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Nystatin

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Subject: Rachel Fuller Brown, Miconazole, Polyene antimycotic, Amphotericin B, WikiProject Outlines/Drafts/Outline of tinea
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Nystatin

Nystatin
Systematic (IUPAC) name
(1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E, 25E,27E,29E,31E,33R,35S,36R,37S)-33-[(3-amino-3,

6-dideoxy-β-L-mannopyranosyl)oxy]-1, 3,4,7,9,11,17,37-octahydroxy-15, 16,18-trimethyl-13-oxo-14, 39-dioxabicyclo[33.3.1]nonatriaconta-19,

21,25,27,29,31-hexaene-36-carboxylic acid
Clinical data
Trade names generics only
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • A vaginal, C oral troche
Legal status
  • (Prescription only)
Routes of
administration
topical, Vaginal,and oral (but not absorbed orally)
Pharmacokinetic data
Bioavailability 0% on oral ingestion
Metabolism None (not extensively absorbed)
Biological half-life Dependent upon GI transit time
Excretion Fecal (100%)
Identifiers
CAS Registry Number  Y
ATC code A07 D01 G01
PubChem CID:
DrugBank  Y
ChemSpider  N
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  N
NIAID ChemDB
Chemical data
Formula C47H75NO17
Molecular mass 926.09
 N   

Nystatin (originally named Fungicidin) is a health system.[2]

Contents

  • Uses 1
    • Other uses 1.1
  • Adverse effects 2
  • Mechanism of action 3
  • Biosynthesis 4
  • History 5
  • Formulations 6
  • Brand names 7
  • References 8

Uses

Cutaneous, vaginal, mucosal, and esophageal Candida infections usually respond well to treatment with nystatin. It is available in many forms. Oral nystatin is often used as a preventive treatment in people who are at risk for fungal infections, such as AIDS patients with a low CD4+ count and patients receiving chemotherapy. It has been investigated for use in patients after liver transplantation, but fluconazole was found to be much more effective for preventing colonization, invasive infection, and death.[3]

It is also used prophylactically in very low birth-weight (<1500 g) infants to prevent invasive fungal infections, although fluconazole is the preferred agent. It has been found to reduce the incidence of invasive fungal infections and also reduce deaths when used in these babies. Current clinical practice guidelines state that the use of these agents should be restricted to extremely low birth-weight infants (<1000 g) in neonatal intensive care units with high baselines of fungal infection.[4]

Liposomal nystatin is not commercially available, but investigational use has shown greater in vitro activity than colloidal formulations of amphotericin B, and demonstrated effectiveness against some amphotericin B-resistant forms of fungi.[1] It offers an intriguing possibility for difficult-to-treat systemic infections, such as invasive aspergillosis, or infections that demonstrate resistance to amphotericin B. Additionally, liposomal nystatin appears to cause fewer cases of and less severe nephrotoxicity than observed with amphotericin B.[1]

Cryptococcus is also sensitive to nystatin. In the UK, its license for treating neonatal oral thrush is restricted to those over the age of one month (miconazole is an appropriate alternative for younger babies).

It is prescribed in 'units', with doses varying from 100,000 (for oral infections) to 1 million (for intestinal ones). As it is not absorbed from the gut, it is safe for oral use and does not have problems of drug interactions. Although on occasional, serum levels of the drug can be identified from oral, vaginal, or cutaneous administration and lead to toxicity.

Other uses

It is also used in cellular biology as an inhibitor of the lipid raft-caveolae endocytosis pathway on mammalian cells, at concentrations around 3 µg/ml.

Penicillium-infected tangerine: The spot absent of growth had nystatin applied to it before the fungus covered the fruit.

In certain cases, nystatin has been used to prevent the spread of mold on objects such as works of art. For example, it was applied to wood panel paintings damaged as a result of the Arno River Flood of 1966 in Florence, Italy.

