Tuberculosis Flashcards
What is tuberculosis (TB)?
Tuberculosis is a disease caused by Mycobacterium tuberculosis, primarily affecting the lungs but can affect other organs. It is the leading cause of death from a single infectious agent, surpassing HIV.
How is TB transmitted?
TB is spread through airborne droplets containing Mycobacterium tuberculosis. Inhalation of these droplets can lead to infection.
What are the symptoms of TB?
Symptoms include weight loss, loss of appetite, night sweats, fever, fatigue, chills, coughing, and chest pain.
What are the types of TB?
Drug-sensitive TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB).
What makes Mycobacterium tuberculosis unique?
It has a lipid-rich cell wall with mycolic acid, making it waxy and resistant to digestion. It grows slowly, dividing every 15-20 hours, and has intrinsic resistance to most antibiotics.
What are the primary aims of TB treatment?
To cure the patient, minimize risk of death and disability, prevent relapse, decrease transmission, and prevent acquired resistance.
What is the first-line treatment for drug-sensitive TB?
A combination of isoniazid, rifampicin, ethambutol, or streptomycin, and pyrazinamide, taken daily for at least 6 months.
How does isoniazid work?
Isoniazid inhibits the synthesis of mycolic acid, a critical component of the mycobacterial cell wall. It is a pro-drug activated by the catalase-peroxidase enzyme KatG and is bactericidal against actively dividing bacteria.
What causes resistance to isoniazid?
Resistance is primarily due to mutations in the KatG gene, which prevents activation of the pro-drug. Mutations in InhA can also reduce binding of the drug to its target.
What are the adverse effects of isoniazid?
Adverse effects include hepatitis, particularly in older individuals and alcoholics, due to toxic metabolites formed by CYP450 enzymes. Nerve damage can also occur due to pyridoxine depletion.
How does rifampicin work?
Rifampicin inhibits DNA-dependent RNA polymerase, preventing RNA synthesis. It is well-distributed in tissues, body fluids, and cerebrospinal fluid.
What is the mechanism of pyrazinamide?
Pyrazinamide is a pro-drug activated in acidic conditions. It disrupts membrane potential and energy production in Mycobacterium tuberculosis.
What causes resistance to pyrazinamide?
Resistance arises from impaired uptake or mutations in the pyrazinamidase enzyme (pncA), which prevents activation of the pro-drug.
How does ethambutol work?
Ethambutol inhibits the enzyme arabinosyl transferase, disrupting arabinogalactan synthesis, which leads to increased cell wall permeability. It is bacteriostatic.
What is MDR-TB?
Multidrug-resistant TB is caused by strains of M. tuberculosis resistant to at least both isoniazid and rifampicin, requiring prolonged and complex treatment.
What is XDR-TB?
Extensively drug-resistant TB is resistant to isoniazid, rifampin, any fluoroquinolone, and at least one Group 2 parenteral second-line agent, such as aminoglycosides. It has high mortality rates.
What is bedaquiline and how does it work?
Bedaquiline is a novel anti-TB agent that inhibits mycobacterial ATP synthetase, making it effective against resistant isolates. It is used for MDR-TB.
Why was bedaquiline approved despite risks?
It was approved due to the high risk of fatal outcomes and the spread of resistance associated with inadequate TB treatment. The benefit-risk balance justified its use.
What are the challenges in TB treatment?
Challenges include slow development of new drugs, lack of rapid diagnostics, poor treatment compliance, and ongoing resistance. Vaccine trials are underway.
