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MOD1 > Antimycobacterial and Antifungal therapy > Flashcards

Antimycobacterial and Antifungal therapy Flashcards

1
Q

Resistance to any agent is present in ____ bacteria

A

1 x 10-5 to 1 x 10-8

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2
Q

Clinical rule for tuberculosis therapy (3)

A
  1. multiple drug therapy required
  2. start therapy with 3 or 4 drugs
  3. never change a single drug at a time
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3
Q

First line of therapy for tuberculosis: list the drug, it’s action, resistance if any, and adverse effects

A

“RIPE”

  1. Rifampin (rifabutin)
  • inhibts DNA-dependent RNA polymerase, prevention of chain initiation
  • drug turns bodily fluids red-orange tine
  • potent inducer of all CYP450 isoenzymes
  • heptatisis
  1. Izoniazid
  • inhibits mycolic acid biosynthesis
  • resistance in 1 x 10-6
  • hepatitis, peripheral neuropathy
  1. Pyrazinamide
    * mechanism unknown!
  2. Ethambutol
  • inhibits enzymes needed for cell wall synthesis
  • retrobulbar neuritis
  1. Streptomycin
  • an aminoglycoside
  • nephrotoxicity, neural toxicity
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4
Q

What additional vitamin is necessary to administer during first line TB therapy and why?

A

VB6, isoniazid can cause peripheral neuropathy

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5
Q

What is the standard active TB regimen?

A

INH + Vit B6, RIF, PZA, EMB x 2 months

then:

INH +Vit B6, RIF x 4

6 months total (4 for 2, 2 for 4!)

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6
Q

Resistance to one or more agents for TB therapy is common. What is the following resistances?

MDR = ?

XDR = ?

A

MDR = INH + Rifampin (1.5%)

XDR = INH + Rifampin + FQ and injectable agents

(^high mortality rate, very limited options for therapy)

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7
Q

Antimicrobial drugs for Hansen’s Disease

A
  1. Rifampin
  2. Dapson
  3. Clofazamine
  4. occasionally ofloxacin or MInocycline
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8
Q

What are the two antiinflammatory durgs for Hansen’s disease?

A
  1. Thalidomide
  2. Steroids
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9
Q

What are the 6 classes of antifungals?

A
  1. Polyenes
  2. Anti-metabolites
  3. Azoles
  4. Echinocandins
  5. Allylamines
  6. Others
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10
Q

List the steps to make ergosterol and the important enzymes involved. Which antifungal treatments block which steps?

A
  1. Mevalonic Acid –> Squalene
  2. Squalene –> Lanosterol (squalene epoxidase)
  3. Lanosterol –> Eergosterol (14 alpha demethylase)
  • allylamines block squalene epoxidase
  • echinocandins block 14 alpha demethylase
  • polyenes block ergosterol
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11
Q

List the two important Polyenes and their activity

A
  1. Amphotericin B
  2. Nystatin
  • most fungal pathogens
  • systemic candida
  • cryptococcal meningitis (with Flucytosine)
  • Severe pneumonia and extrapulmonary Balstomycosis, Histoplasmosis, and Coccidioiomycosis
  • Invasive Aspergillosis
  • Invasive Sportrichosis
  • Murcormycosis
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12
Q

What are adverse reactions to Polyenes?

A

“Amphoterrible, awfultericin”

  • febrile reactions (shake and bake)
  • Tubular nephrotoxicity (K, Mg+, and bicarbonate wasting)
  • glomerular nephrotocitity (increased creatinine)

“Nasty nystatin”

  • only effective against yeast
  • too toxic to take as iv, topical use only; not absorbed from GI so treats oral and esophageal infections
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13
Q

What are the two types of azoles?

A

Imidazoles and Triazoles

Imidazoles

  • ketoconazole
  • miconazole
  • clotrimazole

Triazoles

  • fluconazole
  • itraconazole
  • voriconazole
  • posaconazole
  • ravuconazole
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14
Q

Ketoconazole:

  1. activity
  2. characteristics
  3. clinical considerations
A
  1. Candida, Tinea
  2. Oldest, cheapest
  3. absoprtion highly gastric pH dependent– administer with food or cola; many cytochrome P450 effects, interacts with many meds
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15
Q

Clotrimazole:

  1. activity
  2. characteristic
A
  1. effective against yeasts and molds, skin and mucous membranes
  2. topical use only – cream, lotion, powder, solution; available OTC
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16
Q

Itraconazole:

  1. Activity
  2. clinical considerations
A
  1. histoplasmosis, Coccidiomycosis, Aspergillosis, Onychomycosis
  2. absorption highly gastric pH dependent–administer with food or cola
17
Q

Fluconazole:

  1. Activity
  2. Clinical considerations
A
  1. drug of choice for cryptococcus neoformans; effective against Candida
  2. Modest cytochrome effect
18
Q

What exception to the Candida specias is resistant to Fluconazole? What does Fluconazole also have little effect on?

