C2. Antimycobacterial drugs Flashcards
What are Mycobacteria?
- Mycobacteria are slow-growing aerobic, non-motile rods with a resistant lipid-rich wall.
- They are facultative intracellular pathogens and can remain dormant.
List the 1st line anti-TB medications.
“RIPE” Drugs:
- Rifampin (RA)
- Isoniazide (INH)
- Pyrazinamide (PZA)
- Ethambutol (ETB)
List the 2nd line anti-TBC meds.
- Ethionamide
- Cycloserine
- PAS (para-aminosalicylic acid)
- Kanamycin/Amikacin
- Capreomycin
- Fluoroquinolones
- Rifabutin
- Linzolid
- Bedaquiline
- Delamanid
List the anti-leprosy meds.
- Dapsone
- Rifampin
- Clofazemine
List the agents used to treat Mycobacterium Avium Complex (MAC) infection.
Mneumonic: “AIDS”
- Azithromycin
- Claritromycine
- Ethambutol
- (+/-) Rifabutin
How long do you give First-Line Agents?
You give all 4 for first 2 months then just Rifampin (RA) and Isoniazide (INH) for 4 more months after that.
What considerations should you make regarding the Drug Distribution of the anti-TB medications?**
- In younger, well-vascularized, cellular granulomas → anti-TBC drugs must enter interstitium and penetrate immune cells to enter phagolysosomes where bacteria are In necrotic granulomas / cavities → drugs must diffuse through the caseated material to reach extracellular pathogens
What is the MOA of Nitrofurantoin?
Nitrofurantoin concentrates in urine and is reduced inside bacteria by flavoproteins → highly reactive intermediates → cause damage to ribosomes, DNA and metabolic processes.
What is the MOA of Bacitracin?
Bactracin is used topically and it inhibits a carrier for transfer of peptidoglycan subunits → disrupts cell wall synth of the bacteria.
What is the MOA of Phosphomycin?
Phosphomycin is administered as prodrug called trometamol. It inhibits the formation of N-acetyl muramic acid → cell wall synth disruption.
What is the MOA of Colistin?
Colistin also known as polymyxin E is a cationic detergent → membrane disruption.
What is Mycobacterium Avium Complex (MAC)?**
- Common in systemic disease in AIDs patients with CD count <50 can use azithromycin/clarithromycin with ethambutol +/- rifabutin
- Mycobacterium avium complex is a group of mycobacteria comprising Mycobacterium intracellulare and Mycobacterium avium (No mention of M. chimera in ref) that are commonly grouped together because they infect humans together; this group, in turn, is part of the group of nontuberculous mycobacteria. These bacteria cause disease in humans called Mycobacterium avium-intracellulare infection or Mycobacterium avium complex infection.[2]
What is the MOA of Dapsone?
Dapsone inhibits folate synthesis used in combo with rifampin.
What is Clofazimine used for?
It is used for lepromatous form of leprosy with ‘leonine facies’, from Sketchy.
What is the MOA of Rifampin?
Rifampin inhibits RNA polymerase → bactericidal effect, especially dormant microbes with a long post-antibiotic effect (PAE).
What is the MOA of Linezolid?
Linzolid inhibits protein synthesis.
When is Rifabutin used?
- Rifabutin is similar to rifampin, but less enzyme induction.
- Its used to replace rifampin when treating TBC in HIV patients, due to less interaction with antiretroviral protease inhibitors.
List the Fluoroquinolones.
- ciprofloxacin
- levofloxacin
- gatifloxacin
- moxifloxacin
What is the MOA of Capreomycin and what is it used for?
Capreomycin acts by protein synthesis inhibition and its used for multiresistant M. tuberculosis.
What are the indications for Kanamycin / Amikacin?
They are used in case of streptomycin resistance / multiresistance.
What is the MOA of Para-aminosalicylic Acid (PAS)?
It inhibits folate synthesis as an analog of PABA → bacteriostatic.
What is the MOA of Cycloserine?
Cycloserine is a D-Ala analog → inhibits Ala racemase + thus cell wall synthesis.
What is the MOA of Ethionamide?
It is related to isoniazid and also inhibits mycolic acid synth.
What are the indications of Second-Line TB Agents?
Indicated in resistance to first-line agents or to limit adverse reactions.
What is the MOA of Isoniazid?
- The active metabolites block of isoniazid mycolic acid synth via enzyme/carrier protein inhibition.
- bactericidal in actively growing microbes,
- -static in dormant Mycobacterium
- specific catalase G enzymes create active metabolites within the microbes.
What is the MOA of Pyrazinamide?
Pyrazinamide is a prodrug is converted to activated pyrazinoic acid by mycobacterial pyrazinamidase. The mechanism itself is unknown. It does however seem to cause membrane/metabolism disruption and therefore results in a bactericidal effect, esp. in dormant Mycobacteria. Resistance does develop fast by pyrazinamidase mutations. This drug is not given by itself but in combo with the other “RIPE” drugs.