This page is about the Orinoco River, for the Aphra Behn novel see Oroonoko With a length of 2140 km, the Orinoco is one of the largest rivers of South America. ... In chemistry, an amphoteric substance is one that can react with either an acid or base (more generally, the word describes something made of, or acting like, two components). ... In vivo (Latin for (with)in the living). ...

Uses

Oral preparations of amphotericin B are used to treat oral thrush; these are virtually nontoxic. The main i.v. use is in systemic fungal infections (e.g. in immunocompromised patients), and in visceral leishmaniasis. Aspergillosis, Naegleria fowleri primary amoebic meningoencephalitis, cryptococcus infections (e.g. meningitis) and candidiasis are treated with amphotericin B. It is also used empirically in febrile immunocompromised patients who do not respond to broad-spectrum antibiotics. Candidiasis, commonly called yeast infection or thrush, is a fungal infection of any of the Candida species, of which Candida albicans is the most common. ... toes infection brown with white markings ... Immunosuppression is the medical suppression of the immune system. ... Visceral leishmaniasis (VL), also known as kala-azar and black fever, is the most severe form of leishmaniasis, a disease caused by parasites of the Leishmania genus. ... Binomial name Carter (1970) Naegleria fowleri (pronounced //) is a free living amoeba typically found in warm fresh water, from 25–35 degrees Celsius (77–95 degrees Fahrenheit) in an amoeboid or temporary flagellate stage. ... Binomial name Naegleria fowleri Carter (1970) Naegleria fowleri (pronounced nuh-GLEER-e-uh) is a free living amoeba typically found in warm fresh water, from 25-35 degrees Celsius in a flagellated stage. ... Cryptococcus is a genus of fungus. ... Meningitis is the inflammation of the protective membranes covering the central nervous system, known collectively as the meninges. ... An analogue medical thermometer showing the temperature of 38. ... A broad-spectrum antibiotic is so called due to its activity against a wide range of infectious agents. ...

Mechanism of action

As with other polyene antifungals, amphotericin B associates with ergosterol, a membrane chemical of fungi, forming a pore that leads to K⁺ leakage and fungal cell death. Recently, however, researchers found evidence that pore formation is not necessarily linked to cell death (i.e. Angewandte Chemie Int. Ed. Engl. 2004). The actual mechanism of action may be more complex and multi-faceted. Ergosterol (ergosta-5,7,22-trien-3β-ol), a sterol, is the biological precursor to Vitamin D2. ... General Name, symbol, number potassium, K, 19 Chemical series alkali metals Group, period, block 1, 4, s Appearance silvery white Standard atomic weight 39. ...

Amphotericin B is believed to interact with membrane sterols (ergosterol) to produce an aggregate that forms a transmembrane channel. Intermolecular hydrogen bonding interactions among hydroxyl, carboxyl and amino groups stabilize the channel in its open form, destroying activity and allowing the cytoplasmic contents to leak out. Ergosterol (ergosta-5,7,22-trien-3β-ol), a sterol, is the biological precursor to Vitamin D2. ...

Side effects

Very often a serious acute reaction after the infusion (1 to 3 hours later) is noted consisting of fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea, and tachypnea. This reaction sometimes subsides with later applications of the drug and may in part be due to histamine liberation. An increase in prostaglandin-synthesis may also play a role. Often the most difficult decision has to be made, whether the fever is disease- or drug-related. In order to decrease the likelihood and severity of the symptoms, initial doses should be low and increased slowly. The liposomal preparation obviously has a lower incidence of the syndrome. Acetaminophen, pethidine, diphenhydramine and/or hydrocortisone have all been used to treat or prevent the syndrome, but the prophylactic use of these drugs should be limited. An analogue medical thermometer showing the temperature of 38. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... Anorexia (deriving from the Greek α(ν)- (a(n)-, a prefix that denotes absence) + όρεξη (orexe) = appetite) is the decreased sensation of appetite. ... For other uses, see Nausea (disambiguation). ... Emesis redirects here. ... A headache (cephalgia in medical terminology) is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ... Dyspnea (R06. ... Tachypnea is a medical term for breathing which is more rapid than normal. ... E1 - Alprostadil I2 - Prostacyclin A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. ...

Nephrotoxicity (kidney damage) is a major issue and can be severe and/or irreversible. It is much milder when amphotericin B is delivered in liposomes (AmBisome). Electrolyte imbalances (e.g. hypokalemia and hypocalcemia) may also occur. Nephrotoxicity is a poisonous effect of some substances, both toxins and medication, on the kidney. ... A liposome is a spherical vesicle with a membrane composed of a phospholipid and cholesterol bilayer. ... Hypokalemia is a potentially fatal condition in which the body fails to retain sufficient potassium to maintain health. ... In medicine, hypocalcaemia is the presence of less than a total calcium of 2. ...

Increased liver enzymes and hepatotoxicity up to acute liver failure, several forms of anemia and other blood dyscrasias (leukopenia, thrombopenia), serious cardiac arrhythmia (including ventricular fibrillation), and cardiac failure have also been reported frequently. Skin reactions, including serious forms, are also possible. Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. ... Leukopenia or leukocytopenia refers to a decrease in the number of circulating white blood cells (leukocytes) in the blood. ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... A cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. ... Ventricular fibrillation (V-fib or VF) is a cardiac condition which consists of a lack of coordination of the contraction of the muscle tissue of the large chambers of the heart that eventually leads to the heart stopping altogether. ...

Interactions

• Flucytosine : Toxicity of Flucytosine increased and vice versa
• Diuretics or Cisplatin : Increased renal toxicity and incrised risk of hypokalemia
• Corticosterioids : Increased risk of hypokalemia
• Cytostatic drugs : Increased risk of kidney damage, hypotension and bronchospasms.
• Other nephrotoxic drugs : Increased risk of serious renal damage. Monitor patients closely.
• Foscarnet, Ganciclovir, Tenofovir, Adefovir : Risk of hematological and renal side-effects of Amphotericin B increased.
• Transfusion of Leukocytes : Risk of pulmonal (lung) damage. Space intervals between the application of Amphotericin B and the transfusion and monitor pulmonary function.

Flucytosine, or 5-fluorocytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug. ...

Liposomal and lipid complex preparations

From studies it appears that liposomal amphotericin B preparations exhibit fewer side-effects while having similar efficacy. Various preparations have recently been introduced. All of these are more expensive than plain Amphotericin B. A liposome is a spherical vesicle with a membrane composed of a phospholipid and cholesterol bilayer. ...

AmBisome is a liposomal formulation of amphotericin B for injection, developed by NeXstar Pharmaceuticals (acquired by Gilead Sciences in 1999). It is marketed by Gilead in Europe and licensed to Astellas Pharma (formerly Fujisawa Pharmaceuticals) for marketing in the USA, and Sumitomo Pharmaceuticals in Japan. An injection is a method of putting liquid into the body with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body. ... Gilead Sciences NASDAQ: GILD is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases, principally HIV, hepatitis B and influenza. ... Astellas Pharma Inc. ...

Fungisome is a liposomal complex of Amphotericin B and being the latest and cheapest addition to the lipid formulations of Amphotericin B has many advantages. It is marketed by Lifecare Innovations of India. Other formulations include Amphotec (Intermune) and Abelcet (Enzon Pharmaceuticals).

Abelcet is not a liposomal preparation but rather a lipid complex preparation.

External links

• Fungisome web site run by Lifecare Innovations
• AmBisome web site run by Astella Pharma
• (2005) "Special issue". Journal of Postgraduate Medicine 51 (Suppl).