Pharmacology
Summary
Griseofulvin is effective against dermatophytic infections, including tinea corporis, tinea pedis, and tinea cruris owing to its accumulation in keratin-rich tissues. It acts by binding to fungal cell microtubules, leading to a halt in mitosis. However, it can cause adverse effects, including activation of the cytochrome P-450 system of the liver.
Terbinafine is fungicidal, inhibiting ergosterol synthesis by blocking the fungal enzyme squalene epoxidase. Notably used to treat dermatophytes and onychomycosis, this oral medication deposits in keratin-containing tissues. Potential hepatotoxicity mandates careful monitoring during its use. The echinocandins are a class that includes caspofungin, micafungin, and anidulafungin. These antifungals interfere with beta-1,3-glucan synthesis, crippling the fungal cell wall. Echinocandins prove effective against candidal infections and, in some cases, invasive aspergillosis. Despite rare GI side effects, they are generally well-tolerated.
Lesson Outline
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FAQs
Griseofulvin and terbinafine are commonly used as first-line therapies for the treatment of dermatophyte infections, including tinea capitis in children. Griseofulvin, an oral antifungal agent, treats dermatophytosis by binding to fungal cell microtubules and halting mitosis. It also activates cytochrome P-450. Terbinafine, another anti-fungal agent, is used both topically and orally to treat a variety of tinea infections and onychomycosis. Terbinafine inhibits fungal squalene epoxidase, causing an accumulation of squalene that is toxic to the cells. Terbinafine can cause GI side effects and hepatotoxicity so it's important to monitor patients during treatment.
The fungal cell membrane includes ergosterol, which is different from the cholesterol found in human cells. This difference is exploited by antifungal treatments. For example, terbinafine inhibits the enzyme squalene epoxidase, which is required for ergosterol production. This results in a toxic accumulation of squalene in the fungal cell, leading to cell death.
Echinocandins, including caspofungin, micafungin, and anidulafungin, act primarily at the fungal cell wall. They inhibit the synthesis of beta-1-3-glucan, which is an essential component of fungal cell walls. This destabilises the cell wall, leading to cell death.
Echinocandins have been found to be particularly effective in treating infections caused by Candida species. They have excellent activity against a variety of Candida infections, including mucocutaneous candidiasis. For systemic Candida infections such as candidemia, they can be delivered intravenously. Echinocandins are also used to treat esophageal candidiasis and invasive aspergillosis, caused by Aspergillus fumigatus.
While terbinafine is an effective antifungal agent, it can cause some side effects. These include gastrointestinal issues such as nausea or upset stomach, and, more seriously, hepatotoxicity. As such, patients on terbinafine should be closely monitored for any signs of liver dysfunction during treatment.
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