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General Pharm > Anti-TB Agents > Flashcards

Anti-TB Agents Flashcards

1
Q

Standard Active Tb Therapy Length

A

2 month initial phase and a continuation phase of either 4/7 months

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2
Q

Initial Therapy with Active TB

A

INH, Rifampin, Pyrazinamide, Ethambutol

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3
Q

Two Factors that Increase the Risk of Treatment Failure and Relapse

A

Cavitary disease at presentation

Positive sputum cultures taken at 2 months

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4
Q

Combinatorial TB Therapy

A

1) INH/Rifampin 9 months

2) INH/Rifampin 6 months and Pyrazinamide 2 months

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5
Q

When patients are unable to tolerate >2 first line drugs….

A

They should be treated as if they have MDR-TB

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6
Q

Resistance to INH

A

Rifampin, pyrazinamide, ethambutol for 6 moths

Rifampin and ethambutol for 12 months

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7
Q

Resistance to Rifamycins

A

At least 12 months of treatment with INH, ethambutol and FQ

Pyrazinamide for initial 2 months

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8
Q

MDR-TB and XDR-TB Tx

A

Should be treated with daily (not intermittent) DOT therapy

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9
Q

Define MDR-TB

A

Resistant to rifampin and INH

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10
Q

Define XDR-TB

A

Resistant to INH, rifampin, FQ and 1/3 injectable 2nd line drugs (capreomycin, kanamycin, amikacin)

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11
Q

Patients on ART should not be treated with ___ because ___

A

Rifampin, because it induces CYP450 which will accelerate metabolism of protease inhibitors, reducing antiviral efficacy

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12
Q

Patients not on ART with CD4 <50

A

ART initiation after Anti-TB decreases risk of HIV associated infections and death
Adverse events increases during early co-admin

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13
Q

Patients not on ART with CD4 >50

A

Wait until after initial TB treatment to begin ART to reduce risk of adverse events and IRIS

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14
Q

Patients on Immunomodulating drugs particularly TNF-a inhibitor with LTBI

A

Cases increased risk for active disease, should begin Anti-TB before initiating TNF-a inhibitor

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15
Q

LTBI in Pregnancy

A

Delay Tx 2-3 months after delivery

Hepatotoxicity/tetratogenicity risk

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16
Q

When should you not delay Tx of a LTBI in pregnancy?

A

With HIV positive women or recently Tb infected

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17
Q

Active Tb in Pregnancy

A

Risk of TB greater to fetus than risk of adverse drug effects

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18
Q

ATBI Tx in Pregnancy?

A

INH + Rifampin + Ethambutol 2 months

Isoniazid + Rifampin 7 months

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19
Q

Pregnant and breast feeding mothers taking Isoniazid should also take?

A

Pyridoxine

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20
Q

What causes congenital deafness?

A

Streptomycin

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21
Q

Ethambutol MOA

A

Inhibits mycobacterial arabinosyl transferases encoded by embCAB operon
Transferase involved in polymerization of arabinoglycan component of mycobacterial cell wall

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22
Q

Ethambutol Indications

A

Higher dose in TB menigitis

Atypical mycobacterial infections

23
Q

Ethambutol ADR and Resistance

A

Retrobulbar neuritis –> Loss of visual acuity and red green color discrimination
R: Over expression of emb gene products, mutations in emb gene

24
Q

Isoniazid MOA

A

Inhibits synthesis of mycolic acids

Forms covalent complex with AcpM and KasA blocks mycolic acid synthesis and kills the cell

25
Q

Isoniazid biotransformation requires

A

N-acetyltransferase Phase II biotransformation followed by P450 enzyme-mediated Phase I

26
Q

Rapid v. Slow Acetylators

A

Rapid acetylators half life (< 1hr) about 1/3 to 1/2 that of slow acetylators (3hrs)
Rapid clearance of no therapeutic consequence when appropriate doses administered daily but sub therapeutic concentrations occur if INH is administered as once weekly dose of if there is malabsorption

27
Q

Isoniazid Indications

A

Most active drug
Susceptible active TB infection and latent TB infection
Single agent tx duration 9 months

28
Q

Isoniazid ADR

A

HEPATITIS with minor increase in liver enzymes - higher risk with older populations, alcoholics and pregnant patients
Clinical hepatitis - loss of appetite, jaundice, RUQ pain –> should stop the drug
PERIPHERAL NEUROPATHY in slow acetylators or predisposition ( malnutrition, alchoholic, diabetes, AIDS, uremia)
CNS toxicity (memory loss, psychosis, seizures)
Neuropathy and CNS ADR reversible with PYRIDOXINE

