Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology (Topic C) > C2. Antimycobacterial drugs > Flashcards

C2. Antimycobacterial drugs Flashcards

1
Q

What are Mycobacteria?

A
  1. Mycobacteria are slow-growing aerobic, non-motile rods with a resistant lipid-rich wall.
  2. They are facultative intracellular pathogens and can remain dormant.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

List the 1st line anti-TB medications.

A

“RIPE” Drugs:

  1. Rifampin (RA)
  2. Isoniazide (INH)
  3. Pyrazinamide (PZA)
  4. Ethambutol (ETB)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List the 2nd line anti-TBC meds.

A
  1. Ethionamide
  2. Cycloserine
  3. PAS (para-aminosalicylic acid)
  4. Kanamycin/Amikacin
  5. Capreomycin
  6. Fluoroquinolones
  7. Rifabutin
  8. Linzolid
  9. Bedaquiline
  10. Delamanid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List the anti-leprosy meds.

A
  1. Dapsone
  2. Rifampin
  3. Clofazemine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the agents used to treat Mycobacterium Avium Complex (MAC) infection.

A

Mneumonic: “AIDS”

  1. Azithromycin
  2. Claritromycine
  3. Ethambutol
  4. (+/-) Rifabutin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How long do you give First-Line Agents?

A

You give all 4 for first 2 months then just Rifampin (RA) and Isoniazide (INH) for 4 more months after that.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What considerations should you make regarding the Drug Distribution of the anti-TB medications?**

A
  1. In younger, well-vascularized, cellular granulomas → anti-TBC drugs must enter interstitium and penetrate immune cells to enter phagolysosomes where bacteria are In necrotic granulomas / cavities → drugs must diffuse through the caseated material to reach extracellular pathogens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the MOA of Nitrofurantoin?

A

Nitrofurantoin concentrates in urine and is reduced inside bacteria by flavoproteins → highly reactive intermediates → cause damage to ribosomes, DNA and metabolic processes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the MOA of Bacitracin?

A

Bactracin is used topically and it inhibits a carrier for transfer of peptidoglycan subunits → disrupts cell wall synth of the bacteria.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the MOA of Phosphomycin?

A

Phosphomycin is administered as prodrug called trometamol. It inhibits the formation of N-acetyl muramic acid → cell wall synth disruption.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the MOA of Colistin?

A

Colistin also known as polymyxin E is a cationic detergent → membrane disruption.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is Mycobacterium Avium Complex (MAC)?**

A
  1. Common in systemic disease in AIDs patients with CD count <50 can use azithromycin/clarithromycin with ethambutol +/- rifabutin
  2. Mycobacterium avium complex is a group of mycobacteria comprising Mycobacterium intracellulare and Mycobacterium avium (No mention of M. chimera in ref) that are commonly grouped together because they infect humans together; this group, in turn, is part of the group of nontuberculous mycobacteria. These bacteria cause disease in humans called Mycobacterium avium-intracellulare infection or Mycobacterium avium complex infection.[2]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the MOA of Dapsone?

A

Dapsone inhibits folate synthesis used in combo with rifampin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is Clofazimine used for?

A

It is used for lepromatous form of leprosy with ‘leonine facies’, from Sketchy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the MOA of Rifampin?

A

Rifampin inhibits RNA polymerase → bactericidal effect, especially dormant microbes with a long post-antibiotic effect (PAE).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the MOA of Linezolid?

A

Linzolid inhibits protein synthesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

When is Rifabutin used?

A
  1. Rifabutin is similar to rifampin, but less enzyme induction.
  2. Its used to replace rifampin when treating TBC in HIV patients, due to less interaction with antiretroviral protease inhibitors.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

List the Fluoroquinolones.

A
  1. ciprofloxacin
  2. levofloxacin
  3. gatifloxacin
  4. moxifloxacin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the MOA of Capreomycin and what is it used for?

A

Capreomycin acts by protein synthesis inhibition and its used for multiresistant M. tuberculosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the indications for Kanamycin / Amikacin?

A

They are used in case of streptomycin resistance / multiresistance.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the MOA of Para-aminosalicylic Acid (PAS)?

