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Infectious Disease > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Different mechanisms of antifungals?

A
  1. alter cell membrane permeability
  2. block nucleic acid synthesis
  3. disrupt microtubule functions
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2
Q

Antifungals that alter cell membrane permeability?

A

Azoles (ketoconazole), polyenes (Nystatin), Terbinafine

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3
Q

Antifungals that block nucleic acid synthesis?

A

Flucytosine

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4
Q

Antifungals that disrupt microtubule functions?

A

Griseofulvin

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5
Q

What topical drugs are used for cutaneous fungal infections?

A

azoles and polyenes

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6
Q

What are the systemic drugs used for superficial fungal infections?

A

Griseofulvin, Terbinafine, and Itraconazole (azole)

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7
Q

Systemic drugs used for systemic fungal infections?

*Bad systemic infections

A

Amphoteracin B (Amphoterrible -> don’t use)
Azoles
Flucytosine (5-FC)

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8
Q

What are the topical azalea antifungals and their MOA?

A

clotrimazole, ketoconazole, miconazole

  • fungicidal, impairs the formation of fungal cell membranes therefore increasing permeability (so intracellular contents leak out leading to cell death)
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9
Q

Clinical uses of Topical azole antifungals

A

tinea corporis (body), tinea cruris (jock itch), tinea pedis (athletes foot), cutaneous candidiasis (yeast infection)

*Tinea=condition caused by dermatophytes

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10
Q

CIs of topical azole antifungals (c,k,m)

A

pregnancy, lactation

  • caution w/ liver failure
  • don’t use ketoconazole if hx of sulfa allergy
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11
Q

Application of topical azole antifungals

A

lotion or powder ->
apply 2x daily for 2-4 weeks
continue for 1 week after lesions clear

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12
Q

MOA of topical azole antifungals

A

inhibit CYP450, inhibit synthesis of ergosterol (cell membrane of fungi)

SE: pruritis, irritation, burning or stinging

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13
Q

Clotrimazole

A

Names: Gyne-Lotrimin, Mycelex 3&7, Trivagizole 3

Indications:

  • cutaneous candidiasis (topical)
  • vulvovaginal candidiasis (topical)
  • oropharyngeal candidiasis (thrush -> oral formulation)

CI: hypersensitivity to clotrimazole or any other component of formula

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14
Q

Oropharyngeal candidiasis dosing

A

troche dissolved slowly 5x / day for 14 days

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15
Q

Clotrimazole MOA

A

binds to phospholipids in the fungal cell membrane altering permeability and loss of intracellular elements

  • very little systemic absorption from topical
  • oral: inhibitory concentrations in saliva for up to 3 hours post dissolution of troche
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16
Q

Drug interactions for clotrimazole

A

topical= none

oral drug interactions similar to other azaleas due to inhibition of P450 enzymes

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17
Q

Adverse effects of Clotrimazole

A

Topical: vulvovaginal burning

oral: abn. LFTs, pruritus, N/V
monitor: periodic LFTs

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18
Q

Ketoconazole (topical)

A

formula: cream, foam, gel or shampoo
indications: tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis, + seborrheic dermatitis and tinea versicolor

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19
Q

Topical azoles: miconazole (micatin, monistat, desenx, lotrimin AF)

A

formulations: aerosol, powder aerosol, intravaginal supp, cream, ointment, lotion

indications: tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis, tinea versicolor + vulvovaginal candidiasis
- intravaginal sups may interfere with warfarin

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20
Q

Topical Polyene: Nystatin (mycostatin)

A

Indications: cutaneous and mucocutaneous infections caused by candida
-oral and intestinal candidia infections
CIs: hypersensitivity reaction

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21
Q

Mycostatin MOA

A

binds to sterols in fungal cell membrane and changes the cell wall permeability leading to the leakage of intracellular contents

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22
Q

Mycostatin dosing

A

cream, ointment and powder:100,000 U/g 2-3x daily

oral suspension - 400,000-600000 U QID

intestinal infections: tablets- 500000-1,000,000 U po q8H

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23
Q

Mycostatin pharmokinetics/dynamics

A

onset of action -> relief of sxs: w/in 24-72 hours
systemic absorption- none (why its used to tx intestinal infections)
-no drug interactions

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24
Q

Adverse effects of mycostatin

A

contact dermatitis - develop blisters

  • SJS
  • oral: N/V/D
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25
Q

Systemic drugs for superficial fungal infections

A

Griseofulvin, terbinafine, itraconazole

-for hair, skin and nails

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26
Q

Griseofulvin indications

A

used to tx tine infections of skin, hair and nails

-most commonly used for tx of tine capitis (scalp)

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27
Q

Griseofulvin MOA

A

inhibits fungal cell division
binds to himan keratin making it resistant to fungal invasion (goes down into hair follicles as hair grows out, takes a long time to work)

28
Q

Duration fo Griseofulvin therapy

A 
tinea corporis: 2-4 weeks
tinea cruris: 2-6 weeks
tinea capitis: 4-6 weeks
tinea pedis: 4-8 weeks
tinea unguium (nails): 4-6 months or longer

administration: fatty meal (PB or ice cream) may increase GI absorption
- with food or milk to decrease GI upset

29
Q

CIs and precautions with administration of Griseofulvin

A
  • liver failure
  • porphyria (porphyrin accum)
  • preg (X)
  • caution if hx of pcn allergy
  • breast feeding not recom.
30
Q

What periodic monitoring is required if pt is on long term tx of griseofulvin

A

renal fxn, liver fxn, and CBC to watch for granulocytopenia

* get CBC and CMP

31
Q

Drug interactions of Griseofulvin

A

many due to its effects on CYP1A2, CYP2C9, CYP3A4

-warfarin, oral contraceptives, alcohol, barbiturates, cyclosporine and others

32
Q

Adverse reactions of griseofulvin

A

photosensitivity, SJS, toxic epidermal necrolysis, erythema multiforme, jaundice, elevated LFTs, granulocytopenia, dizziness, fatigue, HA, N/V/D, drug induced lupus like syndrome

33
Q

Dose adjustments of griseofulvin dependent on?

A

smaller particle size the greater bioavailability requiring dose adjustments between 2 formulations
- microsize: suspensions, grifulvin V tablets
-ultramicrosize: Gris-PEG tablets
(tablets are spendy)!

34
Q

Terbinafine (Lamisil)

A

oral/systemic formula:

  • oncychomycosis of toenails and fingernails
  • tinea capitis

CIs: Hypersensitivity

35
Q

Terbinafine MOA

A

creates ergosterol deficiency within the cell wall leading to cell death

36
Q

Dosing of Terbinafine

A

oral: onychomcosis of the fingernails -> 250 mg/day x 6 weeks

oncychomycosis of the toenails: 250 mg day x 12 weeks

37
Q

Terbinafine pharmacodynamics/kinetics

A

effective half life 36 h

  • distribution to the sebum and skin
  • 99% plasma bound (drug interactions)
  • hepatic metabolism
38
Q

drug interactions of Terbinafine

A

due to inhibition of CYP450 enzymes there are some sig. drug interactions including metoprolol (B blocker), and tramadol - pain med (oral formulation)

39
Q

Terbinafine SEs

A

HA, diarrhea, LFTs,

burning, contact dermatitis, dryness, pruritus, rash

40
Q

Itraconazole (sporanox) indications for superficial infections

A

**Onychomycosis

41
Q

Itraconazole (sporanox) CIs

A

hypersensitivity to intraconazole or other azoles

  • concurrent administration with other drugs that act at CYP450 system
  • Ventricular dysfunction (negative inotrope)
  • CHF
  • pregnancy or intend to become pregnant
42
Q

Itraconazole (Sporanox) Pharmacodynamics/Kinetics

A

requires gastric acidity for optimal absorption

  • better absorbed with food (capsule)
  • solution better absorbed on an empty stomach
  • 99.*% protein bound
  • half life: 21 hours
  • metabolized by liver
43
Q

Itraconazole (Sporanox) drug interactions

A

significant list of drug interactions:

  • proton pump inhibitors, anxiolytics, pain meds, antiplatelet agents, anthypertensives, cholesterol lowering meds
  • drug interaction checker is a must when using these drugs
44
Q

Itraconazole (sporanox) adverse effects

A

Nausea, diarrhea, edema (from L. ventricular dysfunction), HA, rash, Abnorm. LFTs, heart failure, arrhythmia, hearing loss, and many more

45
Q

Itraconazole (sporanox) monitoring

A

baseline LFTs, monthly LFTs (if long term therapy), serum concentrations to assure therapeutic levels (obtain after 2 weeks of therapy, draw anytime during the dosing interval)

46
Q

Systemic drugs for systemic fungal infections (the worst of the worst)

A 
Amphoteracin B (stay away from),
azoles: ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, flucytosine (5-FC)
47
Q

Amphoteracin B (Amphoterrible!!)

A

systemic antifungal for use in SEVERE fungal infections

  • IV only
    indications: severe systemic and CNS infections that are progressive and potentially life threatening.

