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Questions and Answers
What is the mechanism of action of isoniazid?
What is the mechanism of action of isoniazid?
What is the typical daily dosage of isoniazid for an adult?
What is the typical daily dosage of isoniazid for an adult?
Which of the following adverse effects is associated with isoniazid?
Which of the following adverse effects is associated with isoniazid?
Which physiological condition may predispose patients to increased toxicity from isoniazid?
Which physiological condition may predispose patients to increased toxicity from isoniazid?
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What is the primary mechanism of action of rifampin?
What is the primary mechanism of action of rifampin?
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What is a potential effect when isoniazid promotes the excretion of pyridoxine?
What is a potential effect when isoniazid promotes the excretion of pyridoxine?
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In which condition may rifampin achieve adequate cerebrospinal fluid concentration?
In which condition may rifampin achieve adequate cerebrospinal fluid concentration?
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What is a major difference between isoniazid and rifampin in terms of their pharmacokinetics?
What is a major difference between isoniazid and rifampin in terms of their pharmacokinetics?
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What type of bacteria are Mycobacteria?
What type of bacteria are Mycobacteria?
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Which is NOT a common outcome after inhalation of Mycobacterium tuberculosis?
Which is NOT a common outcome after inhalation of Mycobacterium tuberculosis?
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Which of the following organs is most commonly infected by tuberculosis?
Which of the following organs is most commonly infected by tuberculosis?
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Why is a four-drug regimen used in TB therapy?
Why is a four-drug regimen used in TB therapy?
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Which drug is primarily responsible for providing coverage against resistant Mycobacterium tuberculosis strains?
Which drug is primarily responsible for providing coverage against resistant Mycobacterium tuberculosis strains?
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What is the nature of Isoniazid as a drug?
What is the nature of Isoniazid as a drug?
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What is the mechanism of action for P-Aminosalicylic Acid?
What is the mechanism of action for P-Aminosalicylic Acid?
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Which of the following describes how Mycobacteria can develop resistance?
Which of the following describes how Mycobacteria can develop resistance?
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What is the primary mechanism by which pyrazinamide exerts its activity against mycobacteria?
What is the primary mechanism by which pyrazinamide exerts its activity against mycobacteria?
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Which of the following is a common adverse effect of P-Aminosalicylic Acid?
Which of the following is a common adverse effect of P-Aminosalicylic Acid?
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Which fluoroquinolone antibiotic is known for its effectiveness against resistant strains?
Which fluoroquinolone antibiotic is known for its effectiveness against resistant strains?
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Which of the following adverse effects is primarily associated with ethambutol?
Which of the following adverse effects is primarily associated with ethambutol?
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What is the drug of choice for Mycobacterium avium complex (MAC) infections?
What is the drug of choice for Mycobacterium avium complex (MAC) infections?
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Which drug is a potent inducer of cytochrome P450?
Which drug is a potent inducer of cytochrome P450?
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What is a significant consideration when using rifampin in patients?
What is a significant consideration when using rifampin in patients?
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What is the primary action of bedaquiline in mycobacteria?
What is the primary action of bedaquiline in mycobacteria?
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Why is ethambutol typically always given in combination with other anti-tuberculous drugs?
Why is ethambutol typically always given in combination with other anti-tuberculous drugs?
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Which mycobacterium is known to be completely resistant to pyrazinamide?
Which mycobacterium is known to be completely resistant to pyrazinamide?
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What role does clofazimine play in the treatment of leprosy?
What role does clofazimine play in the treatment of leprosy?
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What are the potential adverse effects associated with pyrazinamide usage?
What are the potential adverse effects associated with pyrazinamide usage?
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What is the optimal dosage of ethambutol when treating tuberculous meningitis in adults?
What is the optimal dosage of ethambutol when treating tuberculous meningitis in adults?
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Leprosy primarily affects which of the following?
Leprosy primarily affects which of the following?
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What serious adverse effect is most likely to occur with a prolonged dose of ethambutol at 25 mg/kg/day?
What serious adverse effect is most likely to occur with a prolonged dose of ethambutol at 25 mg/kg/day?
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What dosage of drug is associated with rare visual disturbances?
What dosage of drug is associated with rare visual disturbances?
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What is a significant risk associated with Streptomycin when considering its adverse effects?
What is a significant risk associated with Streptomycin when considering its adverse effects?
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Which drug is contraindicated in patients who are epileptic?
Which drug is contraindicated in patients who are epileptic?
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Which of the following statements about Capreomycin is true?
Which of the following statements about Capreomycin is true?
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Which alternative drug is typically avoided due to its poor tolerance profile?
Which alternative drug is typically avoided due to its poor tolerance profile?
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What is the main mechanism of action for aminoglycosides like Streptomycin?
What is the main mechanism of action for aminoglycosides like Streptomycin?
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In which instance would second-line drugs be considered?
In which instance would second-line drugs be considered?
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What type of toxicity is commonly associated with Aminoglycosides like Kanamycin and Amikacin?
What type of toxicity is commonly associated with Aminoglycosides like Kanamycin and Amikacin?
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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
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The first line of drugs for treatment of TB usually includes four drugs:
- Isoniazid (INH)
- Rifampin
- Rifabutin
- Rifapentine
- Rifampicin
- Ethambutol
- Pyrazinamide
- Streptomycin
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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
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Ethionamide: A nicotinamide derivative used in TB treatment; poorly tolerated due to gastric irritation, neurological symptoms, and hepatotoxicity.
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Capreomycin: An aminoglycoside that is important for treating drug-resistant TB. It is nephrotoxic and ototoxic.
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Cycloserine: A GABA transaminase inhibitor that acts as a cell wall synthesis inhibitor.
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Adverse effects include peripheral neuropathy, and CNS dysfunction (with depression and psychotic reactions.
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Pyridoxine should be provided in accordance with treatment protocols.
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Kanamycin & Amikacin: Used in multi-drug-resistant TB, serve as an alternative to streptomycin.
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Ciprofloxacin & Levofloxacin: Fluoroquinolone antibiotics, effective against both typical and atypical mycobacteria, are used against resistant strains.
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Rifapentine: Similar to rifampicin, it is an RNA polymerase inhibitor, exhibits cross-resistance with rifampicin. It is a potent inducer of cytochrome p450.
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P-aminosalicylic acid (PAS): Similar to sulfonamides and p-aminobenzoic acid; inhibits folate synthesis and mycobactin synthesis (cell wall component).
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Bedaquiline: Effective against mycobacteria; inhibits adenosine 5'-triphosphate (ATP) synthase.
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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
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Isoniazid: Peripheral neuropathy, hepatitis, hypersensitivity reactions (such as fever and skin rash). Pyridoxine (vitamin B6) supplements may help mitigate some of these symptoms.
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Rifampin: Harmless red-orange discoloration of urine, sweat, tears, and contact lenses; rashes; thrombocytopenia; nephritis; cholestatic jaundice; hepatitis; flu-like syndrome; CYP p450 inducer.
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Pyrazinamide: Hepatotoxicity, nausea, vomiting, and drug fever are possible adverse effects
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Ethambutol: Retrobulbar neuritis is a common, serious side effect that can lead to visual impairment.
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Streptomycin: Dose-related toxicity; ototoxic and nephrotoxic effects; vertigo and hearing loss can be permanent.
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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.