Tuberculosis 2
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Questions and Answers

What is the recommended dose of isoniazid for tuberculosis meningitis?

  • 35 mg/kg
  • 22.5-30 mg/kg
  • 10 mg/kg
  • 15-20 mg/kg (correct)

Which regimen is recommended for rifampicin-susceptible, isoniazid-resistant tuberculosis?

  • Bedaquiline, levofloxacin, clofazimine for 6 months
  • Rifampicin, ethambutol, pyrazinamide, and levofloxacin for 4 months
  • Rifampicin, ethambutol, pyrazinamide, and levofloxacin for 6 months (correct)
  • Linezolid, clofazimine, ethionamide for 12 months

What is the duration of treatment for pulmonary tuberculosis?

  • 6-9 months
  • 12 months
  • 2-3 months
  • 4-6 months (correct)

For patients with multidrug- or rifampicin-resistant tuberculosis, what is the shorter regimen?

<p>Bedaquiline, levofloxacin, clofazimine, ethambutol for 4-6 months (D)</p> Signup and view all the answers

Which of the following is NOT a criterion for the BPAL regimen in resistant tuberculosis?

<p>Recent exposure to ethambutol (A)</p> Signup and view all the answers

Which drug is not part of the longer regimen for multidrug- or rifampicin-resistant tuberculosis?

<p>Ethionamide (B)</p> Signup and view all the answers

What is the maximum recommended dosage of pyrazinamide for tuberculosis meningitis?

<p>45 mg/kg (B)</p> Signup and view all the answers

What is the recommended dose range for the medication mentioned?

<p>15mg/kg 750-1500mg (B)</p> Signup and view all the answers

What precaution should be taken regarding the use of hepatotoxic drugs?

<p>They may worsen hepatic impairment and increase hepatotoxicity risk. (B)</p> Signup and view all the answers

Which of the following is a common side effect of the medication?

<p>Dizziness (A)</p> Signup and view all the answers

How should aluminum-, calcium-, or magnesium-containing antacids be managed in relation to TB drug administration?

<p>They should be taken 4 hours before or after TB drug administration. (A)</p> Signup and view all the answers

What is a key reason for educating patients about their TB treatment and potential adverse effects?

<p>To improve treatment adherence and outcomes. (C)</p> Signup and view all the answers

What is the maximum recommended dose of rifampicin for adults?

<p>600 mg (C)</p> Signup and view all the answers

Which of the following side effects is most commonly associated with pyrazinamide?

<p>Polyarthralgia (B)</p> Signup and view all the answers

What is the primary mode of action of ethambutol?

<p>Inhibits incorporation of mycolic acid (B)</p> Signup and view all the answers

What potential interaction should be considered when taking rifampicin?

<p>Induces CYP enzymes (C)</p> Signup and view all the answers

When should pyrazinamide be avoided?

<p>In acute gout (A)</p> Signup and view all the answers

How does food affect the bioavailability of rifampicin?

<p>Decreases bioavailability (B)</p> Signup and view all the answers

What is the common practice for dosing rifampicin in terms of weight?

<p>Based on total body weight (A)</p> Signup and view all the answers

Which of the following is a significant precaution when using ethambutol?

<p>Optic neuritis (D)</p> Signup and view all the answers

What symptom may occur due to rifampicin’s side effects?

<p>Orange-red coloration of body fluids (A)</p> Signup and view all the answers

What is the maximum dose of pyrazinamide for adults?

<p>2 g (C)</p> Signup and view all the answers

What is the primary mode of action of bedaquiline?

<p>Inhibits the c subunit of ATP synthase (C)</p> Signup and view all the answers

Which of the following is a precaution when using bedaquiline?

<p>QT prolongation due to blocking hERG channel (B)</p> Signup and view all the answers

What is a significant side effect of pretomanid?

<p>Loss of appetite (C)</p> Signup and view all the answers

How should bedaquiline be administered to ensure good bioavailability?

<p>With food (B)</p> Signup and view all the answers

What is the dosing regimen for pretomanid?

<p>200mg once daily for 26 weeks (C)</p> Signup and view all the answers

Which drug interacts as a CYP3A4 substrate?

<p>Both A and C (A)</p> Signup and view all the answers

What is the mechanism through which linezolid operates?

<p>Binding to 23S ribosomal RNA of the 50S subunit (C)</p> Signup and view all the answers

Which adverse effect is specifically associated with linezolid?

