Antimycobacterial Drugs and Tuberculosis
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Questions and Answers

What is the mechanism of action of isoniazid?

  • Inhibiting bacterial cell wall synthesis
  • Blocking mycolic acid synthesis (correct)
  • Inhibiting DNA synthesis
  • Promoting protein synthesis
  • What is the typical daily dosage of isoniazid for an adult?

  • 900 mg
  • 300 mg (correct)
  • 150 mg
  • 600 mg
  • Which of the following adverse effects is associated with isoniazid?

  • Rheumatoid arthritis
  • Hepatitis (correct)
  • Increased urination
  • Hypotension
  • Which physiological condition may predispose patients to increased toxicity from isoniazid?

    <p>Malnutrition</p> Signup and view all the answers

    What is the primary mechanism of action of rifampin?

    <p>Inhibition of RNA synthesis</p> Signup and view all the answers

    What is a potential effect when isoniazid promotes the excretion of pyridoxine?

    <p>Peripheral neuropathy</p> Signup and view all the answers

    In which condition may rifampin achieve adequate cerebrospinal fluid concentration?

    <p>Meningeal inflammation</p> Signup and view all the answers

    What is a major difference between isoniazid and rifampin in terms of their pharmacokinetics?

    <p>Isoniazid is readily absorbed from the gastrointestinal tract</p> Signup and view all the answers

    What type of bacteria are Mycobacteria?

    <p>Gram-positive, non-motile, non-spore forming rods</p> Signup and view all the answers

    Which is NOT a common outcome after inhalation of Mycobacterium tuberculosis?

    <p>Viral infection</p> Signup and view all the answers

    Which of the following organs is most commonly infected by tuberculosis?

    <p>Lungs</p> Signup and view all the answers

    Why is a four-drug regimen used in TB therapy?

    <p>To ensure maximum effectiveness and address potential resistance</p> Signup and view all the answers

    Which drug is primarily responsible for providing coverage against resistant Mycobacterium tuberculosis strains?

    <p>Streptomycin</p> Signup and view all the answers

    What is the nature of Isoniazid as a drug?

    <p>A prodrug with efficacy against both extracellular and intracellular organisms</p> Signup and view all the answers

    What is the mechanism of action for P-Aminosalicylic Acid?

    <p>Inhibits folate synthesis</p> Signup and view all the answers

    Which of the following describes how Mycobacteria can develop resistance?

    <p>By residing within macrophages</p> Signup and view all the answers

    What is the primary mechanism by which pyrazinamide exerts its activity against mycobacteria?

    <p>Disrupting cell membrane metabolism</p> Signup and view all the answers

    Which of the following is a common adverse effect of P-Aminosalicylic Acid?

    <p>Crystalluria</p> Signup and view all the answers

    Which fluoroquinolone antibiotic is known for its effectiveness against resistant strains?

    <p>Ciprofloxacin</p> Signup and view all the answers

    Which of the following adverse effects is primarily associated with ethambutol?

    <p>Retrobulbar neuritis</p> Signup and view all the answers

    What is the drug of choice for Mycobacterium avium complex (MAC) infections?

    <p>Rifabutin</p> Signup and view all the answers

    Which drug is a potent inducer of cytochrome P450?

    <p>Rifapentine</p> Signup and view all the answers

    What is a significant consideration when using rifampin in patients?

    <p>It may cause harmless red-orange discoloration</p> Signup and view all the answers

    What is the primary action of bedaquiline in mycobacteria?

    <p>Inhibiting ATP synthase</p> Signup and view all the answers

    Why is ethambutol typically always given in combination with other anti-tuberculous drugs?

    <p>To prevent drug resistance</p> Signup and view all the answers

    Which mycobacterium is known to be completely resistant to pyrazinamide?

    <p>Mycobacterium kansasii</p> Signup and view all the answers

    What role does clofazimine play in the treatment of leprosy?

    <p>It is an antimycobacterial agent</p> Signup and view all the answers

    What are the potential adverse effects associated with pyrazinamide usage?

