Mechanism of action
The drug belongs to synthetic antimycotics and acts at early stages of sterol synthesis in the fungal cell. Terbinafine selectively and reversibly inhibits the squalene epoxidase (squalene-2,3-epoxidase) enzyme of the cytoplasmic membrane.
As a result, the conversion of squalene into squalene epoxide (and subsequently into lanosterol) is blocked, leading to a deficiency of ergosterol—a vital component of the fungal membrane—and the intracellular accumulation of toxic squalene, causing pathogen death. An important difference from azole antifungals is that allylamines do not affect the 14-α-demethylase enzyme and do not depend directly on the cytochrome P-450 system, although they are metabolized via hepatic enzymes.
Pharmacological profile and pharmacokinetics
Upon oral administration, the bioavailability of terbinafine is about 40% due to presystemic metabolism (first-pass hepatic effect). The drug is characterized by high plasma protein binding (99%).
Due to its lipophilic properties, the active substance is actively distributed and accumulates in keratin-containing (skin, nails) and adipose tissues. The half-life ($T_{1/2}$) is approximately 300 hours, ensuring prolonged circulation and deposition of the drug in the affected areas.
Indications for use
The spectrum of clinical activity of terbinafine focuses on pathogens of superficial mycoses. The drug is one of the drugs of choice for dermatophytoses (infections of the skin and its appendages—nails and hair) caused by dermatophyte fungi (trichophytosis, microsporia, epidermophytosis).
Indications for systemic use (oral):
- Onychomycosis (fungal nail plate infections).
- Mycoses of the scalp and smooth skin.
- Pityriasis versicolor.
Topical use (1% ointment): Applied topically for fungal skin infections and epidermophytosis.
Safety profile, adverse effects, and contraindications
The drug is contraindicated in severe renal or hepatic impairment, as well as during pregnancy.
Adverse effects:
- Common: dyspeptic disorders (nausea, abdominal pain, diarrhea, loss of appetite), allergic skin reactions (rash).
- Rare but severe: hepatotoxicity (requires regular monitoring of liver enzymes during the course), hematological disorders (neutropenia), severe skin reactions (including Stevens-Johnson syndrome), and possible exacerbation of autoimmune pathologies (psoriasis, subacute cutaneous lupus erythematosus).
- Local reactions (with ointment application): skin hyperemia, burning, and pruritus at the application site.
Drug interactions:
- Cimetidine (a CYP450 inhibitor) can increase plasma terbinafine concentrations.
- Rifampin (a hepatic enzyme inducer), conversely, decreases blood levels of the drug.
Prescribing specifics and formulation
In practical pharmacology, terbinafine is available as 0.125 g and 0.25 g tablets, as well as a 1% ointment (in 15 and 30 g tubes).
Sample prescription formulation (in Latin):
- Rp.: Unguenti Terbinafini 1% - 30 g
- D. S. Apply externally to affected skin areas 1-2 times daily.
For systemic oral administration:
- Rp.: Tab. Terbinafini 0,25 N. 28
- D. S. Take 1 tablet (0.25 g) orally once daily.
Briefly: answers to topical questions
What laboratory parameters must be monitored during prolonged systemic administration of terbinafine?
During systemic administration of terbinafine, liver enzyme levels must be monitored. This laboratory monitoring is required throughout the entire course of treatment due to the risk of hepatotoxicity.
Additionally, it should be noted that the drug can cause rare but severe side effects:
- Hepatotoxicity — requires mandatory monitoring of liver enzymes.
- Hematological disorders — include the development of neutropenia.
There are no direct instructions in the sources regarding mandatory regular blood count monitoring, but monitoring liver function is strictly mandatory.
What is the metabolic pathway and elimination route of terbinafine from the body?
Terbinafine undergoes presystemic metabolism in the liver, resulting in a first-pass effect. Due to hepatic elimination, the oral bioavailability of the drug is approximately 40%.
During distribution and elimination, the drug accumulates in the following structures:
- Keratin-containing tissues — skin and nails.
- Adipose tissues — fat cells.
The elimination of terbinafine from the body is slow. The drug is characterized by prolonged circulation, and its elimination half-life is approximately 300 hours.
The allylamine TERBINAFINE strikes the enemy at an early stage: it blocks squalene epoxidase in the nails and skin!
Class and exam questions
Which microbial cell enzyme does terbinafine block?
Terbinafine selectively inhibits the enzyme squalene epoxidase, disrupting the early stage of ergosterol synthesis and leading to the accumulation of toxic squalene.
Why is terbinafine effective in the treatment of onychomycosis?
The drug exhibits high lipophilicity and the ability to accumulate in keratin-containing tissues (nails and hair), while its long half-life (approximately 300 hours) ensures a sustained therapeutic concentration at the infection site.
What is the difference between the mechanism of action of terbinafine and azole derivatives?
Allylamines (terbinafine) block ergosterol synthesis at an earlier stage by inhibiting squalene epoxidase, whereas azoles inhibit cytochrome P-450-dependent 14-$\alpha$-demethylase.
What else to study on this topic
- Comparative pharmacodynamics of allylamines (naftifine, butenafine, terbinafine)
- Effect of cytochrome P-450 inducers and inhibitors on the pharmacokinetics of antimycotics
- Biochemical consequences of squalene accumulation in the fungal cell
- Monitoring of laboratory parameters (hepatic transaminases, complete blood count with differential) during systemic therapy
- Features of pharmacotherapy for onychomycosis in patients with concomitant gastrointestinal and hepatic pathology
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