C.2. Antimycobacterial drugs Flashcards
list the 1st line antimycobacterial agents
'RIPE' Rifampin Isoniazid (INH) Pyrazinamide Ethambutol
list the 2nd line antimycobacterial agents
streptomycin Amikacin Kanamycin Cycloserine Ciprofloxacin Ofloxacin linezolid
what is the MoA of Isoniazid?
inhibits synthesis of mycolic acid
bactericidal effect
what is the mechanism of resistance of Isoniazid?
deletions in katG gene
what is the most important drug used in TB treatment?
Isoniazid
what are the indications for TB prophylaxis (3)?
- TB exposure in young children, TST negative
- TST conversion in the past 2 years
- TST reactors with high risk (diabetes, HIV positive, immunosuppressive treatment, leukemia)
what is the MoA of Rifampin?
inhibits DNA-dependent RNA polymerase (transcription inhibitor)
bactericidal effect
what is the mechanism of resistance of Rifampin?
alteration of the polymerase enzyme
which agents are given prophylaxis TB?
Isoniazid (INH) or Rifampin
how are TB and leprosy drugs given?
Orally
what are the other indications for Rifampin other than TB?
- leprosy
- in combination with vancomycin–>active against MRSA and PRSP
- Prophylaxis: N.meningitidis, H. influenza, staphylococci
what is the MoA of Ethambutol?
inhibits synthesis of arabinogalactan
what is the mechanism of resistance of Ethambutol
alteration of drug target
which TB drug is an inhibitor of CYP450 enzymes?
Isoniazid
which TB drug is an inducer of CYP450 enzymes?
Rifampin
mechanism of action of Pyrazinamide
unknown
bacteriostatic
mechanism of resistance of Pyrazinamide
mutations in gene encoding enzymes involved in drug activation
which drugs T1/2 ↑ in renal/hepatic impairment?
pyrazinamide
which TB drug should be avoided in pregnancy?
pyrazinamide
which TB agents are prodrugs (activation by catalase)?
isoniazid
pyrazinamide
how long is the phase I TB treatment? (‘RIPE’)
2 months
how long is the phase II TB treatment? (‘RI’)
4-7 months
what is the T1/2 of Isoniazid ?
fast acetylators–> 60-90 min’
slow acetylatos–> 3-4 h’
SE of Isoniazid (6)
- Neurotoxicity due to B₆ deficiency- insomnia, muscle twitching, peripheral neuritis
- sideroblastic anemia
- hepatotoxicity
- drug-induced lupus
- acute hemolysis in G6PD deficient patients
- AG metabolic acidosis
SE of Rifampin (5)
- nephrotoxicity
- skin rash
- thrombocytopenia
- hepatotoxicity
- orange colored secretions (saliva, tears, urine)
SE of ethambutol (2)
- dose-dependent visual disturbances
2. headache, confusion
SE’s of pyrazinamide (4)
- non-gout polyarthralgia
- hyperuricemia
- hepatotoxicity
- skin rash
when do we give 2nd line agents for TB?
when the TB is resistant to the 1st line agents
which drug is used for the treatment of life-threatening associated diseases in TB (meningitis, miliary dissemination, end -organ TB)?
streptomycin
which agents are used when TB is resistant to streptomycin?
Amikacin
Kanamycin
what are streptomycin, Amikacin and kanamycin?
Aminoglycosides
protein synthesis inhibitor
what is Cycloserine?
cell wall active Ab
cyclic analogue of D- ala–> inhibits peptidoglycan synthesis
what is Ciprofloxacin and Oflxacin?
2nd gen’ fluoroquinolones
nucleic acid synthesis inhibitor
what is Linezolid?
protein synthesis inhibitor
what does MDR TB mean?
multidrug resistant M. Tuberculosis
resistant to at lease Isoniazid and Rifampin
what does XDR TB mean?
extensively drug-resistant M. Tuberculosis
resistant to fluoroquinolones and at least 1 additional 2nd line drugs
how do we treat MDR -TB and XDR-TB and for how long?
extensive use of 2nd line agents
18-24 months
+12 months after sputum culture is negative
maybe surgery for lung abscess
what are the drugs used for leprosy?
Dapsone+Rifamin +/- Clofazimine
which drug is also used as an alternative treatment for Pneumocystis jirovecii pneumonia in AIDS patients
Dapsone
what is the T1/2 of Clofazimine?
up to 2 m’
what is the mechanism of Dapsone?
inhibits folic acid synthesis
bacteriostatic
what is the mechanism of clofazimine?
unknown
bacteriostatic
what are the side effects of Dapsone?
GI symptoms
skin rash, fever
methemoglobinemia
acute hemolysis in G6PD deficient patients
what are the drugs used against M. avium complex?
Clarithromycin +Ethambutol +/-Rifabutin
*prophylaxis treatment in AIDS patients
