Aminoglycosides and Antituberculosis Drugs

Question 1

Aminoglycosides

Answer 1

Primarily used in infections caused by aerobic gram- bacteria and in sepsis.
Used with a cell wall-active agent, such as penicillin or vancomycin
Given IM or IV

Question 2

Aminoglycosides Side effects

Answer 2

Ototoxicity - Largely irreversible
Tobramycin affects vestibular and cochlear sensory cells, but netilmycin is less ototoxic)
Nephrotoxicity (8-26%) - is largely reversible

Question 3

Aminoglycosides Drug Resistance

Answer 3

Inactivation by microbial enzymes
Failure of drug transport
Altered drug target in the bacterial ribosome

Question 4

Streptomycin

Answer 4

First aminoglycoside discovered
Rarely used today
Bacterial endocarditis
Plague
Tuberculosis

Question 5

Neomycin

Answer 5

Topically for infections of the skin and mucous membranes

Question 6

Kanamycin

Answer 6

Second-line drug for treating tuberculosis

Question 7

Gentamycin and Tobramycin

Answer 7

Gentamycin most commonly used aminoglycoside, while tobramycin is preferred member of the group.
Pneumonia, meningitis, endocarditis, sepsis, UTI

Question 8

Tobramycin

Answer 8

Used commonly with antipseudomonal penicillin for pseudomnas infection

Question 9

Amikacin and Netilmicin

Answer 9

Semisynthetic products
Good for infections resistant to gentamycin and tobramycin
Effective against mycobacterium tuberculosis
Most expensive aminoglycoside

Question 10

Mycobacterium Tuberculosis

Answer 10

Microorganism that causes tuberculosis
Primary Drugs: Isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide
Secondary Drugs: Ethionamide, p-aminosalicylic acid, cycloserine, capreomycin, kanamycin, and amikacin

Question 11

Isoniazid

Answer 11

It inhibits synthesis of mycolic acids important in cell wall of TB.
Cross-resistance with other antituberculostatic drugs does not occur
Acetylation of drug leads to inactivation.
First choice drug

Question 12

Rifampin

Answer 12

Effective against most gram+ bacteria as well as many gram - species, including TB.
Inhibits RNA synthesis. Binds to and inhibits DNA-dependent RNA polymerase in prokaryotic cells.
Drug resistance develops rapidly when rifampin used alone.
Combined with isoniazid very effective in TB treatment.

Question 13

Ethambutol

Answer 13

Inhibits mycobacterial arabinosyl transferases involved in polymerization reaction of arabinoglycan

Question 14

Streptomycin

Answer 14

First drug available for treatment of Tb, but now less commonly used due to increasing resistance.

Question 15

Pyrazinamide

Answer 15

Inhibits fatty acid synthesis in mycolic acid synthesis pathway.
Resistance rapidly developed when used alone.

Question 16

Antituberculosis drugs

Answer 16

First phase: 2 months of 3 drugs: isoniazid, rifampin, pyrazinamide.
Second Phase: 4 months of 2 drugs: isoniazid and rifampin
Longer treatment needed in some cases