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PHRM 840 > Anti-Mycobacterial Agents > Flashcards

Anti-Mycobacterial Agents Flashcards

1
Q

Mycobacterium tuberculosis-Mtb causes

A

TB

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2
Q

Mycobacterium leprae causes

A

leprosy

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3
Q 
Slow-growing, slender, rod-
shaped aerobic bacteria with a unique
lipid-rich (waxy, acid-fast)) cell wall.
May remain dormant in the host for
long periods.
A

Mycobacterium tuberculosis

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4
Q

Mycobacterium tuberculosis is transmitted by

A

inhalation of airborne droplets that can remain aloft for minutes to hours

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5
Q

Why are antimicrobials for TB treatment combined?

A

To decrease emergence of resistant strains.

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6
Q

TB bacteria can become active if

A

immune system

doesn’t prevent growth

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7
Q

Latent TB infection

A

Exposure to bacteria, but bacteria become inactive

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8
Q

Latent TB symptoms

A

no symptoms or physical findings suggestive of TB

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9
Q

In LTBI, respiratory smear and culture are

A

negative

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10
Q

Symptoms of pulmonary TB disease

A

fever,cough, nightsweats,weight loss,fatigue,hemoptysis,
decreasedappetite

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11
Q

Pulmonary TB disease respiratory specimens and culture are

A

positive

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12
Q

5 Principles of Active TB Treatment

A
  1. Multiple drugs MUST be used.
  2. Drug sensitivity testing is mandatory.
  3. Single daily dosing of drugs is preferred.
  4. Prolonged therapy is necessary (generally >6 months).
  5. Monitoring for patient compliance and toxicity is
    required (DOT, Directly observed therapy or VOT, Video
    Observed Treatmen
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13
Q

First line agents for TB

A

Rifamycins: Rifampin (RIF), Rifabutin, Rifapentine
Isoniazid (INH)
Pyrazinamide (PZA) Ethambutol (EMB)

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14
Q

Second line agents for TB

A 
Streptomycin 
Amikacin 
Quinolones
(Moxifloxacin) 
Cycloserine 
P-Aminosalicyclic Acid Ethionamide
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15
Q

Second line drugs used for TB treatment considered if

A

a) Resistance to first-line agents
b) Clinical failure of first-line therapy
c) Serious adverse drug reactions that limit treatment

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16
Q

Initiation phase treatment of TB

A

isoniazid, rifampin, pyrazinamide and ethambutol

(the 4 first –line agents) administered for 2 months.

17
Q

Continuation phase treatment of TB

A

At two months, treatment with isoniazid and rifampin
are continued for 4 months - or 7 months w/ the
following:
• cavitation on chest X-ray
• positive acid fast bacillus smear
• positive culture

18
Q

What inhibits synthesis of mycolic acids

A

Isoniazid (INH)

19
Q

What is a pro-drug activated inside the mycobacterium

A

Isoniazid (INH)

20
Q

Isoniazid (INH) resistance

A

Mutations in katG or inhA promoter region (increased expression)

21
Q

Isoniazid is metabolized in

A

liver by acetylation

22
Q

Isoniazid ADME

A

-Oral absorption
-Aluminum containing antacids can interfere with absorption
(take on empty stomach, 2 hours from taking antacids)
- penetrates CSF

23
Q

Isoniazid is hepatotoxic so monitor

A

for signs of hepatic dysfunction/ hepatitis (LFTs)

24
Q

inhibits mycobacterial cell wall synthesis but primarily enhances activity of lipophilic drugs

A

Ethambutol (Myambutol®

25
Q

Ethambutol (Myambutol® ADME

A

-Oral absorption
-Aluminum containing antacids can
interfere with absorption
-Hepatic metabolism

26
Q

most important toxicity associated with use of Ethambutol

A

Optic neuritis

27
Q
  • The pro-drug enters M. tuberculosis by passive diffusion
  • Converted to pyrazinoic acid (POA) by nicotinamidase/pyrazinamidase (PZase).
  • Disrupts intracellular pH and membrane transport (may effect metabolism- energy production…exact MOA unresolved)
A

Pyrazinamid

28
Q

Pyrazinamid ADME

A
  • Well absorbed
  • Wide tissue distribution, CSF
  • Hepatic metabolism
29
Q

Pyrazinamid ADE

A

-Liver injury (15%) with jaundice (2-3%),
rarely fatal
-Do not use with decreased liver function
-Monitoring: LFTs

30
Q

Binds to the β-subunit of bacterial DNA-dependent RNA polymerase. Inhibits RNA synthesis

A

Rifamycins (Rifampin, Rifabutin, Rifapentine)

31
Q

Use Rifabutin instead of Rifampin in

A

HIV patients on ART therapy (to avoid drug interactions)

32
Q

causes orange staining of host secretions

A

Rifampin

33
Q

Rifampin ADME

A
  • Oral administration (food/antacids decrease absorption)
  • Distributes to all body fluids and organs, including CNS
  • Induces hepatic mixed-function oxidases increasing its own metabolism as well as other drugs. (i.e. oral contraceptives)
  • Eliminated via feces and urine
34
Q

TB that is resistant to
at least two of the best anti-TB drugs, isoniazid and
rifampicin

A

Multidrug-resistant TB (MDR TB)

35
Q

relatively
rare type of MDR TB. XDR TB is defined as TB that is
resistant to isoniazid and rifampin, plus resistant to any
fluoroquinolone and at least one of three injectable
second-line drugs (i.e., amikacin, kanamycin, or
capreomycin)

A

Extensively drug-resistant TB (XDR TB)

36
Q

Inhibits proton pump for mycobacterial ATP

synthase

A

Bedaquiline (Sirturo®)

37
Q

approved for combination use against XDR TB

A

Pretomanid

PHRM 840 (9 decks)

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