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Antimicrobials > Anti-fungal & anti-protozoal drugs > Flashcards

Anti-fungal & anti-protozoal drugs Flashcards

1
Q

What are infections by fungi called?

A

Mycoses

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2
Q

Fungi are ____ with rigid cell walls composed largely of ___ rather than peptidoglycan

A

eukaryotes

chitin

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3
Q

What do fungal cell membranes contain?

A

Ergosterol (not cholesterol)

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4
Q

Name 2 polyenes antifungal

A
  1. Amphotericin B

2. Nystatin

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5
Q

Name the 2 categories of azole antifungals

A
  1. Triazole (fluconazole, itraconazole, voriconazole

2. Imidazole (clotrimazole, miconazole)

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6
Q

What are the systemic & subcutaneous antifungal drugs used?

A
  1. Amphotericin B
  2. 5-Flucytosine
  3. Echocandin (caspofungin, micafungin, anidulafungin)
  4. Triazoles (fluconazole, itraconazole, voriconazole)
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7
Q

What are the cutaneous antifungal drugs used?

A
  1. Imidazole (clotrimazole, miconazole)
  2. Nyastatin
  3. Terbinafine
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8
Q

What is the antiprotozoal agent used?

A

Metronidazole

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9
Q

What is the mechanism of action polyene antifungals?

A

bind to ergosterol in the plasma membranes of sensitive fungal cells to forms pores (channels). These pores disrupt membrane function, allowing electrolytes and other small molecules to leak from the cell, resulting in cell death.

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10
Q

How is amphotericin B commonly administered?

A

IV (poor oral bioavailability)

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11
Q

What advantage does the liposomal formulation of amphotericin B has over the conventional deoxycholate formulation?

A
  1. Liposomal formulation has reduced renal toxicity

2. better CSF penetration

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12
Q

What’s the consideration when using liposomal formulation of amphotericin B?

A

Cost

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13
Q

Name 2 clinical indications for amphotericin B

A

Broad spectrum

  1. Candidiasis
  2. Aspergillosis
  3. Cryptococcal meningitis (used with 5-flucytosine)
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14
Q

State 2 adverse effects associated with amphotericin B deoxycholate formulation

A
  1. Fever and chills (Infusion related toxicity)– “shake & bake syndrome”
  2. Nephrotoxicity
  3. Bone marrow suppression (like linezolid), ototoxicity
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15
Q

Name an anti-fungal, which is relatively safe for use in pregnancy despite systemic exposure.

A

Amphotericin B

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16
Q

What is the mechanism of action for 5-Flucytosine?

A

*5-flucytosine is converted,
by *cytosine deaminase,
to its metabolically active form *5-fluorouracil (5-FU), which inhibits *protein synthesis and inhibits *thymidylate synthase hence inhibiting DNA synthesis.

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17
Q

How is 5-Flucytosine commonly administered?

A

Oral (good oral bioavailability)

IV is available too

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18
Q

State at least 2 adverse effects associated with the use of 5 flucytosine

A
  1. Bone marrow suppression
  2. Hepatotoxicity
  3. GI related effects
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19
Q

State one clinical indication for 5-flucytosine

A
  1. Cryptococcal meningitis

(usually in combination with amphotericin B,
rarely used as single agent due to resistance + SYNERGISTIC increased penetrance due to pores)

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20
Q

Both amphotericin b & 5-flucytosine use should be adjusted in which group of patients?

A

Renal impairment

AmphB (low levels in urine for long time)

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21
Q

Name 3 echinocandins

A
  1. Caspofungin
  2. Micafungin
  3. Anidulafungin
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22
Q

State the mechanism of action of the echinocandins

A

Echinocandins inhibit the activity of the glucan synthase complex, resulting in loss of the structural integrity of the cell wall.

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23
Q

How are echinocandins commonly administered?

A

Intravenously (poor oral bioavailability)

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24
Q

Name 2 fungal species against which Echinocandins have potent activity

A
  1. Candida (first line)

2. Aspergillus (second line: 1st line voriconazole then amphotericin b)

25
Q

What is the mechanism of action of azoles?

A

inhibit C-14 α-demethylase (CYP450 enzyme),
thereby blocking the demethylation of lanosterol to ergosterol.
This inhibition of ergosterol biosynthesis disrupts membrane structure and function and inhibits fungal cell growth.

26
Q

Do the triazoles have good oral bioavailability?

A

Yes

27
Q

Use of triazole

A

systemic *tx or *prophylaxis

for cutaneous/systemic fungal infections

28
Q

State 3 adverse effects common to the triazoles

A
  1. QT prolongation
  2. Hepatotoxicity
  3. GI side effects
29
Q

Name a triazole which is associated with the adverse effect of cardiotoxicity

A

Itraconazole

30
Q

Name a triazole which is associated with the adverse effect of neurotoxicity (visual disturbances/hallucinations)

A

Voriconazole

31
Q

What’s the first line tx for invasive aspergillosis?

