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ID Pharm > Antifungals > Flashcards

Antifungals Flashcards

1
Q

What are the classes of azoles?

A

Imidazoles and Triazoles

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2
Q

Azole MOA?

A

impairs the synthesis of ergosterol resulting in:
increased cellular permeability
leakage of cellular contents
inhibition of fungal growth

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3
Q

Azole Side Effects

A

GI: nausea, vomitting, diarrhea
Hepatotoxicity - CYP450 metabolism
Rash

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4
Q

Imidazole drugs

A

Ketoconazole
Clotrimazole
Miconazole
KCM

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5
Q

KCM formulations and role

A

creams, lotions, shampoos, vaginal tablets, lozenges, and solutions
Tx: vaginal and epidermal candidiasis

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6
Q

Ketoconazole Formulations

A

Only imidazole to come in oral form in addition to other forms

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7
Q

Ketoconazole Treats what?

A 
Tx:
Candida sp
Malassezia furfur
Blastomyces dermatitidis
Coccidioides sp
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8
Q

Ketoconazole DI and BBW

A

Many drug-drug interactions from CYP metabolism

BBW: hepatotoxicity -> use triazoles first

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9
Q

Triazoles

A 
Fluconazole
Itraconazole
Terconazole
Voriconazole
Posaconazole
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10
Q

Fluconazole Facts

A

broad spectrum of activity
oral dosage
Does not undergo 1st pass metab. –> >90% bioavail.
Half-life ~ 30 hrs

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11
Q

Fluconazole Spectrum of Activity

A 
Cadida sp., Cryptococcus neoformans
Some dimorphic fungi - coccidioidomycosis
M. furfur
Prototheca sp.
Some molds and dermatophytes
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12
Q

Fluconazole DOC for what?

A

For susceptible fungal infections:
Invasive and noninvasive candidiasis and cryptococcal inf
When topical azoles not enough
Can give prophylactically in immunocompromised
Not all candida species susceptible

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13
Q

Fluconazole CYP interactions

A

Inhibits 2C9, 2C19, 3A4

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14
Q

Itraconazole

A

Oral or IV
Similar to ketocon. – also covers aspergillus sp, sprothix schenckii, and histoplasmosis
Potent CYP INHIBITOR
DOC for dimorphic fungal infx like histoplasmosis

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15
Q

Itraconazole SE

A

20% have transient visual disturbances - photophobia, blurred vision, color changes
15% have dose related hallucinations

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16
Q

Itraconazole BBW

A

avoid in patients with systolic heart failure due to inotropic effects
especially oral doses over 400 mg

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17
Q

Voriconazole

A

Oral or IV
Extended/Broad spectrum of activity: resistant aspergillus or candida
Superior to amphotericin B for aspergillus

18
Q

Voriconazole Metabolism

A

CYP450 metabolism w/ many drug-drug interaction

Adjust dose for renal failure

19
Q

Posconazole

A

Expanded spectrum of activity - resistant Candida
Active against zygomycetes**
Oral suspension only

20
Q

Posconazole PK/PD

A

Poor bioavailability - high-fat meal increases bioavail 400%

SE: GI disturbances, elevation of LFTs

21
Q

Posconazole Indication

A

prophylaxis of fungal infections in neutropenic patients

Treatment of oropharyngeal candidiasis

22
Q

Polyenes

A

Amphotericin B and Nystatin
MOA: bind to ergosterol and disrupt fungal cell membrane
Causes increased cell permeability and leakage of intracellular contents

23
Q

Amphotericin B

A

Polyene
IV for systemic infections
DOC for cryptococcal meningitis

24
Q

Amphotericin B Spectrum of Activity

A

The majority of invasive fungi

Candida sp, Aspergillus sp, dimorphic fungi, cryptococcus

25
Q

Amphotericin B Toxicities

A 
Nephrotoxicity
Hematologic toxicitiy
Infusion related reactions
Thrombophlebitits
Monitor for toxicities - use clinical pharmacist
26
Q

