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TB Pharm Flashcards

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1
Q

What populations are at an increased risk of active disease?

A

HIV and children

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2
Q

How is TB diagnosed based on initial suspicion?

A

Respiratory symptoms
abnormal CXR (upper lobe infiltrates & cavities)
Positive acid-fast bacilli-stained smear

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3
Q

What is the definitive diagnosis for TB?

A

Isolation of M tub from clinical specimen

May take 3-8 weeks for clinical report to come back

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4
Q

What is the general treatment regimen for TB?

A

Intensive phase - 4 drug regimen
Continuation phase

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5
Q

What are the first line agents for active tuberculosis treatment?

A

Isoniazid - tabs/IV/IM
Rifampin - capsule/IV
Rifapentine - tab
Rifabutin - cap
Ethambutol - tab
Pyrazinamide - tab

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6
Q

What are the second like agents for active TB treatment?

A

Streptomycin
Amikacin
Capreomycin
Ethionamide
Cycloserine
p-aminosalicylic acid
levofloxacin
moxifloxacin

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7
Q

Describe the initial vs continuation phase?

A

initial - bactericidal phase
-eliminates majority of bacteria
-resolves symptoms and infectiousness

Continuation phase - sterilization phase
-phase that kills persisting mycobacteria

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8
Q

What is the duration of treatment of drug susceptible TB

A

minimum 6 months

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9
Q

What is the traditional regimen of TB treatment?

A

Intensive phase - 2 months
-Isoniazid
-Rifampin
-Ethambutol
-Pyrazinamide

Continuation phase - at least 4 months
-Isoniazid
-Rifampin

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10
Q

What should guide the approach to management for treating active disease?

A

Sputum acid fast bacilli culture results at 2 months AND presence or absence of cavitary disease on CXR at initiation

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11
Q

What are the required doses of the intensive phase to ensure treatment completion?

A

60 doses with daily therapy administered in 3 months

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12
Q

What are the required doses of the continuation phase to ensure treatment completion?

A

All doses for 4 month phase should be delivered in 6 months
All doses for 6 month phase should be completed in 9 months

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13
Q

What should be done after the continuation phase?

A

CXR comparison

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14
Q

What is considered interrupted treatment and what should be done?

A

Number of doses unable to be administered in the targeted time period

Determine whether to extend duration of treatment or restart treatment

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15
Q

When is continuous treatment more important? Why?

A

The intensive phase
-organ burden highest
-drug resistance greatest

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16
Q

What is the relationship between rifampin and hepatotoxicity?

A

Cholestatic pattern - increased bilirubin and alkaline phosphatase

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17
Q

Which drugs will cause elevated serum transaminase concentrations?

A

Isoniazid, rifampin, pyrazinamide

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18
Q

What should be included in patient education if meds cause GI upset

A

common in first few weeks

take meds with food

DO not discontinue unless absolutely necessary

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19
Q

Which med can cause peripheral neuropathy?

A

isoniazid

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20
Q

Which meds can cause urine discoloration?

A

rifampin and rifabutin

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21
Q

Which med can cause elevated serum uric acid concentrations (gout)?

A

pyrazinamide

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22
Q

Which med can cause vision disturbances?

A

Ethambutol

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23
Q

What should be included in monitoring for meds?

A

Baseline LFTs
-bilirubin
-alk phos
-ALT/AST

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24
Q

What liver manifestations indicate discontinuation of meds?

