**Core Concept**
The question is testing the student's understanding of the antifungal agents' mechanisms of action, specifically their effects on cell membrane permeability. **Cell membrane permeability** is a critical aspect of fungal cell function, and alterations in this property can lead to fungal cell death.
**Why the Correct Answer is Right**
The correct answer is a specific antifungal agent that does not act by altering cell membrane permeability. Most antifungal agents work by either altering the cell membrane permeability or interfering with the synthesis of essential components of the fungal cell wall or cell membrane. For example, polyenes like amphotericin B bind to ergosterol in the fungal cell membrane, altering its permeability, while azoles inhibit ergosterol synthesis. However, the correct answer does not rely on these mechanisms.
**Why Each Wrong Option is Incorrect**
* **Option A:** Polyenes like amphotericin B act by altering cell membrane permeability, as they bind to ergosterol and disrupt the fungal cell membrane. Therefore, this option is incorrect as it does act by altering cell membrane permeability.
* **Option B:** Azoles, such as fluconazole, inhibit ergosterol synthesis, which indirectly affects cell membrane permeability. This option is incorrect as it does indeed alter cell membrane permeability.
* **Option D:** Griseofulvin acts by inhibiting fungal microtubule function, which is a different mechanism of action. However, this option is not the correct answer, and we will discuss it later.
**Clinical Pearl / High-Yield Fact**
It is essential to recognize the different mechanisms of action of antifungal agents, as this knowledge can guide the selection of the most appropriate treatment for a specific fungal infection.
**Correct Answer:** D. Griseofulvin.
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