Model Answer
0 min readIntroduction
Griseofulvin is an antifungal medication primarily used in the treatment of dermatophyte infections of the skin, hair, and nails. Discovered in 1939 by Robert Christensen from *Penicillium griseofulvum*, it was one of the first systemic antifungal drugs available. Its mechanism of action differs significantly from newer antifungals, making it a unique therapeutic agent. While its use has declined with the advent of newer azole antifungals, Griseofulvin remains relevant in specific clinical scenarios, particularly in pediatric cases and certain refractory infections. Understanding its pharmacology is crucial for appropriate clinical application.
Mechanism of Action
Griseofulvin exerts its antifungal effect by disrupting fungal mitosis. Specifically:
- Microtubule Inhibition: Griseofulvin binds to tubulin, a protein essential for microtubule formation. Microtubules are vital for the formation of the mitotic spindle, which is crucial for cell division.
- Disruption of Spindle Formation: By binding to tubulin, Griseofulvin inhibits microtubule polymerization, leading to disruption of the mitotic spindle. This prevents fungal cells from dividing and replicating.
- Specificity for Fungal Cells: Griseofulvin has a higher affinity for fungal tubulin than for mammalian tubulin, explaining its selective toxicity.
- Accumulation in Keratin: Griseofulvin has a lipophilic nature and readily accumulates in keratinized tissues (skin, hair, nails). This allows it to reach the site of infection effectively.
It's important to note that Griseofulvin is a time-dependent killer, meaning its efficacy is related to the duration of exposure rather than peak concentration.
Uses
Griseofulvin is primarily indicated for the treatment of dermatophyte infections:
- Tinea Capitis (Scalp Ringworm): This is a common indication, particularly in children.
- Tinea Corporis (Body Ringworm): Effective for localized infections.
- Tinea Cruris (Jock Itch): Used for treating fungal infections in the groin area.
- Tinea Pedis (Athlete's Foot): Can be used, but often less effective than topical treatments.
- Tinea Unguium (Onychomycosis - Nail Infection): Requires prolonged treatment (6-12 months) due to slow nail growth.
Griseofulvin is generally not used for systemic fungal infections or yeast infections.
Side Effects
Griseofulvin can cause a range of side effects, varying in severity:
- Common Side Effects:
- Nausea, vomiting, abdominal discomfort
- Headache
- Erythema (skin rash)
- Less Common but Serious Side Effects:
- Hepatotoxicity: Liver enzyme elevation and, rarely, hepatitis.
- Neurotoxicity: Peripheral neuropathy, confusion, seizures (rare).
- Hematologic Effects: Leukopenia, eosinophilia, thrombocytopenia.
- Photosensitivity: Increased sensitivity to sunlight.
- Allergic Reactions: Urticaria, angioedema, anaphylaxis (rare).
Contraindications: Griseofulvin is contraindicated in patients with hepatic disease, porphyria, and pregnancy. Drug interactions are also important to consider, particularly with warfarin and oral contraceptives.
Conclusion
Griseofulvin, despite being an older antifungal agent, remains a valuable option for specific dermatophyte infections, particularly tinea capitis. Its unique mechanism of action, involving microtubule disruption and keratin accumulation, differentiates it from newer antifungals. However, its potential for side effects, including hepatotoxicity and neurotoxicity, necessitates careful patient monitoring and consideration of contraindications. While newer azoles have become more prevalent, a thorough understanding of Griseofulvin’s pharmacology is essential for comprehensive dermatological care.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.