Griseofulvin

Mechanism of action and spectrum of activity

The antifungal antibiotic griseofulvin has a unique mechanism of action that fundamentally distinguishes it from other classes of antifungals. Chemically, it is not a polyene. While most modern drugs disrupt the fungal cell membrane, this antibiotic targets reproductive processes.

Upon entering the pathogen cell, the drug specifically inhibits mitosis. Its primary site of action is the mitotic spindle, the structure of which it irreversibly disrupts. Important for differential diagnosis: the drug does not block ergosterol synthesis and does not form ion channels in the membrane.

The spectrum of antifungal activity of the drug is extremely narrow. It works exclusively against pathogens of dermatophytosis — fungi that infect the stratum corneum of the skin, hair, and nails. Prescribing it for candidiasis or severe systemic mycoses is completely ineffective.

Drug interactions

A key pharmacological feature of the drug is its ability to act as an inducer of hepatic microsomal enzymes, primarily the cytochrome P-450 system. By triggering enhanced synthesis of these enzymes, the antibiotic significantly accelerates the metabolism of other drugs the patient is taking concurrently.

The consequence of this accelerated degradation is a sharp weakening of the clinical effect of concomitant therapy. In clinical practice, interactions with the following groups are most critical:

• Indirect anticoagulants: their accelerated elimination increases the risk of thrombosis.
• Glucocorticoids: the anti-inflammatory and immunosuppressive effects of the hormones decrease.
• Estrogen-containing oral contraceptives: accelerated breakdown of estrogens can lead to unintended pregnancy.

Interaction with ethanol deserves special attention. Combining it with alcoholic beverages is strictly contraindicated, as the antibiotic manifoldly enhances the toxic effects of alcohol on the body.

Side effects and risks

Despite its narrow spectrum of action, the drug has a systemic effect on the patient's body, manifested in a wide range of side effects. One of the strict special warnings is the ability of the antibiotic to provoke and exacerbate attacks of intermittent porphyria.

Adverse reactions are classified by organ system:

• Central nervous system and sensory organs: therapy is often accompanied by headache and dizziness. In severe cases, confusion and peripheral neuritis are observed. Ocular manifestations typically include impaired close-up focusing (near-vision impairment).
• Gastrointestinal tract: mucous membranes react with dry mouth and stomatitis. Dyspeptic disorders frequently occur: heartburn, nausea, vomiting, and diarrhea.
• Blood system: toxic effects on the bone marrow manifest as changes in the hemogram — leukopenia, neutropenia, and compensatory monocytosis develop.
• Hepatobiliary and urinary systems: the liver responds with elevated hepatic transaminases and jaundice. Renal filtration is impaired, leading to albuminuria.
• Immune system and skin: allergic reactions range from angioedema and serum sickness syndrome to life-threatening dermatoses — exfoliative dermatitis and toxic epidermal necrolysis.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Comparative characteristics of griseofulvin and polyene antibiotics.
• The mechanism of cytochrome P-450 induction and the clinical significance of this process.
• Pathogenesis of toxic epidermal necrolysis during antifungal therapy.
• The effect of antifungal drugs on the course of intermittent porphyria.
• Differential diagnosis of dermatophytosis and systemic mycoses when choosing therapy.

Other topics in the section "Antifungal agents"

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