A 36- year-old woman presents to the clinic with a fever, malaise, and headache for two weeks. She has been sexually active with her partner for one year. Her past medical history includes untreated HIV. The patient drinks 4-5 beers daily and uses both cocaine and marijuana. Her temperature is 38.3°C (100.9°F), pulse is 99/min, respirations are 23/min, blood pressure is 125/85 mmHg, and SpO2 of 96%. An LP and India ink stain reveal evidence of cryptococcal meningitis, and the patient is initiated on appropriate antifungal therapy. One week later, her laboratory investigations reveal the findings below. Which of the following is the pharmacological agent responsible for this patient’s condition? Laboratory value Result Complete blood count Hemoglobin 9 g/dL Leukocyte count 4,100 /mm3 Platelet count 90,000/mm3

Miscellaneous antifungal medications

USMLE® Step 2 ReviewMultisystem processes and disordersBack to the Basic SciencesPharmacologyAntibiotic, antifungal, antiparasitic, and antiviral medications

Video summary

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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Content Reviewers

Yifan Xiao, MD

Contributors

Ursula Florjanczyk, MScBMC,Maria Emfietzoglou, MD,Evan Debevec-McKenney,Tanner Marshall, MS

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.

Humans have cholesterol, while fungi have ergosterol. Both sterol molecules help keep the cell membrane stable at a wide range of temperatures.

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.

Okay, let’s start with polyenes, which are naturally-derived antifungal antibiotics that alter cell membrane permeability.

They include amphotericin, also called amphotericin B, and nystatin.

Polyenes have both hydrophilic, meaning they love water, and lipophilic, meaning they love fats, characteristics.

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.

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