FB - Anti-tuberculosis agents

Question 1

What are the first line drugs against tuberculosis?

Answer 1

(RIPES)

Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin

Question 2

What is the mechanism of action of rifampicin?

Answer 2

Rifampicin inhibits gene transcription of mycobacteria by blocking the DNA-dependent RNA polymerase, which prevents the bacillus from synthesizing messenger RNA and protein, causing cell death.

Question 3

State 2 clinical indications for rifampicin

Answer 3

1. Latent / Active tuberculosis

2. Leprosy, against Mycobacterium leprae

Question 4

Which organism causes tuberculosis?

Answer 4

Mycobacterium tuberculosis

Question 5

Which of the 4 standard first line anti-tuberculosis drugs are safe for use in patients with kidney failure?

Answer 5

Rifampicin and Isoniazid

Question 6

Name 3 adverse effects associated with rifampicin

Answer 6

1. Hepatitis
2. Cutaneous reactions
3. Gastrointestinal symptoms

Question 7

What is the mechanism of action of isoniazid?

Answer 7

Isoniazid is activated by the catalase-peroxidase enzyme of M. tuberculosis. The activation of isoniazid produces oxygen-derived free radicals that can inhibit the formation of mycolic acids of the bacterial cell wall, cause DNA damage and, subsequently, the death of the bacillus.

Question 8

Which enzyme is involved in the metabolism of isoniazid, and presents with wide variation in activity in the community due to genetic polymorphisms?

Answer 8

N-acetyl transferase (rapid acetylator vs slow acetylator phenotypes are found in the population due to the genetic polymorphism

Question 9

State 2 adverse effects related to isoniazid

Answer 9

State 2 adverse effects related to isoniazid 1. Peripheral Neuropathy
2. Hepatitis

Question 10

Patients on isoniazid are often co-administered _________ to help overcome ________ deficiency to avoid peripheral ________ .

Answer 10

pyridoxine, vitamin B6, neuropathy

Question 11

What food – food interactions must patients taking isoniazid be aware for?

Answer 11

They should avoid food rich in tyramine and histamine (certain types of fish, cheese and red wine).

Question 12

What is the mechanism of action of pyrazinamide?

Answer 12

Pyrazinamide is converted to its active form, pyrazinoic acid, by the microbial enzymes. The accumulation of pyrazinoic acid decreases the intracellular pH to levels that cause the inactivation of critical pathways necessary for the survival of the bacteria.

Question 13

Which of the first line anti-tuberculosis drugs is highly effective against the persistent bacilli

Answer 13

Pyrazinamide

Question 14

Which of the 4 standard first line anti-tuberculosis drugs must be avoided or used with caution if the patient suffers from liver disease?

Answer 14

(RIP)

Rifampicin
Isoniazid
Pyrazinamide

Question 15

Which of the 4 standard first line anti-tuberculosis drugs (R.I.P.E) is/are highly associated with causing gout like symptoms?

Answer 15

1. Pyrazinamide (More common with pyrazinamide then ethambutol)
2. Ethambutol

Question 16

Which of the 4 standard first line anti-tuberculosis drugs must be avoided or used with caution if the patient suffers from kidney impairment?

Answer 16

1. Pyrazinamide

2. Ethambutol

Question 17

What is the mechanism of action ethambutol?

Answer 17

Ethambutol inhibits the arabinosyltransferase enzyme and interferes with the polymerization of arabinose into arabinogalactan, the principal polysaccharide on the mycobacterial cell wall.

Question 18

Which of the 4 standard first line anti-tuberculosis drugs (R.I.P.E) is/are highly associated with causing visual toxicity?

Answer 18

Ethambutol

Question 19

Which class of antibiotics does streptomycin belong to?

Answer 19

Aminoglycoside

Question 20

How is streptomycin administered?

Answer 20

Intramuscular injection

Question 21

In which groups of individuals would physicians have a high index of suspicion for multi drug-resistant tuberculosis?

Answer 21

Individuals

1. who were previously treated for TB,
2. who have failed TB treatment,
3. who are known contacts of patients with MDR-TB, or
4. who come from countries with high prevalence of drug resistant tuberculosis