TB Agents Flashcards
What are the first line TB agents
Isoniazid, Rifampin, Pyrazinamide, ethambutol
When using a multidrug regimen using the first line TB agents which one can be dropped earliest
Ethambutol
What is the MOA to isoniazid
inhibit mycolic acid (fatty acid in cell membrane) by forming NAD-adducts, the NAD-adducts blocks the Inh-A coenzyme binding site
How does resistance occur to isoniazid, what changes
katG, enzyme to active isoniazid is no longer functioning/ inhA, mutations in NADH binding site
What is the toxicity associated with isoniazid
peripheral nephritis if not given with vitamin B6 (pyridoxine), hepatoxicty
What is the MOA of rifampin
inhibits RNA polymerase by binding to the beta subunit therefore inhibiting initiation of transcription
T/F: The use of rifampin will lead to inhibiton of liver enzymes
False: The use of rifampin will lead to induction of liver enzymes
What is a rifampin derivative used in TB coinfection with what disease, when is it used
Rifabutin/ patients with a TB/HIV co-infection when using a protease inhibitor, M. avium-intracellulare infection
Which rifampin derivative has a longer half life and is dosed once weekly in the continuation phase
Rifapentine
What is the enzyme that converts pyrizinamide into its active form, what is the active form
Pyrazinamidase (pncA), pyrazinoic acid
What is the toxicity associated with pyrazinomide
Heptatoxicty
What is the MOA of ethambutol
inhibits arabinsoyl transferase affecting synthesis of arabinoglactan and liproarabinomannan in cell wall
What are the toxicities associated with ethambutol
Optic neuritis
T/F: None of the first line TB drugs are prodrugs that need to be coverted by TB
False: Pyrazinomide and Isoniazid both need to be converted to their active forms by TB in order to work
What are the second line TB agents
Fluroquinolones, oxazolidinones, diarylquinolones
What are the fluroquinolones used against TB
Levofloxacin, moxifloxacin, gatifloxacin
What is the oxazolidinones used against TB, diarylquinolones
Linezolid, Bedaquiline
What is the MOA of fluroquinolones
inhibit DNA gyrase therefore not allowing uncoiling
What is a serious side effect of fluroquinolones
aortic rupture
What are the reasons to bring in new drugs to fight TB
Reduce treatment duration, Succesful treatment against drug resistant TB , cure latent TB infection
T/F: Linezolid inhibits protein synthesis
True
What are the side effects associated with linezolid use
various neuropathies and myelosuppresion
T/F: Nitroaromatics are prodrugs and could be brought to first line over time
True
T/F: Bedaquiline is active against ATP synthase and works well against persistent TB
True
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What are the side effects of bedaquiline
Q-T interval prolongation, hepatotoxicity
What are the third line agents of TB
Imipenem, Clofazimine, Clarithromycin, Thioridazine
If someone has latent TB what are the treatment options and how long are they
Isoniazid alone 9 months, Rapamacin alone 4 months, isoniazid and rifapentene weekly for 3 months
What should be done if there is a single drug resistance to a first line drug in active TB, what is the active TB is resistant to rifampicin
Replace with fluroquinolone, extend to 12 months
T/F: If a patient has a HIV/TB co-infection they should recieve the standard regimen
False: If the patient is receiving anti-retroviral therapy than the standard regimen should be used, if the patient is not receiving anti-retroviral therapy than the continuation phase should be extended by 3 months
What rapamycin derivative should be used if the patient has HIV as well, why
Rifabutin to reduce CYP 450 induction
What sickness can occur when treating TB in patients with HIV due to their immune system being restored, what drugs will treat IRIS
Immune Reconstitution Inflammatory Syndrome (IRIS)/ mild-ibuprofen, severe- corticosteroids
What are the two main organisms that cause tuberculosis besides M. tuberculosis
M. avium and M. abscessus
What is a way to have resistance against pyrazinamide
PncA mutation
What are resistance mechanisms against ethambutol
Overexpression of embA, embB, or embC/ mutations in embB
T/F: Mutations in gyrA can lead to fluroquinolone resistance
True
