This document discusses the anti-tuberculosis drug ethionamide. It is a second-line drug that is an analogue of isonicotinamide but contains sulfur instead of oxygen. It is less active in vitro but more active in vivo due to increased lipophilicity from its ethyl group. Its mechanism of action involves conversion to its active metabolite ethionamide sulfoxide via oxidation, which then inactivates the inhA enoyl reductase enzyme. Less than 1% is excreted unchanged in urine with the rest excreted as metabolites.

1. Ethionamide
• A 2nd line anti TB agent, analogue of
isonicotinamide but it is di-substituted
and contains S in place of O
• It contains ethyl group at position 2

2. • In vitro it is less active but in vivo more active
because of increased lipocity due to C2H5
• Mechanism of action is similar to INH
• Its active metabolite is ethionamide sulfoxide

3. Mechanism of action
• Ethionamide upon oxidation with catalase-
peroxidase is converted to an active acylating
agent, ethionamide sulfoxide, which inturn
inactivate inhA enoyal reductase. It acylates
cystine No. 243 in inhA protein

4. Mechanism of action
Ethionamide sulfoxide
Ethionamide

5. Metabolism
• Less than 1% of the drug is excreted unchanged
in urine. Rest of the drug is excreted as one of the
following metabolites, which are given as follows:

6. Cycloserine
• Analogue of amino acid serine
and it exists in cyclic form- a five
member ring containing O and N at
an adjacent positions,
• Also called Isoxazolidine or oxazolidine
• Obtained naturally as d-isomer
• Contains Keto group at position 3 and NH2 at
position 4, which is in front
• d-isomer is more active

7. • It is 2nd line anti TB drug first isolated from
Streptomyces orchidaceus, but now being
synthesized in laboratory
• It causes CNS toxicity
• Bacteria become resistant after sometime
• It acts on cell wall of bacteria and is not
selective against MT because all bacteria
contain peptidoglycan

8. • It acts on normal peptidoglycan portion of cell
wall rather than acting on outer layer of
mycolic acid
• It inhibits alanine resemase and alanine ligase
• Alanine resemase converts L-isomer of alanine
to d-isomer. Because only d-form can be
incorporated into cell wall. Alanine is present
in levo form, hence need to be converted to d-
form
• Lygase is necessary for attachment of two
alanine units

10. Synthesis

11. • Readily absorbed after oral administration and
is widely distributed including CNS
• It binds to neuronal N-methyl, D-aspaartate
receptor and effects the synthesis and
metabolism of aminobutyric acid leading to
serious CNS effects