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Pharmacology > Anti-tubercular therapies > Flashcards

Anti-tubercular therapies Flashcards

1
Q

What is the only evidence of tuberculosis?

A

a tiny, fibrocalcific nodule at the site of the infection

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2
Q

What is a latent infection?

A

viable organisms that are capable of infection that can remain dormant for decades

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3
Q

How can you tell if a person has a latent TB infections?

A

A tuberculin skin test will be positive but there is no disease

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4
Q

How can you tell if a person has an active TB infection?

A
  • clinical signs and sx
  • radiographic evidence
  • bacteriological evidence
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5
Q

Describe the signs and sx of TB.

A
  • pulmonary cavitation
  • mycobacteria dissemination
  • presence of bacilli in sputum
  • malaise, anorexia, weight loss, fever
  • increased sputum
    extrapulmonary effects
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6
Q

Which bacteria cause TB?

Give some info about them.

A 
mycobacterium TB
- most frequent
mycobacterium bovis
- rare in developed nations
found in TB cows and unpasteurized milk
- oropharyngeal and intestinal TB
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7
Q

What are some characteristics of M. tuberculosis?

A
  • acid-fast bacillus
  • high lipid content of cell wall –> GM-
  • slow growing
  • resistant to drying, most antibiotics and host killing.
  • intracellular survival
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8
Q

How is TB spread?

A
  • by inhaled droplet nuclei

- once a droplet lands on something it is no longer infectious

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9
Q

What happens when TB droplets are inhaled?

A
  1. macrophages with kill the organism

2. macrophages will be unable to kill the organism –> replicates in the macrophage and lead to primary infection

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10
Q

Describe how reactivation happens.

A
  • caused by a loss of balance between immune system and bacilli
  • most often occurs in the lungs but can occur in lymph nodes, plural space, kidneys, gut, CNS
  • pt will be symptomatic
  • infectious if pt has pulmonary TB
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11
Q

Name 2 groups of people who are more likely to have a reactivation of TB

A
  • pts with AIDS

- pts with HIV

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12
Q

What is TB therapy based on?

A

Stage

- latent or active

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13
Q

TB is primarily treated with antibiotics. Why is there such a higher amount of treatment failure and drug resistance?

A
  • long duration of antibiotics with poor adherence
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14
Q

How long is a standard treatment for TB

A
  • 6 months

- 9-12 months for TB meningitits

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15
Q

Why it the treatment so long for TB?

A
  • a prolonged course of antibiotics is required to kill the semi-dormant and dormant organisms
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16
Q

Why is monotherapy not usually used?

A

because it allows selective growth of the resistant organisms and gives rise to drug resistance

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17
Q

What are the first line drugs for TB?

A

Isoniazid
Rifampin
Pyrazinamide
Ethambutol

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18
Q

What is the advantage of using both bacteriostatic and bactericidal drugs?

A

The bacteriostatic drugs will kill off the active bacteria while the bactericidal drugs will kill the dormant/semi-dormant bacteria

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19
Q

What does isoniazid do?

A
  • bactericidal in extracellular area with high oxygen concentration
  • prevents resistance by killing off rapidly growing bacilli
  • high early bactericidal activity
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20
Q

What does rifampin do?

A
  • bactericidal in extracellular areas
  • ONLY drug that in bactericidal in fibrotic areas
  • many drug-drug interactions
  • without rifampin –> 18 months of tx required
21
Q

What does pyrazinamide do?

A
  • important in sterilizing semi-dormant bacteria
  • active in acidic environment
  • loses activity as inflammation resolves
  • no benefit after 2 months
  • allows 6 months of therapy when used with rifampin
22
Q

What does ethambutol do?

A
  • primarily used to prevent resistance to rifampin when primary resistance to isoniazid may be present
  • D/C if organism sensitive to isoniazid
  • DON’T use in renal failure or children
23
Q

What are the 2 phases of TB standard tx regimen?

A 
Intensive phase (0-8 weeks)
Continuation phase (2-6 months)
24
Q

What is the goal of the intensive phase?

