Antimycobacterial Drugs Flashcards
The primary reason for drug combination in treating TB is
Delay or prevent the emergene of resistance
For optimum coverage, the initial regimen should include
INH,RIfampin,pyrazinamide, and ethambutol
Fast acetylators may require ___________ doses
Higher
Peripheral neuropathy is caused by _______
INH
Peripheral neuropathy can be prevented by __________
daily dose of 25-50 mg of pyridoxine
INH can inhibit monoamine oxidase type A causing ____________
Tyramine reactions. (dyspnea, flushing, palpiatation, and sweating after ingestion of tyramine containing foods)
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
Rifampin
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
Start treatment with the combination of azithromycin, ethambutol, and rifabutin
________is advisable for all household members and very close contacts of TB patients
INH
Resistance to ethambutol involves mutations in the _______
emb gene
Mechanism of resistance of rifampin
changes in the drug sensitivity og the polymerasse (endoded by the rpo gene)
Resistance to pyrazinamide
mutations in the gene pncA
Once weekly administration of this drug has prophylactic activity against bacteremia caused by the M. avium cimplex in AIDS patients
Azithromycin
Repository form of dapsone used in Leprosy
Acedapsone
Risk factors for multidrug resistant tuberculosis
- 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%
Isoniazid
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
Rifamycins
(Rifampin, rifabutin, rifapentine)
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
Ethambutol
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
Pyrazinamide
,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
Streptomycin
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
SIngle most important drug used in TB
INH
_______commonly cause light chain proteinuria
Rifampin
___equally effective as anti TB and less likely to cause drug interactions than Rifampin
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
_________has kinetics that allow for once-weekly daosisngh and can be used with INH for latent infections
Rifapentine
A rifampin derivative that is not absorbed from the GI tract and has been used in traveler’s diarrhea
Rifaximin
Hyperuricemia can occur when giving this drug
Pyrazinamide
____is a cogener of INH, but cross resistance does not occur. can cause severe GI irritation and adverse neurologic effects
Ethionamide
Inhibits ATP synthase in mycobacteria. It is approved for TB resistant to both isoniazid and rifampin.
Bedaquiline
most active drug for leprosy
Dapsone
MOA of dapsone
Inhibition of folic acid synthesis
a phenazine dye that may interact with DNA, causes GI irritation and skin discorloration
Clofazimine
Prophylaxis is recommend to patientswith CD4 count _________
<50u/L
