AntiMycobacterial Drugs

Question 1

Mycobacteria key characeristics-what kind of stain do you use to test for mycobacteria?

Answer 1

Rod shaped, form filaments
Gram stain poorly/not at all
Acid fast stain positive
Generally slow growing

Question 2

Preferred Regiment for the TX of active TB

Answer 2

Initial phase: Daily INH, RIF, PZA, and EMB for 56 dosers (8 weeks)
Continuation phase: Daily INH and RIF for 126 doses (18 weeks) or
Twice weekly INH and RIF for 36 doses (18 weeks)

Question 3

What is the most active drug used in the tx of TB (active and latent)?

Answer 3

Isoniazid-Very safe and very effective

Question 4

Isoniazid MOA

Answer 4

Delivered as prodrug, activated by Kat G and forms a covalent bond w/ at least two proteins in mycolic acid synthesis and impeded their function.

Question 5

Isoniazid resistance

Answer 5

Mutation in Kat G gene

Overexpression of the Inh A protein (mycolic acid synthesis protein)

Question 6

What should be remembered about treating TB w/ isoniazid

Answer 6

Drug resistance is a problem!=>It is essential that at least two active antituberculosis agents always be used to treat active TB to prevent the emergence of drug resistance during therapy.

Question 7

Isoniazid adverse rxns

Answer 7

Hepatitis-risk increases w/ age and alcohol dependence
Peripheral neuropathy- Often observed in people who exceed the standard dose and individuals who slowly metabolize the drug.
-Also seen in pts who are malnourished, alcoholic, diabetic, or suffer from AIDS

Question 8

Rifampin MOA

Answer 8

Inhibits RNA synthesis

Binds to bacterial DNA-dependent RNA polymerase

Question 9

Rifampin Resistance

Answer 9

Point mutations in teh bacterial RNA polymerase gene

Question 10

Rifampin adverse reactions

Answer 10

Harmless red/orange color being imparted into urine, feces, sweat, tears, and saliva
Drug interactions: Induces cytochrome p450=>increases elimation of other drugs, especially antiretroviral drugs=>in HIV pts, substitute w/ Rifabutin

Question 11

Pyrazinamide MOA

Answer 11

Prodrug, inhibits mycolic acid synthesis (we think)

Antimicrobial activity is dependent upon an acidic environment

Question 12

Pyrazinamide resistance

Answer 12

Mutation in the prodrug converting enzyme

Question 13

Pyrazinamide Adverse

Answer 13

Hepatotoxicity

Hyperuricemia=>development of gout

Question 14

Ethambutol MOA

Answer 14

Inhibits arabinosyl transferases=>involved in cell wall synthesis

Question 15

Ethambutol resistance

Answer 15

Point mutations in genes encoding arabinosyl transferases

Always given in combo thearpy

Question 16

Ethambutol Adverse

Answer 16

Retrobulbar neuritis=> impaired visual acuity, red/green color blindness
Hyperuricemia

Question 17

Streptomycin MOA

Answer 17

Interferes w/ bacterial protein synthesis

Question 18

Streptomycin resistance

Answer 18

Point mutations in ribosomal proteins

Question 19

Streptomycin adverse

Answer 19

Ototoxic

Nephrotic

Question 20

Rifabutin use

Answer 20

Same MOA and resistance as rifampin
Greater activity against MAC
Commonly substituted for rifampin in Tx of TB in HIV infected pts.

Question 21

M.avium complex (MAC) Tx

Answer 21

Macrolide antibioitc (clarithromycin or azithromycin)
Rifampin
Ethambutol
+/- Streptomycin

Question 22

Treatment of Leprosy-drugs and tx time span

Answer 22

Dapsone, flofazimine, and rifampin

Therapy last for years

Question 23

Dapsone MOA

Answer 23

Competitive inhibitor of folic acid synthesis

Question 24

Dapsone adverse

Answer 24

Can induce non-hemolytic anemias

Can induce hemolytic anemia in pts w/ G6PD