Echinocandins
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Echinocandins
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Anidulafungin p. 194, 198
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Echinocandins are a novel class of medications used to treat mycoses, or fungal infections.
Mycoses can be localized skin infections, or develop into systemic infections in immunodeficient patients.
Antifungals work either through fungistatic action, meaning that they inhibit fungal growth, or through fungicidal action, meaning they kill the fungi.
Now, most fungi have a protective cell wall made of different carbohydrate molecules.
Some fungal species have beta glucans which are polysaccharide polymers that are cross linked with other carbohydrate molecules to make a strong fungal cell wall.
Beta glucans are produced by an enzyme on the cell membrane called beta-1,3-D-glucan synthase.
This enzyme is not found in human cells which makes it a good target for antifungal medications.
Now, echinocandins are a type of medication that noncompetitively bind to and inhibit beta-1,3-D-glucan synthase.
This weakens the cell wall and prevents it from being repaired.
The cell wall gradually deforms more and more until it ruptures, causing the cell to die.
Echinocandins are only available via IV since they are not well absorbed through the GI tract.
Medications in this class include anidulafungin, micafungin, and caspofungin.
They are only effective against fungal species that have beta-1,3-D-glucan synthase, but it’s extremely rare for these organisms to have resistance to these medications.
Because of this, echinocandins are often used to treat fungal infections that are resistant to the more common antifungal medications like amphotericin-B and the “azole” medications like fluconazole.
Echinocandins are used to treat mucocutaneous candidiasis, which affect the skin, nails, and oral mucosa, or disseminated candidiasis, where the infection spreads to multiple organ systems through the blood, causing endocarditis, endophthalmitis, and osteomyelitis.
This is only seen in people with a compromised immune system like those with an HIV infection, or patients undergoing chemotherapy.
Echinocandins are also used to treat invasive aspergillosis.
Summary
Echinocandins are a class of antifungals, mainly used to treat infections caused by candida species and aspergillus species. They work by disrupting the formation of the fungal cell wall, leading to cell death. They inhibit eta-1,3-D-glucan synthase, an enzyme necessary for the synthesis of major fungal cell components known as Beta glucans. Echinocandins are generally well-tolerated and have a low risk of serious adverse effects.
The most common side effects are facial flushing, nausea, vomiting, and skin rash. Rare but serious side effects include anaphylaxis (a life-threatening allergic reaction) and Stevens-Johnson syndrome (a severe skin reaction).
Sources
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Echinocandins--new antifungal agents" Rev Med Chir Soc Med Nat Iasi (2014)
- "Echinocandins in antifungal pharmacotherapy" Journal of Pharmacy and Pharmacology (2017)
- "Clinical hepatotoxicity associated with antifungal agents" Expert Opinion on Drug Safety (2016)
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