Nystatin is also used as a tool by scientists performing "perforated" patch-clamp electrophysiologic recordings of cells. When loaded in the recording pipette, it allows for measurement of electrical currents without washing out the intracellular contents, because it forms pores in the cell membrane that are permeable to only monovalent ions.[5]

Adverse effects

The oral suspension form produces a number of adverse effects including but not limited to:[6]

  1. Diarrhea
  2. Abdominal pain
  3. Rarely, tachycardia, bronchospasm, facial swelling, muscle aches

Both the oral suspension and the topical form can cause:

  1. Hypersensitivity reactions, including Stevens-Johnson syndrome in some cases [7]
  2. Rash, itching, burning and acute generalized exanthematous pustulosis[8]

Mechanism of action

Like amphotericin B and natamycin, nystatin binds to ergosterol, a major component of the fungal cell membrane. When present in sufficient concentrations, it forms pores in the membrane that lead to K+ leakage, acidification, and death of the fungus.[9] Ergosterol is unique to fungi, so the drug does not have such catastrophic effects on animals or plants. However, many of the systemic/toxic effects of nystatin are attributable to its effect on human cells via binding to mammalian sterols, namely cholesterol. This is the effect that accounts for the nephrotoxicity observed when high serum levels of nystatin are achieved.

Biosynthesis

Nystatin A1 (or referred to as nystatin) is biosynthesized by a bacterial strain, Streptomyces noursei.[10] The structure of this active compound is characterized as a polyene macrolide with a deoxysugar D-mycosamine, an amino glycoside.[10] The genomic sequence of nystatin reveals the presence of the polyketide loading module (nysA) six polyketide synthases modules (nysB, nysC, nysI, nysJ, and nysK), two thioesterase (nysK and nysE).[10] Thus, it is evident that the biosynthesis of the macrolide functionality follows the polyketide synthase I pathway.[11]

Loading to 5
Modules 6-12
Modules 13 -18

Following, the biosynthesis of the macrolide, the compound undergoes post-synthetic modifications, which are aided by the following enzymes: GDP-mannose dehydratase (nysIII), P450 monooxygenase (nysL and nysN), aminotransferase (nysDII), and glycosyltransferase (nysDI).[10] The biosynthetic pathway is thought to proceed as shown to yield nystatin.

Completed molecule

History

Elizabeth Lee Hazen (left) and Rachel Fuller Brown in 1955.

Like many other antifungals and antibiotics, nystatin is of

  1. ^ a b c Dismukes, WE; et al. Clinical Mycology. Oxford University Press. pp. 50–53. 
  2. ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  3. ^ Gøtzsche PC, Johansen HK (2014). "Nystatin prophylaxis and treatment in severely immunodepressed patients". Cochrane Database Syst Rev 9: CD002033.  
  4. ^ Pappas, PG; Kauffman CA; Andes D; et al. (2009). "Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.". Clin Infect Dis 48 (5): 503–35.  
  5. ^ Akaike N, Harata N (1994). "Nystatin perforated patch recording and its applications to analyses of intracellular mechanisms". Jpn. J. Physiol. 44 (5): 433–73.  
  6. ^ "Micromedex Detailed Drug Information". Retrieved Apr 1, 2014. 
  7. ^ "FDA approved package insert" (PDF). 
  8. ^ Rosenberger A, Tebbe B, Treudler R, Orfanos CE (1998). "[Acute generalized exanthematous pustulosis, induced by nystatin]". Hautarzt (in German) 49 (6): 492–5.  
  9. ^ Hammond, S.M. (1977). "Biological activity of polyene antibiotics.". Progress in medicinal chemistry 14 (105-179): 105–79.  
  10. ^ a b c d Fjaervik E, Zotchev SB (2005). "Biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei". Appl. Microbiol. Biotechnol. 67 (4): 436–443.  
  11. ^ Dewick, Paul M. (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). UK: John Wiley & Sons Ltd.  
  12. ^ Ana Espinel-Ingroff, Medical mycology in the United States: a historical analysis (1894-1996), Springer, 2003, p. 62.

References

Brand names

  • An oral suspension form is used for the prophylaxis or treatment of oropharyngeal thrush, a superficial candidal infection of the mouth and pharynx.
  • A tablet form is preferred for candidal infections in the intestines.
  • Nystatin is available as a topical cream and can be used for superficial candidal infections of the skin.
  • Additionally, a liposomal formulation of nystatin was investigated in the 1980s and into the early 21st century. The liposomal form was intended to resolve problems arising from the poor solubility of the parent molecule and the associated systemic toxicity of the free drug.

Formulations

) in 1954. Wadsworth Center State Health Department Laboratory (now known as the New York Hazen and Brown named nystatin after the [12]

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