Antimycobacterial Drugs

Question 1

The primary reason for drug combination in treating TB is

Answer 1

Delay or prevent the emergene of resistance

Question 2

For optimum coverage, the initial regimen should include

Answer 2

INH,RIfampin,pyrazinamide, and ethambutol

Question 3

Fast acetylators may require ___________ doses

Answer 3

Higher

Question 4

Peripheral neuropathy is caused by _______

Answer 4

INH

Question 5

Peripheral neuropathy can be prevented by __________

Answer 5

daily dose of 25-50 mg of pyridoxine

Question 6

INH can inhibit monoamine oxidase type A causing ____________

Answer 6

Tyramine reactions. (dyspnea, flushing, palpiatation, and sweating after ingestion of tyramine containing foods)

Question 7

A patient on TB treatment was advised no to rely on oral contraceptive becasue they may be less effective while she is being treated. The agent most likely to interfere with the action of oral contraceptives

Answer 7

Rifampin

Question 8

A patient with AIDS and a CD4 count of <100 has persistent fever and weight loss associated with invasive pulmonary disease due to M. Avium compelx. Optimal management of this patient is to

Answer 8

Start treatment with the combination of azithromycin, ethambutol, and rifabutin

Question 9

________is advisable for all household members and very close contacts of TB patients

Answer 9

INH

Question 10

Resistance to ethambutol involves mutations in the _______

Answer 10

emb gene

Question 11

Mechanism of resistance of rifampin

Answer 11

changes in the drug sensitivity og the polymerasse (endoded by the rpo gene)

Question 12

Resistance to pyrazinamide

Answer 12

mutations in the gene pncA

Question 13

Once weekly administration of this drug has prophylactic activity against bacteremia caused by the M. avium cimplex in AIDS patients

Answer 13

Azithromycin

Question 14

Repository form of dapsone used in Leprosy

Answer 14

Acedapsone

Question 15

Risk factors for multidrug resistant tuberculosis

Answer 15

• History of previous trearment without rifampin
• Recent immigration from asia and living in a rea if over 4% isoniazid resistance
• Recent immigration from Latin america
• Residence in regions where isoniazid resistance is known to exceed 4%

Question 16

Isoniazid

Answer 16

Reuires bioactivation. Inhibits mycolic acid synthesis, Resistance via expression of katG and inhA genes

Bactericidal, Primary drug for LTBI and a primary drug use in combinations

Oral and Iv forms. Heaptic clearance (fast and slow acetylators). Inhibits metabolism of carbamazepine, phenytoin, and warfarin

SE: hepatotoxicity, perpheral neuropathy (use pyridcoine). hemolysis in G6PD deficiency

Question 17

Rifamycins

(Rifampin, rifabutin, rifapentine)

Answer 17

Inhibit DNA-dependenr RNA polymerase. resistance emerges rapidly when drug is used alone

Bactericidal. Rifampin is an optional drug for LTBI. a primary drug used in combinations for active TB

Tifampin (Oral, IV). Others oral. Enterohepatic cycling with some metabolism. Induced formation of P450 by rifampin leads to decreased efficacy of many drugs (rifabutin less). Rifapentine once a week dosing for LTBI or select TB cases

SE: Rash, nephritis, cholestasis, thrombocytopenia. Flu-like syndrome with intermittent dosing

Question 18

Ethambutol

Answer 18

Inhibits formation of arabinoglycan, a component of mycobacterial cell wall. Resistance emerges rapidly if drug is used alone

Bacteriostatic, component of many drug combination regimens for active TB

Oral. Renal elimination with large fraction unchanged. Reduce dose in renal dysfunction

SE: DOse dependent visual disturbances. Reversible on discontinuance. HEadache, confusion, hyperuricemia, and peripheral neuritis

Question 19

Pyrazinamide

Answer 19

,Uncertain, but requires bioactivation via hydrolytic enzymes to form pyrazolic acid (active)

Bacteriostatic. Component of many drug combination regimens for active TB

Oral. Both hepatic and renal elimination (reduce dose in dysfunction)

SE: polyarthralgia (40% incidence), hyperuricemia, myalgia, macupapular rash, porphyria and photosensitivity. Avoid in pregnancy

Question 20

Streptomycin

Answer 20

Binds to 30s ribosomal protein S12 inhibiting protein synthesis

Bactericidal. USed in TB when injectible drug is needed or in treatments of drug-resistant strains

Parenteral. renal elimination.

SE: ototoxicity, nephrotoxicity

Question 21

SIngle most important drug used in TB

Answer 21

INH

Question 22

_______commonly cause light chain proteinuria

Answer 22

Rifampin

Question 23

___equally effective as anti TB and less likely to cause drug interactions than Rifampin

Answer 23

Rifabutin

• Preferred over rifampin in the treatment of tuberculosis or other mycobacterial infections in AIDS especially those treated with cytochrome p450 substrates including protease inhibitors or efavirenz

Question 24

_________has kinetics that allow for once-weekly daosisngh and can be used with INH for latent infections

Answer 24

Rifapentine

Question 25

A rifampin derivative that is not absorbed from the GI tract and has been used in traveler’s diarrhea

Answer 25

Rifaximin

Question 26

Hyperuricemia can occur when giving this drug

Answer 26

Pyrazinamide

Question 27

____is a cogener of INH, but cross resistance does not occur. can cause severe GI irritation and adverse neurologic effects

Answer 27

Ethionamide

Question 28

Inhibits ATP synthase in mycobacteria. It is approved for TB resistant to both isoniazid and rifampin.

Answer 28

Bedaquiline

Question 29

most active drug for leprosy

Answer 29

Dapsone

Question 30

MOA of dapsone

Answer 30

Inhibition of folic acid synthesis

Question 31

a phenazine dye that may interact with DNA, causes GI irritation and skin discorloration

Answer 31

Clofazimine

Question 32

Prophylaxis is recommend to patientswith CD4 count _________

Answer 32

<50u/L