SEs: anaphylaxis, infusion reaction, leukoencephalopathy (damage to brain white matter), nephrotoxicity

48
Q

Amphotericin B MOA

A

bind to ergosterol and alters cell membrane permeability and may also stimulate the macrophages

monitor: renal and liver fxn (CMP), electrolytes, PT/PTT, CBC

49
Q

Drug interactions with Amphotericin B

A

aminoglycosides, antifungal agents, corticosteroids, cyclosporine

50
Q

Itraconazole (Sporanox) indications - for systemic infections

A

(for superficial -> onychomycosis)
systemic: aspergillosis, blastomycosis, esophageal and oropharyngeal candidiasis (oral soln), coccidioidomycosis, histoplasmosis

51
Q

Itraconazole (sporanox) CIs

A

hypersensitivity to intraconazole or other azoles

  • concurrent admin with other drugs that act at CYP450 system
  • ventricular dysfunction (negative inotrope)
  • CHF
  • pregnancy or intend to become pregnant
52
Q

Itraconazole (sporanox) pharmodynamics/kinetics

A

requires gastric acidity for optimal absorption

  • better absorbed with food (capsule) but soln is better absorbed on an empty stomach,
  • 99.8% protein bound, half life: 21 hours
  • metabolized by the liver
53
Q

Itraconazole (Sporanox) drug interactions

A

sig. list of drug interactions
- proton pump inhibitors, anxiolytics, pain meds, antiplatelet agents, antihypertensives, cholesterol lowering meds
- drug interaction checker is a must when using these drugs (same as for topical infections -same drug)

54
Q

Itraconazole (sporanox) adverse effects (for systemic use)

A

Nausea, diarrhea, edema, HA, rash, Abnorm. LFTs, Heart failure, arrhythmia, hearing loss, and many others

55
Q

Itraconazole (sporanox) monitoring

A

Baseline LFTs, monthly LFTs (if long term therapy), serum concentrations to assure therapeutic levels: obtain after 2 weeks of therapy, draw anytime during dose interval

56
Q

Fluconazole (diflucan) indications

A
  • Blastomycosis (CNS disease)
  • candidiasis: candidemia, endocarditis, orpharyngeal, prophylaxis, vaginal and more
  • coccidioidomycosis: meningitis, pneumonia, prophylaxis
  • crypococcosis: meningitis, pneumonia
57
Q

Fluconazole (Duflucan) CIs

A

hypersensitivity to fluconazole or other azaleas

-coadmin. of CYP3A4 substrates which may lead to QT prolongation (cisapride, primozide, or quinidine)

58
Q

FLuconazole (Diflucan) route and dose

A

IV and oral

dose dep. in disease process

59
Q

Fluconazole (diflucan) pharmacokinetics/dynamics

A

distribution: widely thoughout the body, good penetrate into CSF, eye, peritoneal fluid, sputum, skin and urine,

protein binding: 11-12% in plasma
Half life:w/ normal renal function about 30 hours

60
Q

Fluconazole (Diflucan) Drug interactions

A 
Extensive list:
Most commonly used drugs that fluconazole interacts with:
-statins (cholesterol)
- sildenafil (viagra)
-warfarin
-sulfonylureas (antidiabetic meds)
- proton pump inhibitors
-Ca channel blockers, B blockers (antiHTNs)
-Diclofenac (NSAID)
-Fentanyl, benzodiazepines
-macrolides
61
Q

Fluconazole (Diflucan) Adverse effects

A 
pregnancy: C/D
HA, dizziness
N/V/D
elev LFTs
QT prolongation
62
Q

Fluconazole (Diflucan) monitoring

A

Baseline LFTs

periodic LF, RF and K

63
Q

Systemic ketoconazole (Nizoral) FDA warning

A

Rare cases of serious hepatotoxicity including hepatic failure and death associated with ketoconazole. Occurred in pts receiving high doses for short tx durations and in pts receiving low doses for long durations

  • risk of decreased adrenal corticosteroid secretion at doses >/= 400 mg/day
  • risk of QT prolong. if on other drugs known to prolong QT
  • significant inhibitor of CYP450 enzymes: statins,, Ca channel blockers, antidepressants, macrocodes, and b-blockers
64
Q

Ketoconazole indications (oral) for systemic infections

A

use restricted only for tx of systemic life threatening fungal infections when other safer agents cannot be used:
-blastomycosis, coccidiomycosis, histoplasmosis, chromomycosis, paracoccidiodmycosis

*shouldnt be used for candida or dermatophyte infections

65
Q

Monitoring of ketoconazole for systemic infections

A

close monitoring warranted
-baseline and weekly monitoring of liver function

SEs: mult. serious drug interactions
-edema, orthostatic hypotension, fatigue, insomnia, pruritus, hot flashes, nausea, vomiting, myalgia, weakness, and more

66
Q

Voriconazole and posaconazole (systemic infections)

A

newer systemic tri-azole antifungals

  • oral or IV for aspergillosis
  • may be used for oral pharyngeal candidiasis resistant to other txs
67
Q

Flucytosine (5-FC) (systemic infections)

A

class: pyrimadines (diff. class diff. coverage), for severe systemic fungal infections

Infectious Disease (27 decks)

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