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Infectious Disease > Antifungals > Flashcards

Antifungals Flashcards

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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
Systemic drugs for superficial fungal infections
Griseofulvin, terbinafine, itraconazole | -for hair, skin and nails
26
Griseofulvin indications
used to tx tine infections of skin, hair and nails | -most commonly used for tx of tine capitis (scalp)
27
Griseofulvin MOA
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
Duration fo Griseofulvin therapy
``` 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
CIs and precautions with administration of Griseofulvin
- liver failure - porphyria (porphyrin accum) - preg (X) - caution if hx of pcn allergy - breast feeding not recom.
30
What periodic monitoring is required if pt is on long term tx of griseofulvin
renal fxn, liver fxn, and CBC to watch for granulocytopenia | * get CBC and CMP
31
Drug interactions of Griseofulvin
many due to its effects on CYP1A2, CYP2C9, CYP3A4 | -warfarin, oral contraceptives, alcohol, barbiturates, cyclosporine and others
32
Adverse reactions of griseofulvin
photosensitivity, SJS, toxic epidermal necrolysis, erythema multiforme, jaundice, elevated LFTs, granulocytopenia, dizziness, fatigue, HA, N/V/D, drug induced lupus like syndrome
33
Dose adjustments of griseofulvin dependent on?
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
Terbinafine (Lamisil)
oral/systemic formula: - oncychomycosis of toenails and fingernails - tinea capitis CIs: Hypersensitivity
35
Terbinafine MOA
creates ergosterol deficiency within the cell wall leading to cell death
36
Dosing of Terbinafine
oral: onychomcosis of the fingernails -> 250 mg/day x 6 weeks oncychomycosis of the toenails: 250 mg day x 12 weeks
37
Terbinafine pharmacodynamics/kinetics
effective half life 36 h - distribution to the sebum and skin - 99% plasma bound (drug interactions) - hepatic metabolism
38
drug interactions of Terbinafine
due to inhibition of CYP450 enzymes there are some sig. drug interactions including metoprolol (B blocker), and tramadol - pain med (oral formulation)
39
Terbinafine SEs
HA, diarrhea, LFTs, burning, contact dermatitis, dryness, pruritus, rash
40
Itraconazole (sporanox) indications for superficial infections
**Onychomycosis
41
Itraconazole (sporanox) CIs
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
Itraconazole (Sporanox) Pharmacodynamics/Kinetics
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
Itraconazole (Sporanox) drug interactions
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
Itraconazole (sporanox) adverse effects
Nausea, diarrhea, edema (from L. ventricular dysfunction), HA, rash, Abnorm. LFTs, heart failure, arrhythmia, hearing loss, and many more
45
Itraconazole (sporanox) monitoring
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
Systemic drugs for systemic fungal infections (the worst of the worst)
``` Amphoteracin B (stay away from), azoles: ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, flucytosine (5-FC) ```
47
Amphoteracin B (Amphoterrible!!)
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
Amphotericin B MOA
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
Drug interactions with Amphotericin B
aminoglycosides, antifungal agents, corticosteroids, cyclosporine
50
Itraconazole (Sporanox) indications - for systemic infections
(for superficial -> onychomycosis) systemic: aspergillosis, blastomycosis, esophageal and oropharyngeal candidiasis (oral soln), coccidioidomycosis, histoplasmosis
51
Itraconazole (sporanox) CIs
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
Itraconazole (sporanox) pharmodynamics/kinetics
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
Itraconazole (Sporanox) drug interactions
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
Itraconazole (sporanox) adverse effects (for systemic use)
Nausea, diarrhea, edema, HA, rash, Abnorm. LFTs, Heart failure, arrhythmia, hearing loss, and many others
55
Itraconazole (sporanox) monitoring
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
Fluconazole (diflucan) indications
- Blastomycosis (CNS disease) - candidiasis: candidemia, endocarditis, orpharyngeal, prophylaxis, vaginal and more - coccidioidomycosis: meningitis, pneumonia, prophylaxis - crypococcosis: meningitis, pneumonia
57
Fluconazole (Duflucan) CIs
hypersensitivity to fluconazole or other azaleas | -coadmin. of CYP3A4 substrates which may lead to QT prolongation (cisapride, primozide, or quinidine)
58
FLuconazole (Diflucan) route and dose
IV and oral | dose dep. in disease process
59
Fluconazole (diflucan) pharmacokinetics/dynamics
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
Fluconazole (Diflucan) Drug interactions
``` 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
Fluconazole (Diflucan) Adverse effects
``` pregnancy: C/D HA, dizziness N/V/D elev LFTs QT prolongation ```
62
Fluconazole (Diflucan) monitoring
Baseline LFTs | periodic LF, RF and K
63
Systemic ketoconazole (Nizoral) FDA warning
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
Ketoconazole indications (oral) for systemic infections
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
Monitoring of ketoconazole for systemic infections
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
Voriconazole and posaconazole (systemic infections)
newer systemic tri-azole antifungals - oral or IV for aspergillosis - may be used for oral pharyngeal candidiasis resistant to other txs
67
Flucytosine (5-FC) (systemic infections)
class: pyrimadines (diff. class diff. coverage), for severe systemic fungal infections

Infectious Disease (27 decks)

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