Amphotericin B premedication regimens

A

Acetaminophen: prevent fever, headache
Heparin: prevent thrombophlebitis
NS: decreases nephrotoxicity
Correct electrolyte disturbances

27
Q

Nystatin

A 
Polyenes
Oral and topical forms
No significant drug interactions
Poorly absorbed from gut
Well tolerated - high dose causes GI issues
28
Q

Nystatin Indications

A

cutaneous and mucocutaneous infections from candida
Oral and intestinal Candida infections
1-10% have GI diarrhea, nausea, stomach pain, vomiting

29
Q

Nystatin Formulations

A

Cream 100,000 U/g - 2-3/day
Ointment 100,000 U/g - 2-3/day
Powder 100,000 U/g - 2-3/day
Oral suspension for thrush - 400,000-600,000 U/day QID
Tablets - Intestinal Infx 500,000-1mil U po q8H

30
Q

Allylamines

A

Terbinafine (Lamsil)

oral and topical

31
Q

Terbinafine MOA, SOA, Indications

A

MOA: inhibits squalene monooxygenase used in ergosterol synthesis
SOA: dermatophytes - does not treat candida or mold
Indications: 1st line for onychomycosis 4-12 wk therapy

32
Q

Terbinafine Monitoring, PK/PD

A 
Monitoring: check LFTs, CBC (decreased ALC)
36 hr half-life
Distribution to sebum and skin
99% plasma protein bound
Hepatic metabolism
33
Q

Echinocandins

A 
Glucan synthesis inhibitors
Caspofungin 
Micafungin
Anidulafungin
Only available IV
34
Q

Echinocandin Indications

A

Invasisve aspergillosis
Esophageal candidiasis
Intraabdominal abscesses
Peritonitis
Pleural space infx from candida sp
Cryptococcus does not have glucan = resistant
Can treat aspergillosis but not -cidal or -static

35
Q

Echinocandin MOA

A

inhibits synthesis of 1,3-beta-d-glucan synthase (component of fungal cell walls)
Results in intracellular leakage and cell death

36
Q

Echinocandin

A

Good safety profile - no CYP interactions

Good for treatment of invasive candidiasis and esophageal candidiasis

37
Q

Antimetabolite All

A

5-flurocytosine - flucocytosine
MOA: inhibits DNA and RNA synthesis of fungal cells
For: cryptococcus and candida
With Amphotericin B to treat cryptococcal meningitis
SE: GI and BM depression

38
Q

Griseofulvin Indications and Administration

A

Grifulvin V, Gris-PEG
For tinea capitis and tinea of skin, hair and nails
Tablet or suspension
Take with fatty meal to increase absorption
Food or milk decrease GI upset

39
Q

Griseofulvin MOA

A

Inhibits fungal cell division

Binds to human keratin making it resistant to fungal invasion

40
Q

Griseofulvin CI and Precautions and monitoring

A

Liver failure - LFT elevation
Porphyria
Pregnancy Category X
Breast feeding not recommended
Use with caution if PCN allergy due to cross reactivity
Monitor: renal and liver fxn, and CBC for granulocytopenia

41
Q

Griseofulvin DI and Adverse Reactions

A 
CYP 1A2, 2C9, 3A4 metabolism
warfarin, OCP, alcohol, barbituate, cyclosporine interactions
AR:
photosensitivity, stevens-johnson, toxic epidermal necrolysis, erythema multiforme
Jaundice
Granulocytopenia
dizziness, fatigue, HA
diarrhea, nausea, vomiting
drug induced lupus like syndrome
42
Q

Griseofulvin Bioavailability

A

The smaller the particle size, the greater the bioavailability
Microsize: suspension - grifulvin V tablets - cheaper
Ultramicrosize: Gris-PEG tablets - smaller = greater bioavailability and smaller dose needed

ID Pharm (6 decks)

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