A
  1. serum bilirubin >3mg/dL or ALT/AST >5x ULN
  2. Symptoms of hepatitis present ALT/AST >3x UNL
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25
If a med must be discontinued due to hepatotoxicity, what should be used until LFTs <2-3x the UNL
Ethambutol Fluoroquinolone Injectable agent
26
How should hepatotoxic meds be reintroduced if needed discontinued?
one at a time with monitoring between starts of each agent
27
What approach should be taken to restarting HTX meds if the issue had a cholestatic pattern?
This is more often seen with rifampin, so start with isoniazid or pyrazinamide
28
What approach should be taken to restarting HTX meds if there was no increase in hepatic transaminase after 1-2 weeks?
start rifampin first, the isoniazid after 1-2 weeks
29
What should be done when restarting HTX meds if the symptoms reoccur or hepatic transaminases increase?
the last drug added should be stopped
30
What should be done if a patient is tolerating rifampin and isoniazid but having prolonged or severe HTX?
do not rechallenge pyrazinamide extend treatment to 9 months
31
What should be done if a patient is tolerating rifampin and isoniazid and having milder HTX?
pyrazinamide may be rechallenged Rifampin + pyrazinamide + ethambutol can be given for 6 months
32
Which drug has the most D/D interaction and what is it?
Rifamycins (rifampin most potent) CYP450 inducers decrease levels of protease inhibitors and selected nonnucleoside reverse transcriptase inhibitors (HIV tx)
33
What are two important pt ed points?
1. compliance is critical to treatment 2. take all meds at the same time to reduce risk of drug resistance
34
What are the two fixed dose combination products and their benefits?
1. INH/RIF (rifamate) 2. INH/RIF/PZA (Rifater) easier administration less pill burden reduce dosing errors
35
Isoniazid MOA?
inhibits synthesis of mycolic acids (cell wall component) Bactericidal at therapeutic levels
36
Rifampin MOA?
inhibit bacterial DNA-dependent RNA polymerase Concentration dependent
37
Ethambutol MOA?
inhibits arabinosyl transferase resulting in impaired mycobacterial cell wall synthesis
38
Pyrazinamide MOA?
converted to pyrazinoic acid in susceptible strains which lowers the pH of the environment exact mechanism unclear
39
What is the treatment duration for latent TB?
9 month daily isoniazid regiment
40
What is the completion rate of self-administered plans with latent TB?
60%
41
What is an alternative to the standard 9 month plan for latent TB treatment
Combination of isoniazid and rifapentine administered once weekly for 12 weeks with directly observed therapy better compliance with = efficacy
42
What do most pregnant patients with latent TB choose to do?
Defer treatment until 3 months after delivery
43
Which groups of pregnant women should under treatment for latent TB while pregnant?
Recent contact with a patient untreated with active respiratory TB HIV-infected pt with CD4 count <=350
44
Which treatment regimen is recommended for pregnant patients with latent TB?
Rifampin -effective -favorable completion rates -low HTX
45
What regiment for pregnant patients with active TB undergo?
1. Isoniazid + rifampin + ethambutol x 2 months 2. Then isoniazid + rifampin x 7 months -total 9 month treatment
46
What are the risk factors of resistant TB for patients without a history of TB
1. Exposure to drug-resistant TB 2. travel/living somewhere with high prevalence of DR-TB 3. work/reside in setting with documented DR-TB 4. Emigration within previous 2 years from region with known DR-TB
47
What are the risk factors of resistant TB for patients with a history of TB
1. Progressive clinical/radiographic findings while on TB treatment 2. Lack of conversion of cultures to negative during first 3 months of tx 3. Noncompliance with TB tx 4. Documented tx failure or relapse 5. Inappropriate treatment regimen
48
What is the empiric treatment for drug resistance?
Isoniazid + rifampin + pyrazinamide + 2 additional drugs 1. fluoroquinolone (levo or moxi) 2. second line agent
49
What are the steps to treatment of DR-TB
Isoniazid + rifampin + pyrazinamide step 1 - choose levo or moxi step 2 - bedaquiline + linezolid step 3 - clofazime + cycloserine/terizidone
50
Define monoresistant TB?
TB caused by an isolate of M tub that is resistant to a single antituberculous agent
51
Define polyresistant TB
isolate of TB resistant to more than one antituberculous agent - either isoniazid OR rifampin (not both)
52
Define multidrug resistant TB?
TB caused by an isolate of M tub that is resistant to at least both isoniazid AND rifampin
53
Why are second line agents not as effective?
-decreased activity against m tub -unfavorable pharmacokinetic profile -increased adverse effects
54
Outline capreomycin
needs at least 9 months ADE: -ototoxic -vestibular toxicity -nephrotoxicity -electrolyte disturbances -local pain with IM injection AVOID in pregnancy
55
Outline cycloserine?
ADE - CNS toxicity Monitoring: -CNS monitoring ideally monthly -serum concentration levels -renal dosing requirements
56
Outline Ethionamide
ADE: -GI -HTX -neurotoxicity -endocrine: DM hypothyroid, gynecomastia Monitor: -LFTs -TSH baseline & monthly Pt ed - take with food
57
Outline fluoroquinolones?
ADE: -GI -H/A -dizziness -QT prolongation -Achilles tendonitis needs renally dosed
58
What is pneumocystis jirovecii pneumonia classified as?
fungal infection spread through the air and to immunocompromised patients by healthy adult carriers
59
What increases risk of infection for PJP?
immunosuppression (diseases and steroids)
60
How is PJP diagnosed?
Sputum sample - bronchoalveolar lavage Lung biopsy Blood test (B-D-Glucan; part of cell wall)
61
What is the treatment of choice for PJP?
Bactrim (T/S)
62
What decides if patient is clinically stable or not with PJP?
PaO2 >=60mmHg, RR<25 oral vs IV consideration
63
What should be done if a patient with PJP has a sulfa allergy?
consider desensitization
64
What should be done if a patient has a sever allergy to sulfa drugs (like SJS)
do not desensitize and avoid sulfa drugs
65
What should be monitor with T/S treatment?
hyperkalemia
66
What are the ADEs of T/S?
Fever neutropenia rash hyperkalemia
67
What should be given as an alternative treatment for PJP if T/S not an option (mild disease)
1. Atovaquone - preferred 2. Clindamycin + Primaquine 3. TMP + Dapsone
68
What should be given as an alternative treatment for PJP if T/S not an option (moderate disease)
1. Clindamycin + Primaquine 2. TMP + Primaquine
69
What should be given as an alternative treatment for PJP if T/S not an option (severe disease)
1. Clindamycin + Primaquine - preferred 2. IV Pentamidine - very toxic
70
Outline IV pentamidine
often not used due to toxicity but potentially as effective as T/S ADE: -hypotension -hypoglycemia -nephrotoxicity -pancreatitis
71
What should be given with atovaquone?
high fat meal to help with absorption
72
How long should treatment for PJP be?
21 days
73
PJP - When should non HIV patients see improvement and when should it be considered that treatment may have failed?
7 days for both
74
What should be done after 21 days of treatment for PJP and why?
decrease dose to prophylactic dose to prevent recurrent infection
75
What may be a potential benefit of adjunctive glucocorticoid therapy in the treatment of PJP?
potential benefit for lung inflammation
76
What is the mortality rate of PJP in untreated patients?
90-100%

Pulmonary Unit (12 decks)

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