A
  1. candida glabrata
  2. against filamentous fungi (aspergillus, zygomycetes/mucor)
19
Q

Voricanazole

  1. Activity
  2. Clinical considerations
A
  1. first line therapy for Aspergillosis, candida that is resistant to other triazoles
  2. unique toxicity: visual disturbance (30%), metabolized via cytochrome P450-multiple drug interactions
20
Q

Posiconazole:

  1. Activity
  2. Characteristic
A
  1. treats candida or aspergillus, prophylazie of fungal infections in cancer patients, improved activity against more resistant fungi (zygomycetes)
  2. oral formulation only
21
Q

Echinocandins irreversibly inhibits _____, which are responsible for _______

A

Beta-1,3-D glucan synthase; making glucan polymers, which provide cell wall rigidity

22
Q

Echinocandins:

  1. 3 main types
  2. activity
  3. characteristics
A
  1. Caspfungin, Micafungin, Anadulifungin
  2. Candida, Aspergillus (invasive), other unusual fungi (trichosporin, fusarium)
  3. iv therapy, generally well tolerated
23
Q

What is the one anti-metabolie?

  1. action
  2. activity
  3. clinical consideration

`

A

Flucytosine (5FC)

  1. interferes with DNA, RNA, and protein synthesis
  2. used in combo with other meds, especially cryptococcal meningitis
  3. bone marrow toxic
24
Q

Griseofulvan

  1. action
  2. activity
A

“greasy fulcrum”

  1. prevents cell division via funal cell mitotic spindles disruption
  2. levels dermatophyte plaques off skin; not used in USA due to high incidence of adverse reactions
25
Q

What is the one important Allylamine?

  1. action
  2. activity/uses
  3. clinical considerations
A

Terbinafine

  1. inhibits squalene epoxidase
  2. dermatomycoses, onychomycosis
  3. oral and topical use; high concentrations achieved in fatty tissue, skin, hair, nails
26
Q

Putting it all together: The two cutaneous diseases and treatments

A
  1. MOLD:
  • Imidazoles (ketoconazole, itraconazole, clotrimazole)
  • Terbinefine
  • Selsun Blue (selenium)
  1. YEAST (diaper rash, pannus infection)
    * Nystatin
27
Q

Putting it all together: treatment for Onychomycosis

A
  • Terbinafine
  • Itraconazole
28
Q

Putting it all together: Common treatment of Systemic Disease

Candida

A

Polyenes: YES (not C. lusitaniae)

Azoles: Most (not C. glabrata

Echinocandin: YES

29
Q

Putting it all together: Common treatment of Systemic Disease

Aspergillus

A

Polyenes: YES (esp invasive)

Azoles: Itraconazole, Voriconazole, Posiconazole

Echinocandin: YES (esp invasive)

30
Q

Putting it all together: Common treatment of Systemic Disease

Zygomycetes (Mucor)

A

Polyenes: VARIABLE

Azoles: posiconazole

Ehinocandin: NO

31
Q

Putting it all together: Common treatment of Systemic Disease

Cryptococcus

A

Polyenes: YES

Azoles: Fluconazole

Echinocandin: NO

32
Q

Putting it all together: Common treatment of Systemic Disease

Coccidioides

A

Polyenes: YES

Azoles: Fluconazole, Itraconazole

Echinocandin: some activity (limited data)

33
Q

Putting it all together: Common treatment of Systemic Disease

Blastomyces

A
  1. Polyenes: YES
  2. Azoles: Itraconazole
  3. Echinocandin: some activity (limited data)
34
Q

Putting it all together: Common treatment of Systemic Disease

Histoplasma

A
  1. Polyenes: YES
  2. Azoles: Itraconazole, Ketoconazole

Echinocandin: NO

35
Q

What are the three systemic diseases that Echinocandin does NOT work for?

A
  1. Zygomycetes (Mucor)
  2. Cryptococcus
  3. Histoplasma
36
Q

Which systemic disease do Polyenes have variable function?

A

Zygomycetes (Mucor)

MOD1 (9 decks)

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