Antimycobacterials

Question 1

Isoniazid

Answer 1

First Line Antimycobacterial Agent (TB)
MOA:
- Prodrug activated by bacterial enzymes (katG)
- Inhibits synthesis of mycolic acids
–> Preventing mycobacterium cell wall formation

AE:
- Hemolytic anemia (In people with glucose-6-phosphate dehydrogenase deficiency)

Question 1

Rifampicin

Answer 1

First Line Antimycobacterial Agent (TB and Leprosy)
Characteristic:
- Only works on prokaryotic cells

MOA:
- Binds to and inhibits DNA-dependent RNA polymerase
–> Prevents translation of mRNA into proteins

AE:
- Acute interstitial nephritis (rare)
- Orange tinge to saliva, tears, sweat

TB & Leprosy

Question 2

Ethambutol

Answer 2

First Line Antimycobacterial Agent (TB)
Characteristics:
- Only works on mycobacteria

MOA:
- Inhibits arabinosyl transferase
–> Impairs mycobacterial cell wall synthesis

AE:
- Optic neuritis (Red-green colour blindess)
- Peripheral neuropathy
–> Should not be given to those younger than 5 as it is hard to monitor these AE

Question 3

Pyrazinamide

Answer 3

First Line Antimycobacterial Agent (TB)
Characteristics:
- Nicotinamide analog
- Prodrug for Pyrazinoic acid
- Tuberculostearic at acidic pH

MOA:
- Inhibits fatty acid synthase
–> Prevents fatty acid synthesis

AE:
- Gout
- Hepatic Damage

Question 4

Capreomycin

Answer 4

Second Line Antimycobacterial Agent (TB)
Characteristics:
- Peptide antibiotic

MOA:
- Binds 70S ribosomal subunit
–> inhibits protein synthesis

AE:
- Kidney damage
- Auditory nerve damage (Deafness and ataxia)
- Contraindicated with Streptomycin

Question 5

Cycloserine

Answer 5

Second Line Antimycobacterial Agent (TB)
Characteristics:
- Broad spectrum antibiotic

MOA:
- Prevent formation of tripeptide side chains of N-acetylmuramic acid
–> Important building block for peptidoglycan
–> Inhibits bacterial cell wall

Question 6

Streoptomycin

Answer 6

Second Line Antimycobacterial Agent (TB)
MOA:
- Binds irreversibly to 30S subunit to inhibit protein synthesis

Question 7

Bedaquiline

Answer 7

Multi drug resistant TB Agent
Characteristic:
- First-in-class Diarylquinoline agent

MOA:
- Inhibits ATP synthase in mycobacteria

Question 8

Delamanid

Answer 8

Multi drug resistant TB Agent
Characteristic:
- Cell wall active nitro-dihydroimidazooxazoles
- Prodrug activated by mycobacterial nitroreductase
MOA:
- Inhibits synthesis of mycolic acids

Question 9

Dapsone

Answer 9

Antimycobacterial Agent (Leprosy)
Characteristics:
- Related to sulfonamides

MOA:
- Inhibits bacterial folate synthesis

AE:
- Hemolysis of RBC
- Methemoglobinemia,
- Lepra Reactions (Can worsen inflammation)

Question 10

Clofazimine

Answer 10

Antimycobacterial Agent (Leprosy)
Characteristics:
- A dye with proposed action against leprosy bacilli

MOA:
- Involves action on DNA
- May be anti-inflammatory

AE:
- Reddish colour of skin and urine

Question 11

TB Therapy

Answer 11

Initial (2 months)
- Isoniazid, Rifampicin, and Pyrazinamide (possibly Ethambutol)

Continuation (4 months)
- Isoniazid and Rifampicin

Question 12

Leprosy Therapy

Answer 12

Tuberculoid Leprosy (6 months)
- Dapsone, Rifampicin
(Fewer skin lesions)

Lepromatous Leprosy (2 years)
- Dapsone, Rifampicin, Clofazimine
(Wide spread skin lesions)