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Pulmonology 2 > Pharm - Tb > Flashcards

Pharm - Tb Flashcards

1
Q

A person w/ latent Tb infection:

A
  • usually has skin test/blood test results indicating Tb
  • normal CXR and neg. sputum test
  • Tb bacteria in body that are alive but inactive
  • does not feel sick
  • cannot spread to others
  • needs tx for latent infection to prevent dz
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2
Q

DOT (directly observed therapy)

A

someone has to watch the person take treatment

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3
Q

What are the 4 drugs used to treat latent Tb?

A
  • Isoniazid (INH)
  • Rifampin
  • INH w/ rifapentine
  • ING w/ rifampin
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4
Q

mechanism of action for INH

A
  • selective for mycobacteria
  • causes cell dath by inhibiting enzymes associated w/ mycolic acid sysnthesis, an essential component of bacterial cell wall
  • bactericidal
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5
Q

spectrum of activity of INH

A
  • active against intracellular and extracellular mycobacterium tb
  • at therapuetic levels isoniazid is bactericidal against actively growing intra and extracell mycobacterium tb
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6
Q

indications for the treatment of INH

A
  • latent Tb infection

- active Tb

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7
Q

contraindications for the treatment of INH

A
  • hypersensitivity reaction sto isoniazid
  • hx of drug-induced hepatitis
  • actue liver dz
  • Hx of hepatic injury secondary to INH
  • Hx of sever adverse rxn to INH
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8
Q

Duration of INH tx of latent Tb

A
  • 9 mos recommended

- 6 mos can be considered to reduce cost and improve adherence

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9
Q

drug interactions with INH

A
  • phenytoin (anticonvulsant) - INH could increase serum concentration
  • carbamazepine (anticonvulsant) - INH could increase hepatotoxic effects
  • always check w/ pharmacist for interactions
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10
Q

monitoring parameters of INH

A
  • baseline and periodic LFTs (ALT AST)
  • sputum cultures monthly (until 2 consecutive negatives)
  • monitor for prodromal signs of hepatitis (fatigue, anorexia, nausea, upper quadrant pain)
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11
Q

hepatitis associated w/ INH

A
  • *most important side effect
  • can be fatal
  • can occur after months of tx
  • risk is age related
  • incidence is 1 in 1000
  • most likely to occur in those who drink alcohol
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12
Q

Peripheral neuropathy occurs in about 2% of INH patients; what can be done to prevent it?

A

pyridoxine supplementation

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13
Q

mechanism of action of rifampin

A
  • *red flags should go up in brain when you see this drug**
  • binds to DNA-dependent bacterial RNA polymerase
  • blocks RNA transcription and protein synthesis
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14
Q

spectrum of activity of rifampin

A
  • intracellular penetration is high so it’s useful for tx of intracellular pathoens
  • primary use is for latent and active Tb
  • bactericidal against most
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15
Q

indications for the tx of rifampin

A

-management of active and latent tb in combo w/ other agents

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16
Q

contraindications for use of rifampin

A
  • hypersensitivity to rifampin

- concurrent use of antiretroviral or protease inhibitors

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17
Q

most common ADRs in rifampin

A
  • rash
  • GI distress
  • increased LFTs (hepatitis is rare)
  • flu-like syndrome
  • orange-red discoloration of body fluid
  • CBC changes like thrombocytopenia, leukopenia, anemia
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18
Q

most notable ADRs in rifampin

A
  • red/orange disocoloration of urine, feces, saliva, sweat, tears and CSF
  • advise pts
  • drug is relatively well tolerated
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19
Q

what is significant about the function of rifampin?

A
  • it is a potent CYP3A4 inducer
  • so decreases concentration of many drugs
  • and has LOTS of drug interactions
  • **red flag reminder
20
Q

use of rifampin during pregnancy or in breastfeeding mothers

A
  • it crosses the placenta
  • d/t risk of tb in fetus, tx is recomended when risk of tb in mother is moderate to high
  • its excreted in breast milk
  • d/t potential for serious ADRs to nursing infant its recommended to stop nursing or stop drug
21
Q

indications for use of rifapentine (Priftin)

A

-tx of LTBI and active tb

22
Q

contraindications of rifapentine

A
  • hypersensitivity to rifapentine, other rifamycins or any component in the formulation
  • not effective in tx of latent tb in children <2
  • infection w/ INH or rifampin resistant tb
  • tb w/ HIV infection d/t increased risk of aquired rifampin resistance
  • pregnant or breast feeding women
23
Q

ADRs associated w/ rifapentine

A
  • GI: n/v
  • hepatotoxicity
  • elevated uric acid levels and LFTs
  • orange/red discoloration of body fluid
  • flu-like syndrome
  • hypotension and syncope associated w/ once weekly dosing
24
Q

What is the preferred tx regimen for latent tb?

A
  • INH for 9 mos self administered

- Weekly INH and rifapentine for 3 mos given by DOT

25
Q

What is the alternative tx regimen for latent tb?

A
  • INH for 6 mos
  • INH plus rifampin for 3 mos
  • Rifampin daily for 4 mos is an alternative for INH resistant infections
26
Q

What is the drug of choice for treatment of latent tb during pregnancy?

