Fight Tuberculosis - Quiz about Antitubercular Drugs

1. A 31-year-old homosexual HIV-positive man was found to have latent tuberculosis. A treatment with isoniazid was started. The antibacterial effect of this drug is most likely mediated by the inhibition of the synthesis of which of the following molecules?

Mycolic acids

Peptidoglycan

Arabinogalactan

Topoisomerase II

DNA-dependent RNA polymerase

Answer: A
Isoniazid (INH) inhibits the synthesis of mycolic acid that is a specific constituent of mycobacterial cell wall. It has a narrow-spectrum of activity. It is not effective against all mycobacteria. Mycobacterium leprae and Mycobacterium avium-intracellulare complex are not sensitive to INH.

Explanation

Answer: A
Isoniazid (INH) inhibits the synthesis of mycolic acid that is a specific constituent of mycobacterial cell wall. It has a narrow-spectrum of activity. It is not effective against all mycobacteria. Mycobacterium leprae and Mycobacterium avium-intracellulare complex are not sensitive to INH.

2. Which of the following is the most likely mechanism of resistance of M. tuberculosis to rifampin?

Loss of mycolic acid

Altered bacterial topoisomerase II

Altered bacterial RNA polymerase

Altered bacterial peptidyl-transferase

Increased bacterial acetylation of the drug

Answer: C
Resistance to rifampin results from mutation in the gene that codes for the beta subunit of RNA polymerase. This mutation prevents binding of rifampin to the enzyme. A, B, D, E) These enzymes are not involved in the bacterial resistance to rifampin.

Explanation

Answer: C
Resistance to rifampin results from mutation in the gene that codes for the beta subunit of RNA polymerase. This mutation prevents binding of rifampin to the enzyme. A, B, D, E) These enzymes are not involved in the bacterial resistance to rifampin.

3. A 56-year-old man reports tingling sensation in his limbs and that his arms sometimes feel heavy. He was recently diagnosed with pulmonary tuberculosis and has been receiving isoniazid, rifampin, pyrazinamide and ethambutol for two months. Which of the following drugs would be most appropriate to treat his current symptoms?

Folic acid

Pyridoxine

Cyanocobalamin

Vitamic C

Folinic acid

Answer: B
The patient is most likely suffering from isoniazid-induced peripheral neuropathy, and adverse effect of the drug that can affect as many as 20% of patients at risk, like diabetics and alcoholics. Administration of pyridoxine can correct most symptoms of isoniazid-induced neuropathy, both central and peripheral.

Explanation

Answer: B
The patient is most likely suffering from isoniazid-induced peripheral neuropathy, and adverse effect of the drug that can affect as many as 20% of patients at risk, like diabetics and alcoholics. Administration of pyridoxine can correct most symptoms of isoniazid-induced neuropathy, both central and peripheral.

4. A 45-year-old woman complained of blurred vision and inability to distinguish green objects from red objects. The woman, recently diagnosed with cavitary pulmonary tuberculosis, has been receiving a 4 drug combination regimen for two months. Which of the following drugs has most likely caused these adverse effects?

Isoniazid

Pyrazinamide

Rifampin

Ethambutol

Streptomycin

Answer: D
The symptoms and signs of the patient are most likely due to ethambutol-induced optic neuritis, a serious adverse effect of the drug that is dose- and duration-related. Because of this, periodic visual acuity testing is desirable during ethambutol therapy.

Explanation

Answer: D
The symptoms and signs of the patient are most likely due to ethambutol-induced optic neuritis, a serious adverse effect of the drug that is dose- and duration-related. Because of this, periodic visual acuity testing is desirable during ethambutol therapy.

5. The mechanism of action of rifampin includes an inhibition of which of the following enzymes?

DNA dependent RNA-polymerase

Arabinosyl transferase

Transpeptidase

Topoisomerase II

RNA-dependent DNA-polymerase

Answer: A
Rifampin inhibits DNA dependent RNA-polymerase in mycobacteria and other sensitive microorganisms, by binding strongly to the beta-subunit of this enzyme. This leads to suppression of RNA synthesis. The ultimate effect is bactericidal.
B) This enzyme would be inhibited by ethambutol.
C) This enzyme would be inhibited by beta-lactam antibiotics.
D) This enzyme would be inhibited by fluoroquinolones.
E) This enzyme would be inhibited by reverse transcriptase inhibitors

Explanation

Answer: A
Rifampin inhibits DNA dependent RNA-polymerase in mycobacteria and other sensitive microorganisms, by binding strongly to the beta-subunit of this enzyme. This leads to suppression of RNA synthesis. The ultimate effect is bactericidal.
B) This enzyme would be inhibited by ethambutol.
C) This enzyme would be inhibited by beta-lactam antibiotics.
D) This enzyme would be inhibited by fluoroquinolones.
E) This enzyme would be inhibited by reverse transcriptase inhibitors

6. A 63-year-old man presented to the hospital complaining of abdominal pain, and pain and stiffness in several joints. He was recently diagnosed with renal tuberculosis and started on a regimen of 4 antitubercular drugs one month ago. Lab results showed raised serum uric acid of 13 mg /dl. Which of the following drugs has most likely caused the patient's current symptoms?

Rifampin

Pyrazinamide

Isoniazid

Streptomycin

Azithromycin

Answer: B
The gastrointestinal symptoms together with the joint pain and hyperuricemia strongly indicate that pyrazinamide is the drug that caused these adverse effects. Hepatotoxicity is the major limiting adverse effect of pyrazinamide and is dose-related. Gouty arthritis and arthralgia is also common and dose-related. Hyperuricemia is likely due to inhibition of uric acid secretion in the renal tubules. A) Rifampin can causes hepatitis, more so in combination with isoniazid. However, it does not cause hyperuricemia. C, D, E) These drugs do not cause hyperuricemia.

Explanation

Answer: B
The gastrointestinal symptoms together with the joint pain and hyperuricemia strongly indicate that pyrazinamide is the drug that caused these adverse effects. Hepatotoxicity is the major limiting adverse effect of pyrazinamide and is dose-related. Gouty arthritis and arthralgia is also common and dose-related. Hyperuricemia is likely due to inhibition of uric acid secretion in the renal tubules. A) Rifampin can causes hepatitis, more so in combination with isoniazid. However, it does not cause hyperuricemia. C, D, E) These drugs do not cause hyperuricemia.

7. Which of the following antimycobacterial drugs is inactivated by hepatic acetylation, the rate of which depends on genetic background?

Streptomycin

Ethambutol

Rifampin

Isoniazid

Pyrazinamide

Answer: D
Isoniazid is metabolized by hepatic acetylation that shows genetic polymorphism. Patients may be: a) fast acetylators (mainly in Inuits and Japanese). b) slow acetylators (mainly in most Scandinavians, Jews and north African Caucasians). Fast acetylators require higher dosage than slow acetylators to obtain equivalent therapeutic effects. A, B, C, E) These drugs are not metabolized by acetylation.

Explanation

Answer: D
Isoniazid is metabolized by hepatic acetylation that shows genetic polymorphism. Patients may be: a) fast acetylators (mainly in Inuits and Japanese). b) slow acetylators (mainly in most Scandinavians, Jews and north African Caucasians). Fast acetylators require higher dosage than slow acetylators to obtain equivalent therapeutic effects. A, B, C, E) These drugs are not metabolized by acetylation.

8. A 37-year-old homosexual man with AIDS was recently diagnosed with pulmonary tuberculosis and a treatment with isoniazid, rifampin, pyrazinamide and ethambutol was started. Which of the following statements best explains why ethambutol was added to the therapeutic regimen?

To enhance the antibacterial activity of pyrazinamide

To provide antibacterial activity against atypical mycobacteria

To prevent the neurotoxic effects of isoniazid

To prevent Pneumocystis carinii pneumonia

To delay the emergence of drug resistance

Answer: E
The main reason for the use of any drug combination in the therapy of tuberculosis is to delay the emergence of resistance. In the case of ethambutol this is by far the primary reason, since the drug has only weak bacteriostatic activity against M. Tuberculosis and so cannot add significant antibacterial effect to a given therapeutic regimen.

Explanation

Answer: E
The main reason for the use of any drug combination in the therapy of tuberculosis is to delay the emergence of resistance. In the case of ethambutol this is by far the primary reason, since the drug has only weak bacteriostatic activity against M. Tuberculosis and so cannot add significant antibacterial effect to a given therapeutic regimen.

9. High level of resistance of tubercle bacilli to isoniazid involves a decrease in the activity of which of the following enzymes?

Catalase-peroxidase

DNA-dependent RNA polymerase

Topoisomerase II

Acetyltransferase

Transpeptidase

Answer: A
Isoniazid is in fact a prodrug that must be converted into the active compound by mycobacterial catalase-peroxidase. Resistance is often associated with the deletion of the KatG gene that codes for the synthesis of catalase. In this way activation of the prodrug cannot occur. B, C, D, E) These enzymes are not involved in the mechanism of resistance of mycobacteria to isoniazid.

Explanation

Answer: A
Isoniazid is in fact a prodrug that must be converted into the active compound by mycobacterial catalase-peroxidase. Resistance is often associated with the deletion of the KatG gene that codes for the synthesis of catalase. In this way activation of the prodrug cannot occur. B, C, D, E) These enzymes are not involved in the mechanism of resistance of mycobacteria to isoniazid.

10. Q. 9 A 67-year-old man, recently diagnosed with pulmonary tuberculosis, is started on treatment with rifampin. The man has been suffering from atrial fibrillation, and he is presently taking warfarin as one of his drugs. At this point, which of the following changes in the therapeutic regimen of the patient would be most appropriate?

To increase the dose of warfarin

To reduce the dose of isoniazid

To increase the dose of rifampin

To stop pyrazinamide

Answer: A Rifampin is a strong inducer of the hepatic CYP450 system and can increase the metabolism of many drugs including oral contraceptives, antiepilectic drugs, protease inhibitors, theophylline and warfarin. Therefore the dose of warfarin should be increased to maintain an appropriate anticoagulant effect.

Explanation

Answer: A Rifampin is a strong inducer of the hepatic CYP450 system and can increase the metabolism of many drugs including oral contraceptives, antiepilectic drugs, protease inhibitors, theophylline and warfarin. Therefore the dose of warfarin should be increased to maintain an appropriate anticoagulant effect.

11. A 7-year-old girl is admitted to the hospital with high fever and nuchal rigidity, later diagnosed with meningococcal meningitis. Which of the following drugs would most likely be given prophylactically to her 10 year old sister?

Amikacin

Piperacillin

Isoniazid

Nafcillin

Rifampin

Answer: E
Rifampin is the drug of first choice for chemoprophylaxis of close contacts of patients with meningococcal meningitis. The potential for a close contact to become infected with N. Meningitidis is much greater than for the total population. The drug should be administered as soon as possible since the risk of secondary disease is greatest within two to five days after exposure to index case. Other drugs used for chemoprophylaxis include ceftriaxone and ciprofloxacin. A, B, C, D) These antibiotics are not active against N. Meningitidis.

Explanation

Answer: E
Rifampin is the drug of first choice for chemoprophylaxis of close contacts of patients with meningococcal meningitis. The potential for a close contact to become infected with N. Meningitidis is much greater than for the total population. The drug should be administered as soon as possible since the risk of secondary disease is greatest within two to five days after exposure to index case. Other drugs used for chemoprophylaxis include ceftriaxone and ciprofloxacin. A, B, C, D) These antibiotics are not active against N. Meningitidis.

12. A 32-year-old woman, who was HIV positive, presented with fever, profuse night sweats, poor appetite and a 20-pound weight loss over the past 3 months. Physical examination revealed a cachectic female with a prominent oral thrust and mild splenomegaly. Her CD4+ lymphocyte count was 45 cells/mm and a DNA probe test confirmed the diagnosis of Mycobacterium Avium complex infection. An appropriate multidrug regimen for this patient would include which of the following drugs?

Ceftriaxone

Doxycycline

Metronidazole

Azithromycin

Vancomycin

Answer: D
Mycobacterium Avium-intracellulare complex (MAC) infection is common in AIDS patients and the risk of developing the infection is the highest when the CD4+ lymphocyte count is

Explanation

Answer: D
Mycobacterium Avium-intracellulare complex (MAC) infection is common in AIDS patients and the risk of developing the infection is the highest when the CD4+ lymphocyte count is

Fight Tuberculosis - Quiz About Antitubercular Drugs