A

It inhibits folate synthesis as an analog of PABA → bacteriostatic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the MOA of Cycloserine?

A

Cycloserine is a D-Ala analog → inhibits Ala racemase + thus cell wall synthesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the MOA of Ethionamide?

A

It is related to isoniazid and also inhibits mycolic acid synth.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the indications of Second-Line TB Agents?

A

Indicated in resistance to first-line agents or to limit adverse reactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the MOA of Isoniazid?

A
  1. The active metabolites block of isoniazid mycolic acid synth via enzyme/carrier protein inhibition.
  2. bactericidal in actively growing microbes,
  3. -static in dormant Mycobacterium
  4. specific catalase G enzymes create active metabolites within the microbes.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the MOA of Pyrazinamide?

A

Pyrazinamide is a prodrug is converted to activated pyrazinoic acid by mycobacterial pyrazinamidase. The mechanism itself is unknown. It does however seem to cause membrane/metabolism disruption and therefore results in a bactericidal effect, esp. in dormant Mycobacteria. Resistance does develop fast by pyrazinamidase mutations. This drug is not given by itself but in combo with the other “RIPE” drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the MOA of Streptomycin?

A
  1. Also a “first-line” anti-TB drug, but not part of the classic combination
  2. Active against M. tuberculosis (no Kansasii or Avium) in open caverns / bronchi only since aminoglycosides require O2 to enter cells
28
Q

What is the MOA of Ethambutol?

A
  1. It inhibits arabinogalactan formation by blocking arabinosyl transferases.
  2. Has a bacteriostatic effect.
29
Q

What spectrum does Nitrofurantoin cover?

A

It has good activity against:

  1. Staph
  2. Strep
  3. Enterococcus
  4. E. coli.
30
Q

What are the side effects of Nitrofurantoin?

A
  1. Nausea
  2. Headache
  3. Flatulence more rarely
  4. Pulmonary hypersensitivity reactions
  5. Skin reactions (itching, urticaria, hair loss)
31
Q

What are the indications of Nitrofurantoin?

A

UTI

32
Q

What spectrum does Bacitracin cover?

A

Mainly covers Gram+.

33
Q

What are the side effects of Bacitracin?

A
  1. High nephrotoxicity → local topical use only
34
Q

What are the indications for Bacitracin?

A

Mixed skin infections.

35
Q

What spectrum does Phosphomycin cover?

A

Gram + (Staph) and Gram - (E. coli, Klebs, Enterobacter, Proteus) bacteria.

36
Q

What are the kinetics like for phosphomycin? **

A
  1. Only therapeutic in urine
  2. Safe in pregnancy!
  3. Well absorbed from the GI and widely distributed, including tuberculous meningitis.
37
Q

What spectrum does Colistin cover?

A
  1. Colistin covers a narrow spectrum
  2. Only Gram - aerobe (GI rods), but Proteus, Serratia are resistant. Pseudomonas + Acinetobacter are highly susceptible.
38
Q

What are the side effects of Colistin?

A

Highly toxic → nephro- and peripheral neurotoxic (no CNS entry)

39
Q

What are the indications for Colistin?

A
  1. Severe multi-resistant infections (eg, multi-resistant Acinetobacter)
  2. UTI
  3. cystitis (as local wash)
40
Q

What are the side effects of Dapsone?

A

It is generally well-tolerated, but can cause hemolysis in G6PD deficiency (showing “bite cells” with Heinz bodies) (also may cause agranulocytosis)

41
Q

What spectrum does Rifampin cover?

A
  1. Most Mycobacteria (incl. leprae) plus N. meningitidis and H. flu (as prophylactic monotherapy), and Pox viruses.
  2. Good for highly resistant Staph endocarditis/osteomyelitis with ciprofloxacin.
42
Q

What are the pharmacokinetics like for Rifampin?

A
  1. good oral absorption + distribution (phagocytes, abscess/cavity, CSF)
  2. accelerates its own hepatic metabolism (CYP inducer, incl. 3A4)
  3. hepatic and renal elimination.
43
Q

What are the side effects of Rifampin?