A
  • ioniazid (5mg/kg/day up to 300 mg daily) for 9 mos
  • can have minor interuptions as long as 270 doses are completed in 12 mos
  • pyridoxine supplementation

Alternative: rifampin daily for 4 mos

27
Q

What is the drug of choice in children for the tx of latent tb?

A
  • INH (10-15 mg/kg daily) for 9 mos
  • alternative: 20-30 mg/kg twice a week w/ DOT
  • monitor frequently
  • in children >2: INH plus rifapentine can be used
  • for children intolerant to INH or w/ resistant organism: rifampin
28
Q

What is the drug of choice for tx of latent Tb in HIV infected pts?

A
  • preferred tx in resource rich setting: INH 300mg daily for 9 mos
  • in resource-limited settings: minimum of 6 most of INH up to 36 mos of tx
29
Q

What drugs are used in the treatment of drug-resistant latent tb?

A
  • for people exposed to single-drug INH or rifampicin, the other drug should be administered as a single agent
  • for people exposed to MDR-Tb:
  • fluoroquinolone alone (levo or moxi)
  • fluoroquinolone plus ethambutol or ethionamide
  • 6-12 mos
30
Q

What is the approach to treatment interruptions in pts w/ latent tb?

A

-the earlier and longer the interruption, the more serious the impact, and greater need to restart therapy from beginning

31
Q

If pt is on a 6-9 mo. regimen of INH and misses more than 3 mos of therapy, what do you do?

A

-reinstitute treatment from beginning

32
Q

For pts treated w/ a 3-4 mo. regimen and miss more than 2 mos of therapy, what do you do?

A

-treatment should be reinstated from beginning

33
Q

What is the treatment of active Tb during the intensive/initial phase?

A
  • 4 drugs: INH, rifampin, pyrazinamide, ethambutol)
  • usually 2 mos (varying schedule)
  • drug-susceptibility testing should be done on all initial isolates to use as guide for tx
34
Q

mechanism of action of pyrazinamide (PZA)

A
  • metabolized to pyrazinoic acid (active form)
  • exact MOA is unknown - greatest activity against dormant or semi dormant orgs w/i macrophages
  • bacteriostatic
  • when used in combo w/ INH and rifampin, has a sterilizing effect
  • not used as monotherapy b/c rapid development of resistance
35
Q

spectrum of activity of PZA

A
  • most commonly used for tx of active tb during initial phase of therapy
  • in combo w/ other agents
  • relatively narrow spectru
36
Q

ADRs associated w/ PZA

A
  • GI
  • arthralgias (very high incidence)*
  • uric acid elevations*
  • hepatotoxicity*
  • photosensitive dermatitis
  • hematologic
37
Q

mechanism of action of ethambutol (EMB)

A
  • inhibits arabinosyl transferase leading to impaired mycobacterial cell wall synthesis
  • bacteriostatic
38
Q

ADRs associated with ethambutol

A
  • **retrobulbar neuritis: optic neuropathy; change in visual acuity and/or color blindess
  • hematologic
  • GI
  • CNS
  • skin rash
39
Q

Describe the treatment of active tb during the continuation phase

A
  • administered for 4 (most pts) or 7 months (for those who require longer)
  • in most cases consists of INH and Rifampin
40
Q

What patient might require the longer continuation phase?

A
  • those w/ cavitary pulmonary tb on initial CXR and positive sputum culture after 2 mos of tx in initial phase
  • those whose initial phase did not inlcude pyrazinamide (pregnancy)
41
Q

What is the approach to treatment interruptions in pts w/ active tb?

A
  • completion of tx is determined by duration of therapy AND total number of doses administered
  • duration:
  • all doses should be delivered in 3mos
  • continuation phase doses should be delivered w/i 6 mos or 9 mos depending on course
  • if # of doses can’t be administered in time frame, have to determine if tx needs restarted or prolonged
  • in general, continuous tx is MORE important in initial phase
42
Q

what is another adverse effect that all drugs can cause?

A
  • rash
  • petechial rash in pt taking rifampin could indicate hypersentitivity
  • if thrombocytopenia then stop drug and monitor platelets
43
Q

What are the VERY important counseling points in the tx of Tb?

A
  • adherence is key
  • GI upset - take w/ food or at bedtime
  • educate pts about sx of hepatitis
  • report visual changes
  • report petechial rashes
44
Q

describe the tx of HIV infected patients w/ active Tb

A
  • generally have poorer prognosis
  • don’t use twice weekly therapy if CD4 cts <100 (once weekly is contraindicated)
  • if currently being treated w/ ART, rifabutin should be used
  • if diagnosed w/ HIV and Tb simultaneously, tx for tb first and ART 2-4 weeks later
45
Q

describe the tx of pregnant or breastfeeding patients w/ active Tb

A
  • initial tx: INH, rifampin and ethambutol for 2 mos followed by INH and rifampin for 7 mos
  • not much data on PZA in pregnancy
  • give pyridoxine supplementation
  • avoid aminoglycosides
  • use cation w/ ethionamide and fluoroquinolones
  • latent tb therapy can be deferred to 2nd trimester
  • most antimycobacterial agents are excreted in breastmilk but appear to be safe
46
Q

describe the tx of children patients w/ active Tb

A
  • similar tx regimens to adults
  • total therapy often extended to 9mos
  • 3 drug initial regimen is permissible
  • rifapentine and ethambutol not considered safe
  • same max doses applied as in adults

Pulmonology 2 (17 decks)

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