From the Guidelines
Griseofulvin is a fungistatic drug that inhibits nucleic acid synthesis, arrests cell division at metaphase, and impairs synthesis of the cell wall, as stated in the British Association of Dermatologists' guidelines for the management of tinea capitis 2014 1. The mechanism of action of Griseofulvin involves disrupting fungal cell division, which ultimately leads to the inhibition of fungal growth.
Key Points
- Griseofulvin is fungistatic, meaning it prevents further growth of the fungus while the body's immune system eliminates the infection.
- The medication is deposited in keratin precursor cells and incorporated into newly formed keratin, making it effective for treating dermatophyte infections of hair, skin, and nails.
- Griseofulvin concentrates in the stratum corneum, hair, and nails when administered orally, where it remains and protects against fungal invasion as these tissues grow.
- Treatment with Griseofulvin must continue until the infected keratin is replaced by new, healthy tissue, which can take several weeks to months depending on the type of infection.
- Griseofulvin is poorly absorbed and should be taken with fatty meals to enhance absorption, with common dosing for adults being 500-1000 mg daily, and children typically receiving 10-20 mg/kg/day, divided into single or multiple doses, as seen in the guidelines for the management of onychomycosis 2014 1.
Important Considerations
- Griseofulvin has several limitations, including lower efficacy, long treatment duration, and risk of greater drug interactions, making it less favorable compared to newer antifungal agents, as noted in the guidelines for the management of onychomycosis 2014 1.
- The British Association of Dermatologists' guidelines for the management of tinea capitis 2014 recommend Griseofulvin as a first-line treatment for tinea capitis in children, with a dosing regimen of 15-20 mg/kg/day for children under 50 kg, and 1 g per day for children over 50 kg 1.
From the FDA Drug Label
Microbiology: Mechanism of Action: The mechanism of griseofulvin consists of binding microtubular proteins, which are required for mitosis The mechanism of action of Griseofulvin is binding to microtubular proteins, which are necessary for mitosis, thereby preventing fungal growth. 2
- Key mechanism: Binding to microtubular proteins
- Effect on fungi: Inhibition of mitosis, preventing fungal growth
- Specificity: Active against dermatophytes, with no effect on bacteria or other genera of fungi.
From the Research
Mechanism of Action of Griseofulvin
The mechanism of action of Griseofulvin is not fully understood, but several ways are invoked:
- Inhibition of fungal cell mitosis and nuclear acid synthesis 3
- Probable interference with the function of microtubules 3
- Inhibition of nucleic acid synthesis, arresting cell division at metaphase, and impairing fungal wall synthesis 4
- Suppression of spindle microtubule dynamics, similar to more powerful antimitotic drugs 5
Effects on Microtubules
Griseofulvin has been shown to:
- Suppress the dynamic instability behavior of microtubules at low concentrations (1-20 microM) 5
- Inhibit microtubule polymerization in vitro at high concentrations (>100 microM) 5
Biological Activity
The biological activity of Griseofulvin towards fungi is manifested as:
- Nuclear and mitotic abnormalities followed by distortions in the hyphal morphology 6
- Mitotic segregation induction in fungi by Griseofulvin treatment 6
- Cytostatic action in higher eukaryotes, essentially due to a mitotic arrest at late metaphase/early anaphase 6
Cytological Effects
The cytological effects of Griseofulvin include: