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?
Correct Answer
A. Mycolic acids
Explanation
Isoniazid=Isonicotinic acid hydrazide (INH)
Bactericidal
Narrow-spectrum
Mechanism of action:
KatG gene in mycobacteria encodes catalase-peroxidase in mycobacteria. Catalase-peroxidase converts INH to active form.
activated form of INH inactivates the enzymes involved in mycolic acid synthesis – enoyl-acyl carrrier protein(ACP) reductase (encoded by InhA) and beta-ketoacyl-ACP synthase (encoded by KasA), resulting in the inhibition of mycolic acid sysnthesis, and subsequently, inhibition of call wall synthesis.
2.
Which of the following antimycobacterial drugs is inactivated by hepatic acetylation, the rate of which depends on genetic background?
Correct Answer
D. Isoniazid
3.
High level of resistance of tubercle bacilli to isoniazid involves a decrease in the activity of which of the following enzymes?
Correct Answer
A. Catalase-peroxidase
Explanation
Resistance to Isoniazid:
Mediated primarily by mutations of the KatG gene, resulting in the loss of the catalase-peroxidase enzyme that is required for the activation of isoniazid
-Overexpression of InhA
Isoniazid=Isonicotinic acid hydrazide (INH)
Bactericidal
Narrow-spectrum
Mechanism of action:
KatG gene in mycobacteria encodes catalase-peroxidase in mycobacteria. Catalase-peroxidase converts INH to active form.
activated form of INH inactivates the enzymes involved in mycolic acid synthesis – enoyl-acyl carrrier protein(ACP) reductase (encoded by InhA) and beta-ketoacyl-ACP synthase (encoded by KasA), resulting in the inhibition of mycolic acid sysnthesis, and subsequently, inhibition of call wall synthesis.
4.
A 56-year-old man complained of tingling sensation in his limbs and that his arms sometimes felt 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 symptoms?
Correct Answer
B. Pyridoxine
Explanation
Isoniazid=Isonicotinic acid hydrazide (INH)
Bactericidal
Narrow-spectrum
Mechanism of action:
KatG gene in mycobacteria encodes catalase-peroxidase in mycobacteria. Catalase-peroxidase converts INH to active form.
activated form of INH inactivates the enzymes involved in mycolic acid synthesis – enoyl-acyl carrrier protein(ACP) reductase (encoded by InhA) and beta-ketoacyl-ACP synthase (encoded by KasA), resulting in the inhibition of mycolic acid sysnthesis, and subsequently, inhibition of call wall synthesis.
5.
The mechanism of action of rifampin includes an inhibition of which of the following enzymes?
Correct Answer
A. DNA dependent RNA-polymerase
Explanation
Rifamycin derivatives (Rifampin, Rifapentin, Rifabutin)
Bactericidal; penetrates most tissues and into phagocytes
Broad spectrum antibiotic
G(+), G(-), Acid-fast bacilli (TB, Leprosy)
Mechanism of action :
Inhibits transcription by binding to beta subunit of DNA-dependent RNA polymerase
6.
Which of the following is the most likely mechanism of resistance of M.tuberculosis to rifampin?
Correct Answer
C. Changes in bacterial RNA polymerase
Explanation
Resistance:
By decreased affinity of RNA polymerase for rifampin
always combined with other drugs for the treatment of active infection
7.
A 63-year-old man presented to the hospital complaining of anorexia, nausea and vomiting and abdominal discomfort. He also had pain on motion and stiffness in several joints. He was recently diagnosed with renal tuberculosis and started on a 4 drug combination regimen 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 symptoms and signs?
Correct Answer
B. Pyrazinamide
Explanation
Therapeutic Uses:
Pyrazinamide is an important component of short-course (6-month) multiple-drug therapy of tuberculosis.
It is administered together with INH and Rifampin for the first 2 months of treatment of active tuberculosis.
Combination of pyrazinamide with these antimycobacterial drugs made it possible to reduce the treatment duration for active tuberculosis to 6 months.
Adverse effects:
Hepatitis
Hyperuricemia, Gout
Arthralgia
Hematologic toxicity
Nicotinamide derivative
Bactericidal
Mechanism of action:
Pyrazinamide is active at acidic pH. The drug is taken up by the macrophages and exerts its activity against mycobacteria residing within the acidic environment of lysosomes.
Pyrazinamide is converted by mycobacterial pyrazinamidase to its active form- pyrazinoic acid that inhibits the growth of M. tuberculosis.
8.
A 7-year-old girl was admitted to the hospital with high fever and nuchal rigidity and was later diagnosed with meningococcal meningitis. Which of the following drugs was most likely given prophylactically to her 10 year old sister?
Correct Answer
E. Rifampin
Explanation
Rifampin as prophylactic agent:
As prophylactic agent to prevent several infections
As an alternative to INH, for the prevention of active TB in patients with latent TB, especially when resistance to INH is known or suspected.
To prevent meningococcal disease in those who have had close contact with a Neisseria meningitidis-infected person, and to eradicate carrier state
Given to individuals who came in close contact with patients with Haemophilus influenzae type b (Hib) infection
9.
A 67-year-old man, recently diagnosed with pulmonary tuberculosis, started a treatment with antitubercular drugs. The man has been suffering from atrial fibrillation, and he is presently taking warfarin as one his various drugs. At this point, which of the following changes in the therapeutic regimen of the patient would be appropriate?
Correct Answer
A. To increase the dose of warfarin
Explanation
The correct answer is to increase the dose of warfarin. Warfarin is a blood thinner that is commonly used to prevent blood clots in patients with atrial fibrillation. However, rifampin, one of the antitubercular drugs, can increase the metabolism of warfarin, leading to a decrease in its effectiveness. Therefore, increasing the dose of warfarin would be appropriate to maintain its therapeutic effect in the presence of rifampin.
10.
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 3 drug combination regimen for two months. Which of the following drugs has most likely caused these adverse effects?
Correct Answer
D. Ethambutol
Explanation
Ethambutol:
Bacteriostatic
Mechanism of action:
Ethambutol inhibits the synthesis of arabinogalactan (a component of cell wall) by inhibiting the enzyme arabinosyl transferase (encoded by embCAB)
Deters resistance to bactericidal drugs in TB therapy
Tuberculosis
Ethambutol is given together with other antitubercular drugs - INH, Rifampin, and Pyrazinamide. It helps in preventing the development of resistance where resistance is suspected
M. avium-intracellulare (MAC)
Ethambutol: Adverse effects:
*****Optic neuritis: decreased visual acuity, color blindness (red and green) *****
Peripheral neuropathy
Hyperuricemia
Hepatitis
Thrombocytopenia
11.
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?
Correct Answer
E. To delay the emergence of drug resistance
Explanation
Ethambutol was added to the therapeutic regimen to delay the emergence of drug resistance. Ethambutol is known to have a bacteriostatic effect on Mycobacterium tuberculosis, the bacteria that causes tuberculosis. By adding ethambutol to the treatment, it helps to prevent the development of resistance to the other drugs in the regimen, such as isoniazid, rifampin, and pyrazinamide. This is important because drug resistance can significantly impact the effectiveness of treatment and lead to treatment failure. Therefore, adding ethambutol helps to maintain the efficacy of the overall treatment regimen.
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?
Correct Answer
D. Azithromycin
Explanation
Mycobacterium avium-intracellulare complex (MAC) M. avium-intracellulare infections are seen most frequently in immunocompromised patients (e.g., those with AIDS) and often take the form of pulmonary disease, lymphadenitis, or bacteremia. In immunocompetent persons with chronic bronchitis or emphysema, exposure to M. avium-intracellulare can also result in pulmonary infections.
13.
A 48-year-old man presented to the emergency room with the symptoms of acute gouty arthritis. He was diagnosed with gout a year before and had been taking medications for the chronic control of the disease. He is also on treatment for hypertension. Recently, one and half month ago, he was diagnosed with pulmonary tuberculosis and was started on antitubercular therapy. Which of the following drugs had most likely aggravated his gout?
Correct Answer
F. Pyrazinamide
Explanation
Therapeutic Uses:
Pyrazinamide is an important component of short-course (6-month) multiple-drug therapy of tuberculosis.
It is administered together with INH and Rifampin for the first 2 months of treatment of active tuberculosis.
Combination of pyrazinamide with these antimycobacterial drugs made it possible to reduce the treatment duration for active tuberculosis to 6 months.
Adverse effects:
Hepatitis
Hyperuricemia, Gout
Arthralgia
Hematologic toxicity