    <p>Gastrointestinal distress and hyperuricemia</p> Signup and view all the answers

    What is the optimal dosage of ethambutol when treating tuberculous meningitis in adults?

    <p>50 mg/kg twice weekly</p> Signup and view all the answers

    Leprosy primarily affects which of the following?

    <p>Skin and peripheral nerves</p> Signup and view all the answers

    What serious adverse effect is most likely to occur with a prolonged dose of ethambutol at 25 mg/kg/day?

    <p>Retrobulbar neuritis</p> Signup and view all the answers

    What dosage of drug is associated with rare visual disturbances?

    <p>15 mg/kg/d</p> Signup and view all the answers

    What is a significant risk associated with Streptomycin when considering its adverse effects?

    <p>Ototoxicity</p> Signup and view all the answers

    Which drug is contraindicated in patients who are epileptic?

    <p>Cycloserine</p> Signup and view all the answers

    Which of the following statements about Capreomycin is true?

    <p>It may cause local pain and sterile abscesses.</p> Signup and view all the answers

    Which alternative drug is typically avoided due to its poor tolerance profile?

    <p>Ethionamide</p> Signup and view all the answers

    What is the main mechanism of action for aminoglycosides like Streptomycin?

    <p>Protein synthesis inhibitor</p> Signup and view all the answers

    In which instance would second-line drugs be considered?

    <p>In cases of alternative drug resistance</p> Signup and view all the answers

    What type of toxicity is commonly associated with Aminoglycosides like Kanamycin and Amikacin?

    <p>Ototoxicity</p> Signup and view all the answers

    Study Notes

    Antimycobacterial Drugs

    • Mycobacteria are inherently resistant to most antibiotics.
    • They are Gram-positive, non-motile, non-spore-forming rod-shaped bacteria.
    • Intracellular pathogens residing within macrophages are inaccessible to drugs that penetrate poorly.
    • Mycobacteria develop resistance.
    • The cell wall of Mycobacteria is rich in lipids, primarily mycolic acids. This complex structure is crucial to their resistance.
    • The cell wall also has arabinogalactan and peptidoglycan layers.
    • Response to chemotherapy for mycobacterial infections is slow, requiring treatment for months to years.

    Tuberculosis (TB)

    • Tuberculosis is caused by Mycobacterium tuberculosis.
    • It can damage various parts of the body, but primarily attacks the lungs.
    • TB spreads through the air via coughs, sneezes, or talking.
    • Inhalation of M. tuberculosis and deposition in the lungs can lead to one of four outcomes:
      • Immediate clearance of the organism.
      • Primary disease (rapid progression to active disease).
      • Latent infection (with or without subsequent reactivation disease).
      • Reactivation disease (onset of active disease after a period of latent infection).
    • Infection does not automatically lead to active disease.
    • TB bacteria can enter a hibernation-like state, remaining dormant for decades.
    • Infection can be exacerbated by weakened immune systems. Specific populations such as infants or the elderly, are more vulnerable.
    • Common organs affected by TB are the lungs (90% of cases), the genitourinary tract, skeleton, and meninges.

    1st Line Drugs

    • The first line of drugs for treatment of TB usually includes four drugs:

      • Isoniazid (INH)
      • Rifampin
      • Rifabutin
      • Rifapentine
      • Rifampicin
      • Ethambutol
      • Pyrazinamide
      • Streptomycin
    • In clinical practice, therapy is initiated with a four-drug regimen consisting of isoniazid, rifampin, pyrazinamide and either ethambutol or streptomycin.

    Drug Regimen Duration

    • The duration of therapy depends on the specific drug regimen:
      • Isoniazid, rifampin, pyrazinamide = 6 months
      • Isoniazid, rifampin = 9 months
      • Rifampin, ethambutol, pyrazinamide = 6 months
      • Rifampin, ethambutol = 12 months
      • Isoniazid, ethambutol = 18 months
      • Others = ≥ 24 months

    Isoniazid (INH)

    • MOA: Inhibits the synthesis of mycolic acid (an essential component of mycobacterial cell walls)
    • Is a prodrug that requires activation by mycobacterial catalase-peroxidase (KatG).
    • Active against both extracellular and intracellular organisms.
    • It may be given orally in a dose of 5mg/kg or 300mg, but doses could be higher up to 10mg/kg to address severe cases

    Rifampin

    • MOA: Binds strongly to bacterial RNA polymerase, inhibiting RNA synthesis.
    • Effective against various "typical" bacteria.