A

Voriconazole

32
Q

Name one class of anti-fungals, which is significantly associated with CYP450 enzymes related drug-drug interactions?

A

Azoles
(Other non anti-fungal agents include macrolides, HIV protease inhibitors, rifampicin, which all have either significant CYP450 inhibitory or inducing activity)

Antibiotics like fluoroquinolones and tetracyclines does have some DDI too)

33
Q

Which azole should not be taken with antacids?

A

Itraconazole (low pH improves absorption)

34
Q

Indications for fluconazole

A
  1. Cryptococcal meningitis (but first line: amphotericin b + 5-flucytosine)
  2. good CSF penetrance- most fungal meningitis
35
Q

Indications for itraconazole

A

Broad spectrum compared to fluconazole

  1. Onychomycosis (non-imm compromised)
  2. Oral solution- esopha & oropharyngeal candidiasis
36
Q

Dosage forms of itraconazole

A

Oral capsules- taken full meal increased absorption w acidic pH

Oral solution - empty stomach

37
Q

How are the imidazoles commonly administered?

A

Topical (minimally absorbed)

38
Q

Adverse effect of topical imidazole use

A
  1. Contact dermatitis
  2. Vulvular irritation
  3. Edema
39
Q

Name 2 anti-fungal drugs that can be used in the management of vuvlovaginal candidiasis and describe how it is administered

A
  1. clotrimazole (cream)
  2. fluconazole (single dose oral)
  3. miconazole (vaginal suppository)
  4. nystatin (vaginal suppository)
40
Q

Indications for topical clotrimazole

A
  1. dermatophyte infections
  2. vulvovaginal candidiasis
  3. oral thrush (dm/hiv/dentures)
41
Q

Is nystatin administered parenterally?

A

No, oral suspension/tablets, cream, pessary

42
Q

State a clinical indication for nystatin, and how it is administered.

A
  1. oropharyngeal candidiasis (oral agent; swish and swallow or swish and spit)
  2. vulvovaginal candidiasis (vaginal suppository)
43
Q

What is terbinafine’s mechanism of action?

A

inhibits squalene epoxidase, thereby blocking its conversion to lanosterol and biosynthesis of ergosterol, an essential component of the fungal cell membrane.

44
Q

How is terbinafine administered for the management of tinea capitis?

A

Oral against trichophyton causing tinea

(Topical application cannot be used for the management of tinea capitis)

45
Q 
Which of the following option(s) is/are least suited for a fungal meningeal infections?
A. Amphotericin B
B. 5-Flucytosine
C. Echinocandins
D. Fluconazole
E Itraconazole
F.Voriconazole
A

Echinocandins and Itraconazole have poor CSF penetration.

46
Q

What are some of the anti-fungal agents used in the treatment or onychomycosis?

A

Itraconazole - oral

Terbinafine - oral

47
Q

In pregnancy, what route of administration is preferred for terbinafine?

A

Vaginal (little ab as topical)

48
Q

What’s the drug used as an anti-protozoal agent?

A

Metronidazole

49
Q

Where are protozoal infections common?

A

Underdeveloped tropical/subtropical countries

50
Q

Can most anti-protozoal agents be used during pregnancy?

A

No

51
Q

What cell type is protozoal?

A

unicellular eukaryotes

52
Q

What is amebiasis caused by?

A

Entamoeba histolytica

53
Q

Chemotherapy for amebiasis -routes of administration

A
  1. Luminal- in int. lumen
  2. Systemic- intestinal wall & liver
  3. Mixed
54
Q

MOA of metronidazole

A 
nitro group of metronidazole 
electron acceptor
forms reduced cytotoxic free radicals
protein & DNA damage
death of Entamoeba histolytica trophozoites

more so for anaerobic org

55
Q

Indications for metronidazole

A
  1. Amebic infections- E. histolytica, trichomonas vaginalis, Giardia lamblia
  2. Anaerobes- Bacteroides spp, clostridium difficile
  3. H pylori
56
Q

Does metronidazole penetrate CSF?

A

Yes very well

57
Q

Which patients should metronidazole be dose adjusted for?

A

Hepatic (metabolism) & renal (elimination) impairements pt

58
Q

Name at least 2 side effects for metronidazole

A
  1. Metallic taste

2. Oral moniliasis (yeast infection in mouth)

59
Q

If pregnant pt has amebic infection, would you give metronidazole?

A

No unless clearly needed

Antimicrobials (11 decks)

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