Antimycobacterials

Question 1

Rifamycin MOA

Answer 1

Rifampicin and rifabutin.
Bactericidal
Inhibit DNA-dependent RNA polymerase

Question 2

Rifampicin spectrum of activity

Answer 2

Not used for common gram+Ve infections.
Reserved for MRSA, mycobacterial infections, and prophylaxis of meningitis/epiglottis.

Question 3

Rifamycin ADRs

Answer 3

Common- flushing and itching. Orange-red tears, saliva, urine, sweat.

Infrequent- wheeze, allergy, cholestatic jaundice, hepatotoxicity, blood dyscrasia (thrombocytopenia, neutropenia).

Rare- neurological, IV thrombocytopenia

Question 4

Rifampicin allergy

Answer 4

infrequent.
Includes: rash, flu, anaemia, acute renal failure.

If taken irregular/intermittently or if restarting.

Question 5

Rifampicin drug interactions

Answer 5

CYP450.
Reduces levels of warfarin, contraception, theophylline, itraconazole, steroids, opioids, phenytoin, and verapamil.

Rifabutin has less than rifampicin

Question 6

Isoniazid (INH) MOA

Answer 6

Bactericidal against actively dividing M. tuberculosis
Bacteriostatic against resting bacteria
Active against intra and extracellular organisms

Reduce catalase-peroxidase to inhibit synthesis of mycolic acid part of cell wall.

Question 7

INH ADRs

Answer 7

Hepatitis from toxic metabolite (acetyl-hydrazine)
- serum level distribution from ‘fast’ and ‘slow’ acetylation phenotypes

Peripheral neuropathy from vitamin B6 deficiency
INH activates vitamin B6

Question 8

INH interactions

Answer 8

Alcohol + rifampicin + INH = hepatotoxicity risk

Increased carbamazepine and phenytoin

Aluminium salts inhibit INH absorption

Question 9

Pyrazinamide MOA

Answer 9

Bactericidal against M. tuberculosis in acidic pH
Active against bacteria in macrophage

Activity declines over time
pH increases as inflammation decreases

Question 10

Pyrazinamide ADRs

Answer 10

Common- hyperuricaemia, polyarthralgia, nausea

Infrequent- urticaria, itch, dysuria, hepatotoxicity, rash, allergy

Rare- anaemia, thrombocytopenia, photosensitivity, acute gout

Question 11

Pyrazinamide CI and caution

Answer 11

CI- significant liver disease and porphyria

Caution- Gout, renal impairment, diabetes

Question 12

Association of pyrazinamide to hepatotoxicity

Answer 12

Asymptomatic elevation of liver enzymes (fever, anorexia, malaise, liver tenderness, hepatomegaly)

Serious liver disease (clinical jaundice, hepatic necrosis)

Question 13

Ethambutol MOA

Answer 13

Bacteriostatic against mycobacteria

Inhibit RNA synthesis

Synthetic butanol derivative class

Question 14

Ethambutol indications

Answer 14

Mycobacterium tuberculosis
M. avium-intracellulare infection

Question 15

Ethambutol ADRs

Answer 15

Common- optic neuritis

Infrequent- headache,