Lect 5
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Amphotericin B is a naturally occurring, polyene macrolide antibiotic produced by Streptomyces nodosus that is the drug of choice for treating life-threatening, systemic mycoses despite its toxic potential. It works by binding to ergosterol in the plasma membranes of fungi, forming pores that disrupt membrane function and cause cell death. Amphotericin B has a broad antifungal spectrum against many Candida, Histoplasma, Cryptococcus, Coccidioides, and Aspergillus species. While infrequent, resistance can develop through decreased ergosterol content. Its major adverse effects include fever, chills, renal impairment, hypotension, anemia, and neurological
![Antifungal Drugs:
Infectiousdiseasescausedbyfungi are calledmycoses,andtheyare oftenchronicinnature.1
Many
commonmycoticinfectionsare superficial andonlyinvolvethe skin(cutaneousmycoses),butfungi may
alsopenetrate the skin,causingsubcutaneousinfections. Unlike bacteria,fungi are eukaryotic.They
have rigidcell wallscomposedlargelyof chitin但apolymerof N-acetylglucosamine但ratherthan
peptidoglycan(acharacteristiccomponentof mostbacterial cell walls).
CLASSIFICATION:
DRUGS FOR SUBCUTANEOUS AND SYSTEMIC MYCOSIS:
1) Amphotericin-B
2) Ketoconazole
3) Itraconazole
DRUGS FOR CUTANEOUS MYCOSIS:
1) Butoconazole
2) Clotrimazole
3) Nystatin
Amphotericin B:
Amphotericin [am-foe-TER-i-sin] Bisa naturallyoccurring,polyene macrolide antibioticproducedby
Streptomycesnodosus.Inspite of itstoxicpotential, amphotericinBisthe drugof choice forthe
treatmentof life-threatening,systemicmycoses.
Mechanismof action: Several amphotericin B molecules bind to ergosterol in the
plasma membranes of sensitive fungal cells. There, they form pores (channels) that
require hydrophobic interactions between the lipophilic segment of the polyene antibiotic
and the sterol (Figure 35.2). The pores disrupt membrane function, allowing electrolytes
(particularly potassium) and small molecules to leak from the cell, resulting in cell death.
[Note: Because the polyene antibiotics bind preferentially to ergosterol rather than to
cholesterol但the sterol found in mammalian membranes但a relative (but not absolute)
specificity is conferred.]
Antifungal spectrum: Amphotericin B is either fungicidal or fungistatic, depending
on the organism and the concentration of the drug. It is effective against a wide range of
fungi, including Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans,
Coccidioides immitis, Blastomyces dermatitidis, and many strains of aspergillus. [Note:
Amphotericin B is also used in the treatment of the protozoal infection, leishmaniasis.]
Resistance:Fungal resistance, although infrequent, is associated with decreased
ergosterol content of the fungal membrane.](https://image.slidesharecdn.com/lect-5-151121061855-lva1-app6892/85/Lect-5-1-320.jpg)
Lect 5
- 1. Antifungal Drugs: Infectiousdiseasescausedbyfungi are calledmycoses,andtheyare oftenchronicinnature.1 Many commonmycoticinfectionsare superficial andonlyinvolvethe skin(cutaneousmycoses),butfungi may alsopenetrate the skin,causingsubcutaneousinfections. Unlike bacteria,fungi are eukaryotic.They have rigidcell wallscomposedlargelyof chitin但apolymerof N-acetylglucosamine但ratherthan peptidoglycan(acharacteristiccomponentof mostbacterial cell walls). CLASSIFICATION: DRUGS FOR SUBCUTANEOUS AND SYSTEMIC MYCOSIS: 1) Amphotericin-B 2) Ketoconazole 3) Itraconazole DRUGS FOR CUTANEOUS MYCOSIS: 1) Butoconazole 2) Clotrimazole 3) Nystatin Amphotericin B: Amphotericin [am-foe-TER-i-sin] Bisa naturallyoccurring,polyene macrolide antibioticproducedby Streptomycesnodosus.Inspite of itstoxicpotential, amphotericinBisthe drugof choice forthe treatmentof life-threatening,systemicmycoses. Mechanismof action: Several amphotericin B molecules bind to ergosterol in the plasma membranes of sensitive fungal cells. There, they form pores (channels) that require hydrophobic interactions between the lipophilic segment of the polyene antibiotic and the sterol (Figure 35.2). The pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death. [Note: Because the polyene antibiotics bind preferentially to ergosterol rather than to cholesterol但the sterol found in mammalian membranes但a relative (but not absolute) specificity is conferred.] Antifungal spectrum: Amphotericin B is either fungicidal or fungistatic, depending on the organism and the concentration of the drug. It is effective against a wide range of fungi, including Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, and many strains of aspergillus. [Note: Amphotericin B is also used in the treatment of the protozoal infection, leishmaniasis.] Resistance:Fungal resistance, although infrequent, is associated with decreased ergosterol content of the fungal membrane.
- 2. Adverse effects: AmphotericinBhasa low therapeuticindex, Feverandchills, Renal impairment:Hypotension, Anemia, Neurologiceffects, Thrombophlebitis