<p>Anaemia and thrombocytopenia (B)</p> Signup and view all the answers

What leads to the delayed effect of bedaquiline observed from day 4 onward?

<p>The bacteria's ATP storage allowing for initial survival (C)</p> Signup and view all the answers

What is the primary mode of action of isoniazid?

<p>Inhibiting synthesis of mycolic acids (D)</p> Signup and view all the answers

What is a common side effect of isoniazid treatment?

<p>Hepatitis (B)</p> Signup and view all the answers

Which factor increases the risk of peripheral neuropathy in patients taking isoniazid?

<p>Severe malnutrition (B)</p> Signup and view all the answers

In which group are fast acetylators at a higher risk during isoniazid treatment?

<p>Increased risk of treatment failure due to low isoniazid levels (D)</p> Signup and view all the answers

What is the normal daily dose of isoniazid for adults?

<p>5 mg/kg (B)</p> Signup and view all the answers

What is the action of rifampicin against M. tuberculosis?

<p>Inhibiting bacterial RNA polymerase (A)</p> Signup and view all the answers

For slow acetylators, what is the suggested daily dose of isoniazid?

<p>2.5 mg/kg (B)</p> Signup and view all the answers

Which of the following is a precaution for isoniazid administration?

<p>Severe malnutrition (D)</p> Signup and view all the answers

What role does N-Acetyltransferase 2 play in the metabolism of isoniazid?

<p>It activates isoniazid to its effective form (C)</p> Signup and view all the answers

What is the maximum dose of isoniazid for adults?

<p>300 mg (A)</p> Signup and view all the answers

Flashcards

TB Meningitis Dosage

Higher doses of TB drugs (isoniazid, rifampicin, pyrazinamide) are used for a longer duration (6-9 months) compared to pulmonary TB (4-6 months).

MDR/RR-TB Shorter Regimen

A shorter regimen (4-6 months) for MDR/RR-TB that uses specific drugs like Bedaquiline, levofloxacin/moxifloxacin, clofazimine, pyrazinamide, ethambutol, high-dose isoniazid, ethionamide.

MDR/RR-TB Longer Regimen

A longer regimen (6 months initial, 12 months continuation) for MDR/RR-TB that involves Bedaquiline, levofloxacin/moxifloxacin, linezolid, clofazimine/cycloserine.

BPAL Regimen

A specific regimen (6-9 months) for MDR/RR-TB with fluoroquinolone resistance that includes Bedaquiline, pretomanid, and linezolid.

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tb Isoniazid Dosage (Pulmonary)

10 mg per kg TBW for pulmonary TB

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tb Rifampicin Dosage (Pulmonary)

15 mg per kg TBW for pulmonary TB

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TB Meningitis Isoniazid Dosage

15-20 mg per kg TBW

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Bedaquiline Mode of Action

Inhibits the c subunit of ATP synthase, crucial for ATP generation in tuberculosis bacteria.

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Bedaquiline Dose

400 mg once daily for two weeks, then 200 mg three times a week.

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Bedaquiline Precaution

Causes QT prolongation, potentially blocking a certain heart channel (hERG).

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Bedaquiline Side Effects

Common side effects include nausea, headache, joint pain, chest pain, & possible liver problems (more than 1%).

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Pretomanid Mode of Action

A prodrug activated by nitroreductases to increase nitric oxide for bactericidal effects, especially in low-oxygen environments.

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Pretomanid Dose

200 mg once daily for 26 weeks.

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Pretomanid Usage Limitation

Must be part of a specific combination therapy (BPAL) for effectiveness.

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Linezolid Mode of Action

Binds to bacterial RNA, preventing essential processes for bacterial reproduction.

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Linezolid Precaution

Possible side effects include blood disorders (anemia, low platelets), nerve damage, and metabolic problems.

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Isoniazid Mode of Action

Inhibits mycolic acid synthesis in the mycobacterial cell wall, killing actively dividing M. tuberculosis and inhibiting resting bacteria.

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Isoniazid Dose (Adults)

5 mg/kg once daily, maximum 300 mg.

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Isoniazid Precautions

Increased risk of peripheral neuropathy in malnutrition, diabetes, HIV infection, and alcoholism. Use pyridoxine as prophylaxis.

