Pathogen characteristics and causes of resistance
Tuberculosis treatment is a challenging task due to the unique biological features of the pathogen. Mycobacteria exhibit primary resistance to many conventional antibiotics.
Main factors reducing the efficacy of drug therapy:
- Slow growth: standard antimicrobial drugs target rapidly dividing cells.
- Slowed metabolism: suppression of cellular metabolic processes reduces drug activity.
- Cell wall features: the pathogen's envelope is rich in lipids, creating a reliable barrier to drug penetration.
- Intracellular localization: the mycobacterium acts as an intracellular parasite, requiring agents capable of penetrating host cells.
Principles of tuberculosis therapy
The treatment strategy is built on a strict consideration of the pathogen's properties and aims to achieve a sustained clinical effect:
- Duration of the course: therapy lasts from half a year to a year or longer to prevent potential relapses.
- Combination therapy: mandatory use of a combination of several drugs successfully overcomes mycobacterial drug resistance.
Classification of antituberculosis drugs
Depending on their source of origin, the entire arsenal of these pharmacological agents is divided into two major groups:
- Antibiotics:
- Aminoglycosides: streptomycin sulfate, kanamycin, amikacin.
- Other groups: rifampicin, viomycin (florimycin sulfate), cycloserine, capreomycin.
- Synthetic agents:
- Isonicotinic acid hydrazide derivatives: isoniazid, phthivazide.
- PAS derivatives: sodium aminosalicylate, bepask.
- Isonicotinic acid thioamide derivatives: ethionamide.
Localization of the infectious process
The disease proceeds as a severe chronic infection with diverse localization of the pathological focus:
- Respiratory tuberculosis: pulmonary form.
- Extrapulmonary tuberculosis: involvement of the osteoarticular and urogenital systems, skin, central nervous system, and abdominal organs.
Briefly: answers to topical questions
Which antituberculosis drugs belong to first-line (primary) agents?
First-line (primary) antituberculosis agents include:
- Isoniazid;
- Rifampicin;
- Pyrazinamide;
- Ethambutol;
- Streptomycin.
They are used for newly diagnosed tuberculosis if the pathogen is susceptible to these drugs.
What is the mechanism of action of isoniazid on Mycobacterium tuberculosis?
The mechanism of action of isoniazid involves the inhibition of mycolic acid synthesis. These acids are a specific component of the cell wall of Mycobacterium tuberculosis. Host (human) cells lack mycolic acids, which ensures high selectivity of the drug's action: it is highly toxic to mycobacteria and low in toxicity to humans.
What specific adverse effects does rifampicin cause?
Rifampicin causes a number of specific and systemic adverse effects.
- Discoloration of body fluids — urine, saliva, and tears turn orange.
- Hepatotoxicity — liver function impairment, risk of hepatitis.
- Hematological disorders — thrombocytopenia and anemia.
- Nephrotoxicity — risk of renal failure.
- «Flu-like syndrome» — fever, arthralgia, and myalgia.
- Gastrointestinal disorders — dyspepsia, nausea, vomiting, diarrhea.
Which antituberculosis drugs belong to reserve (second-line) agents?
Reserve antituberculosis agents (second-line drugs) include medications prescribed when mycobacteria are resistant to primary agents.
- Prothionamide and ethionamide — isonicotinic acid thioamide derivatives.
- Kanamycin and amikacin — aminoglycoside antibiotics.
- Lomefloxacin and other fluoroquinolones — synthetic antibacterial agents.
- Capreomycin (Capreomycin) and florimycin — polypeptide antibiotics.
- Cycloserine, rifabutin, and aminosalicylic acid — other reserve agents.
What is the mechanism of action of aminoglycosides in the treatment of tuberculosis?
The mechanism of action of aminoglycosides in the treatment of tuberculosis involves the inhibition of protein synthesis. Aminoglycosides exert a bactericidal effect.
To remember the classification, keep this association in mind: antibiotics are divided into aminoglycosides (streptomycin, kanamycin, amikacin) and others (rifampicin, cycloserine), while synthetic agents are divided into INH derivatives (isoniazid), PAS, and thioamides.
Class and exam questions
Why are conventional antibiotics largely ineffective against Koch's bacillus?
This is due to the slow growth and delayed metabolism of mycobacteria, the high lipid content in their cell wall, and the intracellular localization of the pathogen.
What are the main principles of tuberculosis treatment?
Therapy must be prolonged (from 6 months to a year or more) and necessarily combined to prevent the development of drug resistance.
Which drug groups are included in the modern arsenal of antituberculosis agents?
The arsenal is divided into antibiotics (including aminoglycosides and rifampicin) and synthetic agents (INH, PAS, and isonicotinic acid thioamide derivatives).
What else to study on this topic
- History of the discovery of the first antituberculosis drug by Selman Waksman
- Detailed pharmacological profile of aminoglycosides
- Isonicotinic acid hydrazide derivatives and their features
- Properties of p-aminosalicylic acid (PAS) derivatives
- Extrapulmonary forms of tuberculosis and their specific lesions
Master the entire topic in the «Pharmacology» course
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