    Pyrazinamide

    • MOA: Disrupts mycobacterial cell membrane metabolism and transport functions within macrophages.
    • Active in an acidic environment of lysosomes.

    Ethambutol

    • MOA: Inhibits mycobacterial arabinosyl transferases, which are involved in arabinoglycan synthesis (an essential component of the mycobacterial cell wall).

    Streptomycin

    • MOA: An aminoglycoside that penetrates cells poorly; primarily effective against extracellular mycobacteria.
    • Achieves therapeutic concentrations in inflamed meninges.

    Other Second-line Drugs

    • Ethionamide: A nicotinamide derivative used in TB treatment; poorly tolerated due to gastric irritation, neurological symptoms, and hepatotoxicity.

    • Capreomycin: An aminoglycoside that is important for treating drug-resistant TB. It is nephrotoxic and ototoxic.

    • Cycloserine: A GABA transaminase inhibitor that acts as a cell wall synthesis inhibitor.

    • Adverse effects include peripheral neuropathy, and CNS dysfunction (with depression and psychotic reactions.

    • Pyridoxine should be provided in accordance with treatment protocols.

    • Kanamycin & Amikacin: Used in multi-drug-resistant TB, serve as an alternative to streptomycin.

    • Ciprofloxacin & Levofloxacin: Fluoroquinolone antibiotics, effective against both typical and atypical mycobacteria, are used against resistant strains.

    • Rifapentine: Similar to rifampicin, it is an RNA polymerase inhibitor, exhibits cross-resistance with rifampicin. It is a potent inducer of cytochrome p450.

    • P-aminosalicylic acid (PAS): Similar to sulfonamides and p-aminobenzoic acid; inhibits folate synthesis and mycobactin synthesis (cell wall component).

    • Bedaquiline: Effective against mycobacteria; inhibits adenosine 5'-triphosphate (ATP) synthase.

    • Pretomanid: Approved for the treatment of multi-drug-resistant TB.

    Clinical Use

    • Antimycobacterial therapy is predominantly used for treating mycobacterial infections in individuals with TB, including latent TB.
    • Also used to treat Mycobacterium kansasii (or M.kansasii), a pulmonary condition similar to TB.

    Adverse Effects

    • Isoniazid: Peripheral neuropathy, hepatitis, hypersensitivity reactions (such as fever and skin rash). Pyridoxine (vitamin B6) supplements may help mitigate some of these symptoms.

    • Rifampin: Harmless red-orange discoloration of urine, sweat, tears, and contact lenses; rashes; thrombocytopenia; nephritis; cholestatic jaundice; hepatitis; flu-like syndrome; CYP p450 inducer.

    • Pyrazinamide: Hepatotoxicity, nausea, vomiting, and drug fever are possible adverse effects

    • Ethambutol: Retrobulbar neuritis is a common, serious side effect that can lead to visual impairment.

    • Streptomycin: Dose-related toxicity; ototoxic and nephrotoxic effects; vertigo and hearing loss can be permanent.

    • Other drugs have their specific adverse effects.

    Additional Information

    • Mycobacterium Avium Complex (MAC): Common in patients with HIV. Treatment commonly includes Azithromycin or Clarithromycin, plus Ethambutol, possibly combined with a third agent such as Ciprofloxacin, or Rifabutin.

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    Description

    This quiz covers the characteristics of mycobacteria, including their resistance to antibiotics and the structure of their cell walls. Additionally, it explores tuberculosis caused by Mycobacterium tuberculosis, its transmission, and potential outcomes after infection. Test your knowledge on these important medical topics.

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