29
Q

Isoniazid CI

A

Pt who develop hepatitis or have a serious rxn

30
Q

Isoniazid Resistance

A

DELETE KatG or KasA
INCREASE inhA or ahpC

Mutations –> over expression of inhA
Mutation/deletion of KatG (activates the prodrug)
Promotor mutation with over expression of ahpC
Mutations in KasA

31
Q

Pyrazinamide Indications

A

MOA unknown

Used with INH and rifampin in short course regiments

32
Q

Pyrazinamide ADR

A

Hepatotoxicity

HYPERURICEMIA: arthralgias and joint pain

33
Q

Pyrazinamide Resistance

A

Impaired uptake of PZA

Mutations in pncA

34
Q

Rifampin MOA

A

Binds to beta subunit of DNA dependent RNA polymerase inhibits RNA synthesis
Bactericidal for mycobacterial

35
Q

Rifampin Indications

A

Mycobacterial infections with INH for active TB
Single agent for latent TB in pt who can’t take INH
Menigococcal carriage
Prophylaxis for H.influenza
Staph carriers or other serious staph infections

36
Q

Rifampin ADR

A

Strong P450 inducer
Reduces half lives of drugs metabolized by p450
Orange color urine, sweat, tears, contact lenses
Rash thrombocytopenia, nephritis
Flu like syndrome unless admin less than 2x week

37
Q

Rifampin Resistance

A

Point mutations in rpoB gene

38
Q

Streptomycin MOA

A

Irreversible inhibitor of protein synthesis

Binds to 30S subunit

39
Q

Streptomycin Indications

A

Effective against Mycobacterium Tb, Myco avium complex, Myco kansasii
Injectable drug in severe or life-threatening forms of Tb

40
Q

Streptomycin ADR

A

Ototoxicity with vertigo and hearing loss
Nephrotoxicity
Toxicity dose related
Relative contraindication in pregnancy due to congenital deafness in newborn

41
Q

Streptomycin Resistance

A

rpsL gene mutations (encodes ribosomal protein)

rrs gene mutation

42
Q

Amikacin Indications

A

Used in most multi-drug resistant TB strains, streopmycin resistant and atypical mycobacteria

43
Q

Amikacin/Kanamycin ADR

A

Nephrotoxicity
Ototoxicity
Tinnitus
High frequency hearing loss

44
Q

Aminosalicyclic acid

A

Folate synthesis antagonist
Not distributed to CNS
Causes GI ADR peptic ulcer hemorrhage, HS rxns can be severe and drug should be stopped

45
Q

Capreomycin

A

Peptide protein synthesis inhibitor
ADR include nephrotoxic, ototoxic, significant pain and abscess formation at injection site
Rrs mutations confer resistance

46
Q

Cycloserine

A

Inhibitor of cell wall synthesis
Toxic effects in 25% of pt
Peripheral neuropathy
CNS dysfunction

47
Q

Ethionamide

A

Related to INH blocking synthesis of mycolic acids
Hepatotoxicity
Intense gastric irriation
Neurologic adverse effects alleviated by pyridoxine

48
Q

Fluoroquinolones

A

Block DNA synthesis by inhibiting DNA gyrase
Used for pt with TB resistant to fire line agents
Well tolerated

49
Q

Linezolid

A

LAST RESORT FOR MDR-TB
Bone marrow suppression
Irreversible peripheral and optic neuropathy

50
Q

Rifabutin

A

Rifamycin derivative
Inducer of CYP450 enzymes
TB, MAC and M.fortuitum
Indicated in preference of RIF in pt with HIV who are on ART with protease inhibitors or NNRTIs

51
Q

When is Rifabutin preferred over Rifamycin?

A

Indicated in preference of RIF in pt with HIV who are on ART with protease inhibitors or NNRTIs

52
Q

Rifapentine

A

Long acting analog of rifampin
Active against TB and MAC
Indicated for Tx of RIF-suspectible TB during continuation phase (after 2 mon therapy and conversion of sputum cultures to negative)

53
Q

Clofazime

A

Used in M.leprae sulfone resistant or when pt are intolerant to sulfones
Skin discoloration from red/brown to black with GI intolerance

54
Q

Dapsone

A

Inhibits folate synthesis
Treatment of leprosy
Treat in PCP and AIDS pt
ADR include hemolysis and methemoglobinemia

General Pharm (5 decks)

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