General principles for prescribing second-line drugs
Second-line medications have limited use due to high toxicity to the human body. They are prescribed strictly in combination with other antituberculosis drugs, such as isoniazid or streptomycin.
This approach serves two main purposes:
- Increasing the overall therapeutic efficacy of treatment.
- Reducing the risk of mycobacterial resistance (drug resistance) to therapy.
Second-line antibiotics
This group includes natural and synthetic antibiotics with various mechanisms of action against the pathogen:
- Cycloserine — a broad-spectrum synthetic antibiotic. It exerts a bactericidal effect by disrupting cell wall synthesis. It penetrates tissue barriers well, but causes neurotoxicity (headaches, psychosis), which is managed with vitamin B6.
- Viomycin — an antibiotic of animal origin with a bacteriostatic effect on M. tuberculosis. Administered intramuscularly, it has a pronounced ototoxic effect, which is why it must not be combined with aminoglycosides.
- Capreomycin — a natural peptide antibiotic containing a PAS residue. It is prescribed for infections caused by resistant strains, but can cause nephrotoxicity and deafness.
Synthetic antituberculosis drugs
Among second-line synthetic compounds, several key pharmacological agents stand out:
- Ethionamide — a structural analogue of isoniazid. It disrupts mycolic acid synthesis and can penetrate encapsulated caseous lesions. Common adverse reactions include dyspepsia and hepatotoxicity.
- Pyrazinamide — acts as a prodrug, being converted into pyrazinoic acid by the enzyme pyrazinase. A characteristic adverse effect is hyperuricemia, leading to joint pain.
- PAS (para-aminosalicylic acid) — used in the form of salts, it acts tuberculostatically via competitive antagonism with PABA. It is effective only during the active replication phase of mycobacteria and strongly irritates the gastrointestinal mucosa.
- Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) and thioacetazone also complement the arsenal of combination therapy for tuberculosis.
Briefly: answers to topical questions
Which antibiotics belong to second-line antituberculosis drugs?
Second-line (reserve) antituberculosis antibiotics include drugs from various chemical groups, including aminoglycosides and peptide antibiotics.
- Viomycin (florimycin sulfate) — an antibiotic of animal origin.
- Capreomycin (Capreomycin) — a natural peptide antibiotic.
- Cycloserine — a broad-spectrum antibiotic.
- Kanamycin — belongs to the aminoglycoside group.
- Amikacin — belongs to the aminoglycoside group.
Which synthetic agents belong to second-line antituberculosis drugs?
Second-line (reserve) synthetic antituberculosis agents include drugs from several pharmacological groups.
- Fluoroquinolones — levofloxacin, moxifloxacin, ciprofloxacin, gatifloxacin.
- Isonicotinic acid thioamide derivatives — ethionamide, prothionamide.
- Para-aminosalicylic acid derivatives — aminosalicylic acid (PAS).
What adverse effects are characteristic of pyrazinamide?
Pyrazinamide is characterized by adverse effects affecting the gastrointestinal tract, liver, and metabolism.
- Dyspepsia.
- Hyperuricemia — retention of uric acid, which clinically manifests as arthralgia (joint pain) and myalgia.
- Hepatotoxicity.
Which fluoroquinolones are used in combination therapy for tuberculosis?
Synthetic antibacterial agents from the fluoroquinolone group are used as reserve (second-line) drugs in combination therapy for tuberculosis.
- Levofloxacin — a second-generation fluoroquinolone.
- Moxifloxacin — a second-generation fluoroquinolone.
- Ciprofloxacin.
- Gatifloxacin.
Second-line antibiotics hit precisely but hard: Cycloserine requires vitamin B6 for nerve protection, Viomycin and Capreomycin require monitoring hearing and kidneys, and Pyrazinamide monitors uric acid in the joints.
Class and exam questions
Why are second-line antituberculosis drugs always prescribed in combination?
Combination therapy is necessary to increase treatment efficacy and prevent the rapid development of mycobacterial drug resistance.
How to reduce neurotoxicity when using cycloserine?
To reduce central nervous system side effects, patients are prescribed pyridoxine (vitamin B6).
What are the specific features of pyrazinamide's mechanism of action?
Pyrazinamide is a prodrug: inside the bacterium, under the influence of pyrazinase, it is converted into active pyrazinoic acid, which destroys the pathogen's cell wall.
Why is PAS inactive against mycobacteria that are not in the division stage?
PAS acts as a competitive antagonist of PABA and disrupts folate synthesis, which is why its activity is manifested exclusively during the active replication phase of microorganisms.
What else to study on this topic
- Pharmacokinetics and metabolism of ethionamide in the liver
- Mechanism of hyperuricemia and arthralgia development during pyrazinamide intake
- Comparative characteristics of fluoroquinolones in phthisiology
- Competitive antagonism of PAS with PABA at the level of folate synthesis
- Features of cross-resistance during the use of isoniazid analogues
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