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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
Isoniazid biotransformation requires
N-acetyltransferase Phase II biotransformation followed by P450 enzyme-mediated Phase I
26
Rapid v. Slow Acetylators
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
Isoniazid Indications
Most active drug Susceptible active TB infection and latent TB infection Single agent tx duration 9 months
28
Isoniazid ADR
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
Isoniazid CI
Pt who develop hepatitis or have a serious rxn
30
Isoniazid Resistance
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
Pyrazinamide Indications
MOA unknown | Used with INH and rifampin in short course regiments
32
Pyrazinamide ADR
Hepatotoxicity | HYPERURICEMIA: arthralgias and joint pain
33
Pyrazinamide Resistance
Impaired uptake of PZA | Mutations in pncA
34
Rifampin MOA
Binds to beta subunit of DNA dependent RNA polymerase inhibits RNA synthesis Bactericidal for mycobacterial
35
Rifampin Indications
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
Rifampin ADR
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
Rifampin Resistance
Point mutations in rpoB gene
38
Streptomycin MOA
Irreversible inhibitor of protein synthesis | Binds to 30S subunit
39
Streptomycin Indications
Effective against Mycobacterium Tb, Myco avium complex, Myco kansasii Injectable drug in severe or life-threatening forms of Tb
40
Streptomycin ADR
Ototoxicity with vertigo and hearing loss Nephrotoxicity Toxicity dose related Relative contraindication in pregnancy due to congenital deafness in newborn
41
Streptomycin Resistance
rpsL gene mutations (encodes ribosomal protein) | rrs gene mutation
42
Amikacin Indications
Used in most multi-drug resistant TB strains, streopmycin resistant and atypical mycobacteria
43
Amikacin/Kanamycin ADR
Nephrotoxicity Ototoxicity Tinnitus High frequency hearing loss
44
Aminosalicyclic acid
Folate synthesis antagonist Not distributed to CNS Causes GI ADR peptic ulcer hemorrhage, HS rxns can be severe and drug should be stopped
45
Capreomycin
Peptide protein synthesis inhibitor ADR include nephrotoxic, ototoxic, significant pain and abscess formation at injection site Rrs mutations confer resistance
46
Cycloserine
Inhibitor of cell wall synthesis Toxic effects in 25% of pt Peripheral neuropathy CNS dysfunction
47
Ethionamide
Related to INH blocking synthesis of mycolic acids Hepatotoxicity Intense gastric irriation Neurologic adverse effects alleviated by pyridoxine
48
Fluoroquinolones
Block DNA synthesis by inhibiting DNA gyrase Used for pt with TB resistant to fire line agents Well tolerated
49
Linezolid
LAST RESORT FOR MDR-TB Bone marrow suppression Irreversible peripheral and optic neuropathy
50
Rifabutin
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
When is Rifabutin preferred over Rifamycin?
Indicated in preference of RIF in pt with HIV who are on ART with protease inhibitors or NNRTIs
52
Rifapentine
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
Clofazime
Used in M.leprae sulfone resistant or when pt are intolerant to sulfones Skin discoloration from red/brown to black with GI intolerance
54
Dapsone
Inhibits folate synthesis Treatment of leprosy Treat in PCP and AIDS pt ADR include hemolysis and methemoglobinemia

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