A

to quickly kill the rapidly dividing organism to control disease and render the pt non-infectious and prevent emergence of drug resistance

25
Q

What is the goal of the continuation phase?

A
  • to sterilize the lungs by killing dormant/semi-dormant organisms to prevent relapse
  • DOT allows for intermittent therapy
26
Q

Which drugs are used during the intensive phase?

A
  • all 4
  • either 7/7 or 5/7
  • ethamburol can be dropped if organism pansensitive
27
Q

Which drugs are used during the continuation phase?

A
  • isoniazid and rifampin twice a week
28
Q

How is therapy carried out for pansensitive TB?

A
  • duration = number of doses (tx will be extended in order to get all doses in)
29
Q

With pansensitive TB, why would 9 months of therapy be needed?

A
  • if pyrazinamide was NOT used in the first 2 months

- if culture results were positive at 2 months

30
Q

What is the drug therapy used for latent TB?

A
  • isoniazid daily for 9 months

- rifampin daily for 4 months

31
Q

What are mycolic acids?

Which drug inhibits them?

A
  • unique and essential mycobacteria cell wall components

- isoniazid and pyrazinamide

32
Q

What happens if a pt develops abnormal LFTs on therapy?

A
  • must hold TB meds until ALT returns to less than 2x the upper limit
33
Q

What drug therapy do you use once a pt’s ALT level returns to less than 2x the upper limit

A
  • restart rifampin alone or with ethambutol
  • repeat ALT on day 3
  • if ALT is still consider extending therapy to 9 months)
34
Q

What is different in the TB treatment for pts with pre-exisiting liver disease?

A
  • should avoid pyrazinamide
35
Q

What is the TB drug therapy for a pt with cirrhoisis

A

rifampin + ethambutol +fluoroquinolon

36
Q

Describe the TB drug therapy phases for a pt with renal insufficiency/ESRD

A

Intensive
- isoniazid/rifampin 1d after meal
-pyrazinamide/ethambutol 3x per week after meal
Continuation
- isoniazid/rifampin 3x per week after meals

37
Q

what is the effect of rifampin on HIV medications?

A

It will decrease levels

38
Q

How do you deal with decreased protease inhibitor levels in pts with HIV and TB?

A
  • replace rifampin with rifabutin
39
Q

How do you deal with decreased efavirenz levels in HIV pts with TB?

A

Increase the efavirenz dose

40
Q

How do you deal with decreased raltegravir levels in HIV pts with TB

A

double the raltegravir dose

41
Q

How does multi-drug resistant TB occur?

What is it defined as?

A
  • course of antibiotics in interrupted
  • levels of drug are insufficient to kill bacteria
  • defined as resistance to rifampin and isoniazid +/- other drug
42
Q

Which groups of pts does MDR-TB occur most easily?

A
  • pts with HIV

- immunosuppressant drugs

43
Q

What is the mortality rate of MDR-TB?

A

80%

44
Q

What is extensively-drug resistant TB defined as?

A
  • resistant to rifampin, isoniazid, any quinolon, any injectable 2nd line agent.
  • 25% of MDR-TB pts have this
  • makes TB essentially untreatable
45
Q

Describe the drug therapy used in MDR-TB

A
  • treated with a combo of 5-7 drugs
    isoniazide + rifampin + pyrazinamide + ethambutol + aminoglycoside + fluoroquinolone + (cycloserine/ethionamide/aminosalicyclic acid)
46
Q

How are the drugs administered for MDR-TB?

How long is therapy?

A
  • daily injectables for first 2-6 months
  • 3x/week injectables for 8 months
  • total therapy = 20 months
47
Q

How does bedaquiline work against TB?

A

it inhibits mycobacterium ATP synthase

potent against MDR-TB

48
Q

How is bedaquiline used in MDR-TB therapy?

A
  • used in combo with rifampin and pyrazinamide

- approved for use when other drugs are ineffective

49
Q

What are the side effects of bedaquiline?

A
  • liver toxicity
  • prolonged QT
  • chest pain
  • hemoptysis (coughing up blood)
  • nausea
  • headache

Pharmacology (5 decks)

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