Anti-TB Pharm

Question 1

most active TB drugs

Answer 1

isoniazid

rifampin

Question 2

benefit of adding pyrazinamide to the 9 month regimen of isoniazid + rifampin

Answer 2

allows duration of therapy to be reduced to 6 months without a drop in efficacy

Question 3

benefit of adding ethambutol (or streptomycin) to 9 month regimen of isoniazid and rifampin

Answer 3

provides additional coverage in case TB strain is resistant to isoniazid or rifampin

Question 4

MOA of isoniazid

Answer 4

inhibits mycolic acid synthesis

Question 5

resistance to isoniazid

Answer 5

• overexpression of inhA
• mutation or deletion in katG gene
• promotor mutations resulting in overexpression of ahpC
• mutations in kasA

Question 6

adverse effects isoniazid

Answer 6

• isoniazid-induced hepatitis

- peripheral neuropathy

Question 7

MOA of rifampin

Answer 7

• inhibits RNA synthesis by binding to the beta subunit of bacterial DNA-dependent RNA polymerase
• bactericidal
• good at penetration and can kill intracellular organisms and those sequestered in abscesses and lung cavities

Question 8

how does rifampin increase metabolism of other drugs

Answer 8

it induces CYP450 isoforms

Question 9

resistance to rifampin

Answer 9

• point mutations in rpoB (gene for beta subunit of RNA polymerase)
• cross resistance to other rifampin derivatives

Question 10

why must rifampin be administered with another anti-TB med

Answer 10

to prevent emergence of drug resistance

Question 11

adverse effects rifampin

Answer 11

• harmless orange color to urine, sweat, tears

- occasionally: rashes, thrombocytopenia, nephritis

Question 12

MOA of ethambutol

Answer 12

inhibition of mycobacterial arabinosyl transferases

Question 13

resistance to ethambutol

Answer 13

mutation resulting in overexpression of emb gene products or within the embB structural gene (overwhelms ethambutol)

Question 14

adverse effects ethambutol

Answer 14

retrobulbar nephritis

- loss of visual acuity and red-green color blindness

Question 15

MOA of pyrazinamide

Answer 15

converted to pyrazinoic acid by mycobacterial pyrazinamidase which then disrupts the mycobacterial cell wall metabolism and transport functions

Question 16

resistance to pyrazinamide

Answer 16

• impaired uptake of pyrazinamide

- mutations in pncA that impair conversion of pyrazinamide to its active form

Question 17

adverse effects pyrazinamide

Answer 17

• hepatotoxicity, nausea, vomiting, drug fever, photosensitivity, hyperuricemia

Question 18

MOA streptomycin

Answer 18

aminoglycoside antibiotic (blocks protein synthesis)

Question 19

adverse effects streptomycin

Answer 19

• ototoxic and nephrotoxic

- vertigo and hearing loss

Question 20

MOA ethionamide

Answer 20

blocks synthesis of mycolic acids similarly to isoniazid

Question 21

resistance ethionamide

Answer 21

(same as isoniazid)

• overexpression of inhA
• mutation or deletion in katG gene
• promotor mutations resulting in overexpression of ahpC
• mutations in kasA

Question 22

adverse effects ethionamide

Answer 22

gastric irritation and neurologic sx

Question 23

MOA capreomycin

Answer 23

peptide protein synthesis inhibitor

Question 24

adverse effects capreomycin

Answer 24

nephrotoxic and ototoxic

- tinnitus, deafness, vestibular disturbances

Question 25

MOA cycloserine

Answer 25

structural analog of D-alanine and incorporates into peptidoglycan pentapeptide which inhibits cell wall synthesis

Question 26

adverse effects cycloserine

Answer 26

peripheral neuropathy and CNS dysfunction (depression and psychoses)
- HA, tremors, convulsions

Question 27

MOA aminosalicylic avid

Answer 27

folate synthesis inhibitor active exclusively against M. tuberculosis

Question 28

adverse effects aminosalicylic acid

Answer 28

• GI (peptic ulceration, hemorrhage)

- hypersensitivity reactions

Question 29

MOA kanamycin/amikacin

Answer 29

aminoglycoside antibiotics (inhibits protein synthesis)

Question 30

when to use amikacin

Answer 30

tx for TB suspected to be caused by streptomycin-resistant or multi-drug resistant strains

Question 31

adverse effects kanamycin/amikacin

Answer 31

ototoxic and nephrotoxic

- vertigo and hearing loss

Question 32

MOA of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin

Answer 32

fluoroquinolone antibiotics (inhibit topoisomerase II and IV)

Question 33

resistance to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin

Answer 33

point mutations in DNA gyrase

Question 34

adverse effects to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin (fluoroquinolone drugs)

Answer 34

• GI: abd discomfort, nausea, vomiting, C. diff
• CNS: HA, dizziness
• achiles tendon rupture
• QT prolongation and torsades de poinets

Question 35

MOA linezolid

Answer 35

oxazolidinone antibiotic (inhibits protein synthesis)

Question 36

resistance to linezolid

Answer 36

point mutations at oxazolidinone binding site or methyltransferases altering oxazolidinone binding to the ribosome

Question 37

adverse effects oxazolidinone drug class (linezolid)

Answer 37

• myelosuppression
• mitochondrial toxicity
• drug-drug interactions

Question 38

MOA rifabutin

Answer 38

• bacterial RNA polymerase inhibitor

Question 39

resistance to rifabutin

Answer 39

point mutations in rpoB (beta subunit for RNA polymerase)

Question 40

adverse effects rifabutin

Answer 40

hepatotoxicity and rash

- also leukopenia, thombotypenia, optic neuritis

Question 41

MOA rifapentine

Answer 41

bacterial RNA polymerase inhibitor

Question 42

resistance to rifapentine

Answer 42

point mutations in rpoB (beta subunit for RNA polymerase)

Question 43

adverse effects rifapentine

Answer 43

hepatotoxicity and rash

Question 44

MOA bedaquiline

Answer 44

inhibits ATP synthase in mycobacteria

Question 45

resistance bedaquiline

Answer 45

upregulation of multi-substrate efflux pump

Question 46

adverse effects bedaquiline

Answer 46

• nausea, arthralgia, HA
• hepatotoxicity and cardiac toxicity
• QT prolongation