3B : ANTI-MYCOBACTERIUM

Question 1

exerts its effects by reversibly inhibiting DNA-dependent RNA polymerase, which
further inhibits bacterial protein synthesis and transcription.

Answer 1

Rifampin

Question 2

a pro-drug that is converted to its active form metabolite by catalase-peroxidase
and exerts its action by further inhibiting the biosynthesis of mycolic acid.

Answer 2

Isoniazid

Question 3

converted to its active form and exerts its effect by inhibiting
trans-translation and possibly coenzyme A synthesis needed for the bacteria to survive.

Answer 3

Pyrazinamide

Question 4

inhibits the enzyme arabinosyltransferases and prevents the biosynthesis of the
mycobacterial cell wall.

Answer 4

Ethambutol

Question 5

binding to the 30S subunit of ribosomes and inhibiting the protein synthesis of the mycobacteria.

Answer 5

Aminoglycosides (Streptomycin, Kanamycin, Amikacin)

Question 6

inhibiting DNA gyrase and topoisomerase IV, further inhibiting DNA synthesis within the bacteria.

Answer 6

Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin)

Question 7

ADMINISTRATION

oral

Answer 7

Rifampin, Isoniazid, Pyrazinamide, and Ethambutol

Fluoroquinolones such as moxifloxacin, gatifloxacin, and levofloxacin

Question 8

ADMINISTRATION
parenteral

Answer 8

Streptomycin is usually administered daily as a single intramuscular injection

Aminoglycosides are usually administered by intravenous infusion or intramuscular
injection

Question 9

Adverse Effects

Rifampin:

Answer 9

• Hepatotoxicity,
• Thrombocytopenia,
• Neutropenia,
• Orange/Red discoloration of bodily
  fluids,
• CYP450 Inducer

Question 10

Adverse Effects

Isoniazid:

Answer 10

• Hepatotoxicity,
• Vitamin B6 deficiency,
• Peripheral Neuropathy

Isoniazid can interfere with the activity of vitamin B6. Vitamin B6 supplementation
is recommended, especially in people with poor nutritional status, to prevent the
development of isoniazid-induced peripheral neuritis (inflamed nerves).

INH metabolites directly attach to and inactivate pyridoxine species. The
combination of isoniazid and pyridoxine form a hydrazone which is excreted in
the urine.

INH inhibits the enzyme pyridoxine phosphokinase; this enzyme is necessary
to activate pyridoxine to pyridoxal 5’ phosphate, the cofactor in many
“pyridoxine-dependent” reactions

Question 11

adverse effect

Pyrazinamide:

Answer 11

• Hepatotoxicity,
• Hyperuricemia,
• Arthralgia

Question 12

ADVERSE EFFECT

Ethambutol:

Answer 12

• Optic neuropathy,
• Hepatotoxicity

Question 13

ADVERSE EFFECT

Aminoglycosides (Streptomycin, Kanamycin, Amikacin):

Answer 13

• Ototoxicity,
• Nephrotoxicity

Question 14

ADVERSE EFFECT

Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin):

Answer 14

• Tendonitis,
• Tendon rupture,
• Arthropathy

Question 15

During pregnancy, all anti-tubercular medications are useful for treatment except for

Answer 15

AMINOGLYCOSIDES.

Aminoglycosides such as streptomycin, amikacin, and kanamycin may
exhibit ototoxic effects on the developing fetus

Question 16

thioamide derivative with antitubercular activity
Used to treat MDR TB

Answer 16

PROTIONAMIDE

Question 17

MOA of protionamide

Answer 17

Forms a covalent adduct with bacterial nicotinamide adenine dinucleotide (NAD),
PTH-NAD, which competitively inhibits 2-trans-enoyl-ACP reductase (inhA), an enzyme
essential for mycolic acid synthesis; results in increased cell wall permeability and decreased
resistance against cell injury eventually leading to cell lysis.

Question 18

ADVERSE EFFECT OF PROTIONAMIDE

Answer 18

• Most commonly associated with nausea and vomiting.
• It may cause depression and hallucinations.
• Rarely, prothionamide will cause jaundice, menstrual disturbances and peripheral neuropathy.

Not recommended for pregnant women as it has been shown to be teratogenic in animal
studies

Question 19

analog of the amino acid D-alanine with broad-spectrum antibiotic activities

Answer 19

CYCLOSERINE

Question 20

an excitatory amino acid and partial agonist at the glycine
binding site of the NMDA receptor in the central nervous system (CNS); binding to the
central NMDA receptor may result in amelioration of neuropathic pain

Answer 20

D-cycloserine

Question 21

a broad spectrum antibiotic used as a second line agent for treatment of drug
resistant tuberculosis, always in combination with other antituberculosis agents.

Answer 21

CYCLOSERINE

Question 22

Symptoms of acute toxicity of cycoloserine generally involve

Answer 22

the CNS and include
* headache,
* vertigo,
* confusion,
* drowsiness,
* hyperirritability,
* paresthesias,
* dysarthria, and
* psychosis.

Paresis, seizure, and coma may occur with large cycloserine overdosages; alcohol ingestion
may increase the risk of seizures.

Question 23

Member of a new class of drugs called the diarylquinolines

Blocks the proton pump for ATP synthase of mycobacteria

Answer 23

BEDAQUILINE

Question 24

Resistance bedaquiline

Answer 24

• The specific part of ATP synthase affected by bedaquiline is subunit c which is
  encoded by the gene atpE. Mutations in atpE can lead to resistance.

Mutations in drug efflux pumps have also been linked to resistance

Question 25

Most common side effects of bedaquiline

Answer 25

include nausea, joint and chest pain, and headache

Question 26

black box warning of bedaquiline

Answer 26

• increased risk of death and arrhythmias, as it may prolong the QT
  interval by blocking the hERG channel

Question 27

considerations in giving bedaquiline

Answer 27

can also cause hepatotoxicity

Should** not be co-administered with other drugs that are strong inducers or inhibitors
of CYP3A4**, the liver enzyme responsible for oxidative metabolism of the drug

Example:

Rifampicin - strong CYP3A4 inducer

Ketoconazole - strong CYP3A4 inhibitor

Approved for use in multidrug-resistant tuberculosis, and the more resistant extensively
drug resistant tuberculosis

Question 28

FREQUENCY OF QT INTERVAL MONITORING AND MANAGEMENT OF QT
INTERVAL PROLONGATION