A
  1. Hepatotoxicity - ↑ enzymes, rarely hepatitis
  2. Orange Discoloration - urine, sweat, tears (rare neuro issues)
44
Q

What spectrum does Linzolid cover?

A

Linzolids are used for multiresistant / atypical Mycobacteria.

45
Q

What are the Pharmacokinetics like for Linzolid?

A

Given orally long-term therapy

46
Q

What are the possible side effects of Linzolid therapy?

A
  1. Bone marrow suppression
  2. Neuropathy.
47
Q

What are the side effects of Kanamycin/Amikacin?

A

It is nephro-/ototoxic.

48
Q

What is the route of administration for Kanamycin/Amikacin?

A

They are given parenterally.

49
Q

What are the indications for PAS?

A

PAS is good for M. tuberculosis, with little resistance.

50
Q

What are the pharmacokinetics like for PAS?

A
  1. Oral absorption
  2. Good distribution
  3. Metabolized by acetylation
51
Q

What are the side effects of PAS?

A
  1. GI effects (ulcer, nausea, D)
  2. CNS effects
  3. Hypersensitivity
52
Q

How is the pharmacokinetics like for Cycloserine?

A
  1. Oral absorption
  2. CNS penetration
  3. Partial metabolism
53
Q

What are the indications for Cycloserine?

A

Cycloserine is good for INH / streptomycin-resistant M. tuberculosis (plus many G+/- but only used for TBC).

54
Q

What spectrum does Ethionamide cover?

A

Ethionamide is good for M. tuberculosis, kansasii and avium.

55
Q

How is the pharmacokinetics like for Isoniazide?

A
  1. Isoniazide is a pro-drug given orally
  2. Distributes well, even in CSF and granulomas metabolized in liver by acetylation + eliminated in urine.
56
Q

What spectrum does Pyrazinamide cover?

A

Only for M. tuberculosis good substitute for INH in case of resistance.

57
Q

How does the pharmacokinetic of Streptomycin look like?

A
  1. Only parenteral via IM 2-3x/wk.
  2. It does not enter the CNS.
58
Q

What spectrum does Ethambutol cover?

A

M. tuberculosis, kansasii and some avium.

59
Q

What are the side effects of Cycloserine administration?

A
  1. Severe CNS effects: tremor, acute psychosis, seizure
  2. Peripheral neuropathy
60
Q

What are the side effects of Ethionamide?

A
  1. can be hepatotoxic
  2. GI side effects
  3. allergy
61
Q

How are the pharmacokinetics like for Ethionamide?

A
  1. absorbed orally
  2. enters CNS
  3. metabolized by liver + excreted in urine.
62
Q

What are the side effects of Isoniazide?

A
  1. Hepatotoxic: worse w/ alcohol or rapid acetylators
  2. Peripheral Neuropathy: paresthesias (sometimes CNS effects: headache, memory loss, seizure) via B6 deficiency caused by INH-pyridoxine binding worse in slow acetylators + reversible with B6 supplementation.
  3. Muscle cramps, fever, rash (Drug-Induced Lupus, anion-gap acidosis and CYP450 inhibition)
63
Q

How are the Pharmocokinetics like for Pyrazinamide?

A
  1. Good oral absorption and good distribution (penetrates BBB).
  2. Liver metabolism and urine excretion.
64
Q

What are the side effects of Streptomycin?

A
  1. Nephrotoxic
  2. Ototoxic
65
Q

What are the side effects of Ethambutol?

A
  1. Retrobulbar Neuritis: ↓ visual acuity, red-green color blindness and scotomas (check vision monthly)
  2. Rarely nausea, joint pain, headache and allergy
66
Q

How do the pharmacokinetics of Ethambutol look like?

A
  1. Good oral absorption (but ↓ by alcohol) and macrophage penetration / CNS
  2. Excreted unchanged in urine
67
Q

What are the side effects of Pyrazinamide?

A
  1. Hepatotoxicity: as severe as liver necrosis
  2. Hyperuricemia: can precipitate gout attacks; but rifampin ↓ uric acid!

Pharmacology (Topic C) (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions