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Phar 506 > TB Agents > Flashcards

TB Agents Flashcards

1
Q

What are the first line TB agents

A

Isoniazid, Rifampin, Pyrazinamide, ethambutol

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2
Q

When using a multidrug regimen using the first line TB agents which one can be dropped earliest

A

Ethambutol

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3
Q

What is the MOA to isoniazid

A

inhibit mycolic acid (fatty acid in cell membrane) by forming NAD-adducts, the NAD-adducts blocks the Inh-A coenzyme binding site

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4
Q

How does resistance occur to isoniazid, what changes

A

katG, enzyme to active isoniazid is no longer functioning/ inhA, mutations in NADH binding site

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5
Q

What is the toxicity associated with isoniazid

A

peripheral nephritis if not given with vitamin B6 (pyridoxine), hepatoxicty

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6
Q

What is the MOA of rifampin

A

inhibits RNA polymerase by binding to the beta subunit therefore inhibiting initiation of transcription

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7
Q

T/F: The use of rifampin will lead to inhibiton of liver enzymes

A

False: The use of rifampin will lead to induction of liver enzymes

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8
Q

What is a rifampin derivative used in TB coinfection with what disease, when is it used

A

Rifabutin/ patients with a TB/HIV co-infection when using a protease inhibitor, M. avium-intracellulare infection

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9
Q

Which rifampin derivative has a longer half life and is dosed once weekly in the continuation phase

A

Rifapentine

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10
Q

What is the enzyme that converts pyrizinamide into its active form, what is the active form

A

Pyrazinamidase (pncA), pyrazinoic acid

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11
Q

What is the toxicity associated with pyrazinomide

A

Heptatoxicty

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12
Q

What is the MOA of ethambutol

A

inhibits arabinsoyl transferase affecting synthesis of arabinoglactan and liproarabinomannan in cell wall

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13
Q

What are the toxicities associated with ethambutol

A

Optic neuritis

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14
Q

T/F: None of the first line TB drugs are prodrugs that need to be coverted by TB

A

False: Pyrazinomide and Isoniazid both need to be converted to their active forms by TB in order to work

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15
Q

What are the second line TB agents

A

Fluroquinolones, oxazolidinones, diarylquinolones

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16
Q

What are the fluroquinolones used against TB

A

Levofloxacin, moxifloxacin, gatifloxacin

17
Q

What is the oxazolidinones used against TB, diarylquinolones

A

Linezolid, Bedaquiline

18
Q

What is the MOA of fluroquinolones

A

inhibit DNA gyrase therefore not allowing uncoiling

19
Q

What is a serious side effect of fluroquinolones

A

aortic rupture

20
Q

What are the reasons to bring in new drugs to fight TB

A

Reduce treatment duration, Succesful treatment against drug resistant TB , cure latent TB infection

21
Q

T/F: Linezolid inhibits protein synthesis

A

True

22
Q

What are the side effects associated with linezolid use

A

various neuropathies and myelosuppresion

23
Q

T/F: Nitroaromatics are prodrugs and could be brought to first line over time

A

True

24
Q

T/F: Bedaquiline is active against ATP synthase and works well against persistent TB

A

True

`

25
Q

What are the side effects of bedaquiline

A

Q-T interval prolongation, hepatotoxicity

26
Q

What are the third line agents of TB

A

Imipenem, Clofazimine, Clarithromycin, Thioridazine

27
Q

If someone has latent TB what are the treatment options and how long are they

A

Isoniazid alone 9 months, Rapamacin alone 4 months, isoniazid and rifapentene weekly for 3 months

28
Q

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

A

Replace with fluroquinolone, extend to 12 months

29
Q

T/F: If a patient has a HIV/TB co-infection they should recieve the standard regimen

A

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

30
Q

What rapamycin derivative should be used if the patient has HIV as well, why

A

Rifabutin to reduce CYP 450 induction

31
Q

What sickness can occur when treating TB in patients with HIV due to their immune system being restored, what drugs will treat IRIS

A

Immune Reconstitution Inflammatory Syndrome (IRIS)/ mild-ibuprofen, severe- corticosteroids

32
Q

What are the two main organisms that cause tuberculosis besides M. tuberculosis

A

M. avium and M. abscessus

33
Q

What is a way to have resistance against pyrazinamide

A

PncA mutation

34
Q

What are resistance mechanisms against ethambutol

A

Overexpression of embA, embB, or embC/ mutations in embB

35
Q

T/F: Mutations in gyrA can lead to fluroquinolone resistance

A

True

Phar 506 (37 decks)

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