Anti-Mycobacterials Flashcards

Question

What is the rationale behind the TB treatment strategy?

Answer 1

The key to this treatment strategy is to attack multiple targets at once as TB often has resistance to one single method of attack.

Answer 2

The remaining months are necessary to eradicate the slow-growing fraction of TB.

Answer 3

Streptomycin, along with kanamycin and amikacin, is an aminoglycoside. These drugs target the 30S ribosomal subunit, possibly binding at the interface between the ribosomal subunits. Compromising protein synthesis.

Answer 4

The mycobacteria cell wall does not seem to hamper the entrance of these very hydrophilic antibiotics; this is possibly due to entry via porins/channels.

Answer 5

It specifically inhibits bacterial RNA polymerase (responsible for DNA transcription) by forming a stable drug-enzyme complex.

Answer 6

These drugs work by inhibition of the enzyme’s topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination.

Answer 7

Isoniazid is first activated by KatG into an unstable intermediate which reacts with NAD to give certain compounds. The resulting adduct then binds the NAD(H) recognition site of InhA and this leads to the antimycobacterial effect. InhA is involved in mycolic acid synthesis.

Answer 8

Ethambutol blocks arabinogalactan synthesis by inhibition of an arabinosyl transferase enzyme. Mycolic acids accumulate in the wall, cells become spherical and possibly more permeable to other agents. Its effect on cell wall improves the efficiency of other antibiotics (e.g. clarithromycin) which are usually ineffective on M. tuberculosis. Hence it is given with other agents.

Answer 9

The mechanism of action for pyrazinamide isn’t fully known. It is thought that it works by acidifying the inside of cells by becoming hydrolysed to form a carboxylic acid. This may be done by the action of a specific pyrazinamidase.

Answer 10

Pyrazinamide is effective against dormant bacilli since the death by acidification mechanism does not require much metabolic activity apart from a pyrazinamidase.

Answer 11

Teixobactin is a very promising drug in the fight against TB as it has shown no signs of resistance developing in the bacterium.

Answer 12

Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). This contributes to efficient lysis and killing, by digestion of the cell wall by liberated autolysins.

Answer 13

12-15 million people.

Answer 14

The reason for the continued prevalence of the disease is that there is a massive social stigma surrounding it that can be traced back centuries. Because of this, people are less likely to seek medical advice and let the condition progress.

Answer 15

By air-borne secretions and prolonged close contact with an untreated person suffering from an infectious form of leprosy with an inherent immunological susceptibility to the disease in the exposed person.

Answer 16

Only 10% of patients are infectious of left untreated.

Answer 17

Folded lesions on the face and limbs as well as disfiguration, loss of peripheral nerves, and secondary infection. These obvious symptoms contribute to the social stigma of the disease.

Answer 18

Its mechanism is probably similar to that of the sulphonamides; inhibition of folic acid synthesis. This may lead to selectivity issues.

Answer 19

It inhibits mycobacterial growth and binds preferentially to mycobacterial DNA. It also exerts anti-inflammatory properties in controlling erythema nodosum leprosum reactions.

Answer 20

Clofazimine tends to be deposited predominantly in fatty tissue and in cells of the reticuloendothelial system.

Answer 21

Streptomycin and ethambutol.

Anti-Mycobacterials Flashcards

(46 cards)