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N-Acetylation Polymorphism

Variations in the N-Acetyltransferase 2 gene affect how the body processes isoniazid, leading to rapid, intermediate, or slow acetylator phenotypes.

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Fast Acetylators (Isoniazid)

Higher risk of treatment failure due to lower isoniazid levels.

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Slow Acetylators (Isoniazid)

Higher risk of side effects due to higher isoniazid levels.

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Rifampicin Mode of Action

Inhibits bacterial RNA polymerase, killing rapidly dividing M. tuberculosis and affecting those in a semi-dormant state.

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Risk Factors for Isoniazid Reactions

Malnutrition, diabetes, HIV infection, and alcoholism increase the risk of peripheral neuropathy.

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Common Isoniazid Side Effects

Hepatitis (increased liver enzymes), rash, fever, and peripheral neuritis are possible adverse effects.

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Rifampicin Dosage Adjustment (TB)

No specific dosing information for TB.

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TB Drug Dosing

TB treatment requires the right drug dose to prevent treatment failure and side effects. It involves monitoring patient response, and minimizing toxicity through proper screening.

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TB Drug Toxicity

TB drugs can have negative side effects (toxicity), which should be prevented and managed to avoid harm and improve treatment adherence.

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Patient Counseling (TB)

Patients should receive education about their TB treatment, including potential side effects, to maximize treatment success.

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Adverse Effects (AE)

Unwanted reactions or problems that occur as a result of TB treatment.

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Pharmacotherapy (TB)

Drug therapy for Tuberculosis, involving appropriate dosing, monitoring, and preventative measures for side effects.

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Rifampicin Dose (Adults)

Once daily, 10 mg/kg, maximum 600 mg.

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Rifampicin Hepatotoxicity Risk

May worsen liver problems; hepatotoxic drugs increase the risk.

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Rifampicin Side Effects

Arthralgia, myalgia (early), headache, dizziness, drowsiness, ataxia, confusion, fatigue, orange-red body fluids.

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Rifampicin Drug Interactions

Induces various enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, UGT, Pgp).

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Rifampicin Food Interaction

Food reduces absorption; take on an empty stomach.

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High Dose Rifampicin

Studies explore higher dosages (35-40 mg/kg) to reduce treatment duration.

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Pyrazinamide Mode of Action

Bactericidal against M. tuberculosis at low pH; active within macrophages.

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Pyrazinamide Dose (Adults)

Once daily, 20-25 mg/kg, maximum 2 g.

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Ethambutol Mode of Action

May inhibit mycolic acid incorporation, bacteriostatic against M. tuberculosis.

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Ethambutol Dose (Adults)

Once daily, 15-20 mg/kg.

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Study Notes

Tuberculosis Treatment Regimens

  • Isoniazid: The recommended dose for tuberculosis meningitis is 10 mg/kg/day, up to a maximum of 900 mg/day.
  • Rifampicin-Susceptible, Isoniazid-Resistant Tuberculosis: The recommended regimen for rifampicin-susceptible, isoniazid-resistant tuberculosis involves a combination of rifampicin, pyrazinamide, ethambutol, and a fluoroquinolone (e.g., levofloxacin) for 2 months, followed by rifampicin, pyrazinamide, and ethambutol for 4 months.
  • Duration of Treatment for Pulmonary Tuberculosis: The standard duration of treatment for pulmonary tuberculosis is 6 months.
  • Shorter Regimen for Multidrug-Resistant Tuberculosis: For patients with multidrug- or rifampicin-resistant tuberculosis, a shorter regimen can be used, for example, 9 months, involving a combination of bedaquiline, pretomanid, and linezolid.
  • BPAL Regimen Criterion: The BPAL regimen (Bedaquiline, Pretomanid, Linezolid, and Amikacin) requires a minimum of one drug with activity against M. tuberculosis and resistance to both rifampicin and isoniazid.

Specific Drug Considerations and Precautions

  • Longer Regimen for Multidrug-Resistant Tuberculosis: The longer regimen for multidrug- or rifampicin-resistant tuberculosis does not include pretomanid.
  • Pyrazinamide Dosing: The maximum recommended dosage of pyrazinamide for tuberculosis meningitis is 2 grams/day.
  • Pyrazinamide Dose Range: The recommended dose range for pyrazinamide for adults is 15-30 mg/kg/day.
  • Hepatotoxic Drugs: Monitor liver function tests closely when using hepatotoxic drugs like pyrazinamide and rifampicin.
  • Common Side Effect of Pyrazinamide: A common side effect of pyrazinamide is arthralgia (joint pain).
  • Antacids and TB Drugs: Administer aluminum-, calcium-, or magnesium-containing antacids at least 2 hours before or 4 hours after TB drug administration.
  • Patient Education: Educate patients about their TB treatment and potential adverse effects to ensure adherence and early detection of problems.
  • Rifampicin Maximum Dose: The maximum recommended dose of rifampicin for adults is 600 mg/day.
  • Ethambutol Mode of Action: Ethambutol’s primary mode of action is inhibiting the synthesis of arabinogalactan, a cell wall component of Mycobacterium tuberculosis.
  • Rifampicin Interaction: Consider potential interactions with rifampicin, which can induce the metabolism of certain drugs, affecting their efficacy.
  • Pyrazinamide Avoidance: Avoid the use of pyrazinamide during pregnancy, as it may be teratogenic.
  • Food and Rifampicin Bioavailability: Food does not significantly affect the bioavailability of rifampicin.
  • Rifampicin Dosing: Rifampicin is typically dosed based on body weight, with a common dose of 10 mg/kg/day.
  • Ethambutol Precaution: A significant precaution when using ethambutol is monitoring for optic neuritis, a potentially serious side effect.
  • Rifampicin Side Effect: A side effect of rifampicin can be orange discoloration of urine, sweat, and tears.
  • Pyrazinamide Maximum Dose: The maximum dose of pyrazinamide for adults is 2 g/day.
  • Bedaquiline Mode of Action: The primary mode of action of bedaquiline is the inhibition of ATP synthase, leading to disruption of bacterial energy production.
  • Bedaquiline Precaution: A precaution when using bedaquiline is the risk of prolongation of the QT interval on the electrocardiogram (ECG).
  • Pretomanid Side Effect: A significant side effect of pretomanid is peripheral neuropathy.
  • Bedaquiline Administration: Administer bedaquiline with a high-fat meal to ensure good bioavailability.
  • Pretomanid Dosing Regimen: The dosing regimen for pretomanid involves daily administration for 26 weeks.
  • CYP3A4 Substrate: Pretomanid acts as a CYP3A4 substrate, meaning it can be metabolized by this enzyme.
  • Linezolid Mechanism: Linezolid operates as a protein synthesis inhibitor, specifically targeting the 50S subunit of bacterial ribosomes.
  • Linezolid Adverse Effect: An adverse effect specifically associated with linezolid is the risk of drug-induced myelosuppression (suppression of bone marrow).
  • Delayed Effect of Bedaquiline: The delayed effect of bedaquiline observed from day 4 onward is attributed to the time required for drug accumulation in the mycobacterial cells.
  • Isoniazid Mode of Action: Isoniazid’s primary mode of action is inhibiting mycolic acid biosynthesis, an essential component of the mycobacterial cell wall.
  • Common Side Effect of Isoniazid: A common side effect of isoniazid treatment is hepatotoxicity.
  • Peripheral Neuropathy Risk: The risk of peripheral neuropathy in patients taking isoniazid increases with higher doses, prolonged treatment, and deficiencies in vitamin B6.
  • Fast Acetylators and Isoniazid: Individuals who are fast acetylators may be at a higher risk during isoniazid treatment because they quickly metabolize the drug.
  • Normal Daily Dose of Isoniazid: The normal daily dose of isoniazid for adults is 300 mg.
  • Rifampicin Action: Rifampicin specifically targets DNA-dependent RNA polymerase, a crucial enzyme for bacterial RNA synthesis, leading to the inhibition of protein synthesis.
  • Slow Acetylators and Isoniazid: For slow acetylators, the suggested daily dose of isoniazid may be reduced to 150 mg to prevent adverse effects.
  • Isoniazid Precaution: A precaution when administering isoniazid is to monitor patients regularly for signs of hepatotoxicity and peripheral neuropathy.
  • N-Acetyltransferase 2 Role: N-Acetyltransferase 2 (NAT2) plays a crucial role in the metabolism of isoniazid. Genetic variations in this enzyme influence the rate at which isoniazid is broken down.
  • Isoniazid Maximum Dose: The maximum dose of isoniazid for adults is 900 mg/day.

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