This MedLibrary.org supplementary page on Echinocandin is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
Echinocandins are antifungal drugs that inhibit the synthesis of glucan in the cell wall, probably via noncompetetive inhibition of the enzyme 1,3-β glucan synthase[1][2] and are thus called penicillin of antifungals (a property shared with papulacandins, see history below).
Contents |
Uses
It is used in candidiasis and aspergillosis.[3]
They are fungicidal against yeast eg most species of Candida (but not against Cryptococcus, Trichosporon & Rhodotorula) and fungistatic against mold eg Aspergillus (but not Fusarium & Rhizopus) modest or minimally active active against dimorphic fungi eg Blastomyces and Histoplasma. These have some activity against the spores of the fungus Pneumocystis carinii.
History
The present day clinically used echinocandins are semisynthetic pneumocandins which are chemically lipo-peptide in nature, consisting of large cyclic (hexa)peptides linked to a long chain fatty acid. Discovery of echinocandins stemmed from studies on papulacandins isolated from a strain of Papularia sphaerosperma (Pers.), which were lipo-saccharide ie fatty acid derivatives of a disaccharide which also blocked the same target 1,3-β glucan synthase and had only anti-candida action (narrow spectrum). Screening of natural products of fungal fermentation in 1970's lead to the discovery to Echinocandins new group of antifungals with broad range activity against Candida species. One of the first Echinocandins of the pneumocandin type, discovered in 1974, Echynocandin B could not be used clinically due to risk of high degree of hemolysis. Screening semisynthetic analogs of the echinocandins gave rise to Cilofungin, first echinofungin analog that entered clinical trials in 1980, which was later withdrawn for a toxicity presumably due to the solvent system needed for systemic administration. The semisysnthetic pneumocandin analogs of echinocandins were later found to have the same kind of antifungal activity but low toxicity. The first approved of these newer echinocandins was Caspofungin and later Micafungin and Anidulafungin were also approved. All these preparations so far have low oral bioavailability and thus must be given intravenous only. Echinocandins have now become one of the first line treatments for Candida before the species are identified, and even as antifungal prophylaxis in hematopoietic stem cell transplant patients.
Advantages
Advantages of echinocandins:
- broad range (especially against all candida), thus can be given empirically in febrile neutropenia & stem cell transplant
- Can be used in case of azole resistant candida or use as a second line agent for refractory aspergillosis
- long half life (polyphasic elimination: alpha phase 1-2 hours + beta phase 9-11 hours + gamma phase 40-50 hours)
- low toxicity : only histamine release (3%), fever (2.9%), nausea and vomiting (2.9%), and phlebitis at the injection site (2.9%), very rarely allergy and anaphylaxis
- not an inhibitor, inducer, or substrate of the cytochrome P450 system, or P-glycoprotein, thus minimal drug interactions
- lack of interference from renal failure and hemodialysis.
- no dose adjustment is necessary based on age, gender, race
- better (or no less effective) than Amphotericin B and fluconazole against yeast infections
Disadvantages
Disadvantages of echinocandins:
- Embryotoxic[4] (category C) thus cannot be used in pregnancy
- Needs dose adjustment in liver disease
Interference
Capsofungin has some interference with cyclosporin metabolism and micafungin has some interference with sirolimus (rapamycin), but anidulafungin needs no dose adjustments when given with cyclosporin, tacrolimus or voriconazole [5].
Examples
List of echinocandins:
- pneumocandins (cyclic hexa-peptides linked to a long chain fatty acid):
- Echinocandin B not clinically used for risk of hemolysis
- Cilofungin (withdrawn from trials due to solvent toxicity)
- Caspofungin (Cancidas®)
- Micafungin (FK463)
- Anidulafungin (VER-002, V-echinocandin, LY303366)
See also
- papulacandins (fatty acid derivatives of a disaccharide)
References
- ^ Morris MI, Villmann M (September 2006). "Echinocandins in the management of invasive fungal infections, part 1". Am J Health Syst Pharm 63 (18): 1693–703. doi:. PMID 16960253.
- ^ Morris MI, Villmann M (October 2006). "Echinocandins in the management of invasive fungal infections, Part 2". Am J Health Syst Pharm 63 (19): 1813–20. doi:. PMID 16990627.
- ^ Wagner C, Graninger W, Presterl E, Joukhadar C (2006). "The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications". Pharmacology 78 (4): 161–77. doi:. PMID 17047411.
- ^ "Pharmacotherapy Update - New Antifungal Agents: Additions to the Existing Armamentarium (Part 1)".
- ^ Harroison's Principle of Internal Medicine
 |
This antimicrobial-related article is a stub. You can help Wikipedia by expanding it. |
|
|||||||||||||||||||||||||||
Wikipedia content modification information:
- This page was last modified on 6 October 2008, at 05:21.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Echinocandin".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.