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30 Cards in this Set
- Front
- Back
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Whats the MoA of isoniazid against TB?
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Isoniazid inhibits mycolic acid synthesis in TB cell walls.
Isoniazid (which is a prodrug) is activated by the TB enzyme katG to an active metabolite that binds to NAD+ and inhibits a fatty acid synthase II (FAS II) enzyme called enoyl-ACP-reductase, which is required to make mycolic acid |
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Whats the MoA of ethionamide against TB?
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The same MoA as isoniazid
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Does isoniazid cross the BBB?
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yes
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What are the MoA's for isoniazid?
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Mutation in katG(no activation of isoniazid)
Mutation in the inhA gene that codes for enoyl-ACP-reductase(decreased affinity for isoniazid?) |
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What must we also do for TB patients who are:
-diabetics -HIV patients -pregnant -alcoholics -have poor nutrition -are taking over 300mg/day of isoniazid |
These patients have lower than normal levels (or absorption) of vitamin B6, and must be supplemented with pyridoxine/B6 or they will have paresthesias(tingling, burning, numbness of the skin)
note: isoniazid competes with B6 for some enzymes |
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What are the AE's of isoniazid?
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Hepatitis/jaundice(isoniazid has nitrogen in it, which is metabolized by the liver and converted into ammonia)
Rash Fever Poorly formed RBCs Arthritis CNS(euphoria/psychosis/memory loss/seizures) |
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Whats the MoA of the rifamycins(eg rifampin, rifabutin, rifapentine)?
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They inhibit bacterial DDRP(DNA Dependent RNA Polymerase), which is needed to initiate transcription
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What is the main MoA of resistance to the rifamycins?
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Mutation of DDRP to dec binding affinity with the drug
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Do the rifamycins cross the BBB?
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yes
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What is unique about rifampin's ADME?
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Rifampin has enterohepatic recirculation
It also crosses the placenta and might be teratogenic May color body fluids and contact lenses, so must counsel patients |
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What are the AE's of rifampin?
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Rash
Fever N&V Hepatitis |
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Whats the difference between isoniazid and rifampin in terms of their affects on CYP450?
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Isoniazid can reduce CYP450 enzymes
Rifampin can induce CYP450 enzymes wiki: this is one of the reasons why these are coadministered together, and also because they have synergistic MoA's |
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Which rifamycins have the greatest to least induction of CYP's?
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Rifampin(most)
Rifapentin Rifabutin(least) |
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Whats the MoA of Ethambutol?
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Inhibits arabinosyl transferase that attach arabinosides to the cell wall, thereby inhibiting cell wall synthesis
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What is the MoA of resistance to Ethambutol?
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Upregulation of arabinosyl transferase
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Does Ethambutol cross the BBB?
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yes
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What is the main AE of Ethambutol?
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Neuritis (due to toxicity in optic nerve), causes:
-Dec'd acuity/sharpness -Color blindness(red from green) -Dec'd accommodation/far vision |
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What is the MoA of Pyrazinamide?
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Very similar to isoniazid and ethionamide
Pyrazinamide is a prodrug that gets activated to pyrazinoic acid by TB pyrazinamidase (like katG did for isoniazid) pyrazinoic acid (binds to NAD?) and inhibits FAS I (not FAS II), which inhibits mycolic acid synthesis in the cell wall |
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Does Pyrazinamide cross the BBB?
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yes
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What is the main AE of Pyrazinamide?
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Hepatitis(must monitor liver enzymes throughout therapy)
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What antiTB drugs are given for LATENT TB, and for how long?
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Isoniazid (for 6-9 months) OR Rifampin (for 4 months)
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What antiTB drugs are given for ACTIVE TB, and for how long?
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Take the following 4:
Isoniazid (for 6 months) Rifampin (for 6 months) Pyrazinamide (for 2 months) Ethambutol (for 2 months) |
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What antiTB drugs are given for DRUG RESISTANT ACTIVE TB, and for how long?
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Take the 4 drugs for active TB previously mentioned, but for 2 years, AND take a second line antibiotic for 2 years as well
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List the second line TB drugs?
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Fluoroquinolones
Ethionamide Cycloserine Linezolid(an oxazolidinone) Para-aminosalicylic acid And the following aminoglycosides: Capreomycin Kanamycin Amikacin Streptomycin |
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What is it called when a health care professional personally witnesses the TB patient taking his medication, for each dose, for the duration of therapy?
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DOT (directly observed therapy)
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What is MDR?
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Mycobacteria (tuberculosis) Drug Resistance (refers to strains that are resistance to the 4 first line drugs)
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What is XDR?
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eXtended Drug Resistance (refers to TB bacteria that are resistance to the 4 first line drugs + many of the second line ones as well)
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Whats the MoA of para-aminosalicylic acid?
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Its an analog/mimic of PABA (like sulfonamides)
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What is the MoA of Cycloserine?
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Its an analog of alanine, which is a component of the peptidoglycan cell wall
Cycloserine interferes with cell wall synthesis |
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Which one is added when isoniazid resistant MDR TB is confirmed:
A. Pyrazinamide B. Rifampin C. Moxifloxacin D. Vancomycin |
C. Moxifloxacin (fluoroquinolone)
note: Pyrazinamide and Rifampin are part of first line cocktail, and Vancomycin is just not for TB in any fashion |
