AssessmentsMiscellaneous antifungal medications
Miscellaneous antifungal medications
Content Reviewers:Yifan Xiao, MD
Contributors:Tanner Marshall, MS, Evan Debevec-McKenney, Maria Emfietzoglou, MD, Ursula Florjanczyk, MScBMC
Antifungal agents are a class of medications used to treat mycoses, or fungal infections.
Mycoses can be superficial, meaning they are localized on the skin, 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, antifungals include the azole family and a novel class of medications, echinocandins; but there are also many other antifungals with similar or different mechanisms that we’ll talk about in this video.
Okay, most fungal cells have a tough outer cell wall and an inner cell membrane.
The cell membrane is mostly made of phospholipids with some sterol or modified steroid molecules mixed in.
Now, the precursor to both molecules is lanosterol.
The precursor of lanosterol is squalene.
The conversion of squalene to lanosterol is catalyzed by an enzyme called squalene epoxidase.
Fungi have a cytochrome p450 enzyme called fourteen-alpha-demethylase in their mitochondria and endoplasmic reticulums, which converts lanosterol to ergosterol.
Without ergosterol, the structure of the cell membrane will be disrupted.
This will cause membrane-bound proteins, like ion channels, to stop working properly.
The membrane also becomes fragile, which eventually leads to inhibition of fungal growth.
They bind to ergosterol, and the hydrophilic core causes the formation of artificial pores in the cell membrane, thereby creating a leaky membrane.
This causes significant changes in ion balance including the loss of intracellular potassium.
Depending on their concentration, polyenes are either fungistatic or fungicidal.
Now, amphotericin B is one of the most important medications for the treatment of systemic mycoses. It’s used to fight systemic infections caused by Aspergillus, Blastomyces, Candida albicans, Cryptococcus, Histoplasma, and Mucor, either alone or in combination with other drugs.
Amphotericin B is also used in the treatment of visceral Leishmaniasis, caused by protozoan parasites of the genus Leishmania, that presents with fever, weight loss, fatigue, anemia, and substantial swelling of the liver and spleen.
In fungal meningitis intrathecal administration, meaning injection into the spinal canal, or into the subarachnoid space, has been used, since the drug is widely distributed to all tissues except the central nervous system, or CNS, when administered intravenously.
Amphotericin is mainly eliminated via hepatic metabolism, while a small fraction is excreted through the kidneys.
The most serious side effect is renal toxicity which is dose dependent and can be decreased with hydration.
Anemia may also occur due to reduction of erythropoietin production from the kidneys.
The electrolyte imbalance can cause arrythmias.
It’s used either topically for superficial infections or orally to fight gastrointestinal fungi in patients with impaired defense mechanisms.
Side effects for the oral form include gastrointestinal disturbances like nausea, abdominal pain, vomiting, and diarrhea.
Both the oral and the topical form can cause hypersensitivity reactions such as Stevens-Johnson syndrome, which is a dangerous immune-mediated condition that affects the skin and mucous membranes such as the mouth and genitals, and also rashes, itching, and burning.
There are a few different types of antifungal medications, but they all work in similar ways. Most of them work by disrupting the formation of the fungal cell wall, which eventually kills the fungus. Some common antifungal medications include azoles (such as fluconazole and itraconazole), polyenes (such as amphotericin B and nystatin), and echinocandins (such as caspofungin and anidulafungin).
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