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Antifungals Flashcards

1
Q

Which Antifungals alter cell membrane permeability?

3

A

Azoles
Polyenes
Terbinafine

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2
Q

Which antifungals block nucleic scid synthesis?

A

Flucytosine

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3
Q

Which antifungals disrupt microtuble function?

A

Griseofulvin

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4
Q 
Name the drugs that make up the azole class of antifungals?
7
A 
Miconazole
Clotrimazole
Ketoconazole
Fluconazole
Itraconazole
Voriconazole
Posaconazole
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5
Q 
Name the drugs that make up the polyene class of antifungals?
2
A

Nystatin

Amphoteracin B

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6
Q

What are the topical Drugs for Cutaneous Fungal Infections

4

A

Azoles:
Miconazole;
Clotrimazole;
Ketoconazole

Polyene: Nystatin

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7
Q

What are the Systemic Drugs for Superficial Fungal Infections?
3

A

Griseofulvin
Terbinafine
Itraconazole

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8
Q

What are the Systemic Drugs for Systemic Fungal Infections?

7

A

Amphoteracin B

Azoles:  
Ketoconazole; 
Fluconazole; 
Itraconazole;
Vorconazole; 
Posaconazole

Flucytosine (5-FC)

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9
Q

Are topical antifungals fungicidal or fungostatic?

A

Fungicidal

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10
Q

MOA of topical azole antifungals?

A

Impairs the formation of fungal cell membranes therefore increasing permeability
-Intracellular contents leak out leading to cell death

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11
Q

What kind of infections are topical azole antifungals used for?
4

A

Tinea corporis,
tinea cruris,
tinea pedis,
cutaneous candidiasis

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12
Q

Contraindications for topical azole antifungals?

3

A
  1. Pregnancy, lactation
  2. Use with caution in liver failure
  3. Ketoconazole not for use with history of sulfa allergy
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13
Q

Dosage forms of topical azole antifungals?

A

Lotion or powder
Apply twice daily for 2-4 weeks
Continue therapy for 1 week after lesions clear

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14
Q

What do topical azole antifungals inhibit?

A

CYP450
Mechanism of action
–Inhibit synthesis of ergosterol (cell membrane)

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15
Q

SE of topical azole antifungals?

4

A

Pruritis, irritation, burning or stinging

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16
Q

Topical Azole Antifungals: Clotrimazole indications?

3

A
  1. Cutaneous candidiasis (topical)
  2. Vulvovaginal candidiasis (topical)
  3. Oropharyngeal candidiasis (thrush) oral formulation
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17
Q

Topical Azole Antifungals: Clotrimazole contraindaicaitons?

A

Hypersensitivity to clotrimazole or any component of the formulation

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18
Q

Dosage for Topical Azoles: Clotrimazole?

3

A

Lotion
Intravaginal sepository
Troche

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19
Q

Clotrimazole: MOA

Absoprtion? 2

A

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

Very little systemic absorption from topical formula
Troche- 3hours inhibitory concetraion

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20
Q

Clotrimazole adverse effects
Topical?
Oral?3

HOw would we monitor Clotrimazole?

A

vulvovaginal burning

Abnormal liver function tests
Pruritus
Nausea, vomiting

Periodic liver function tests

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21
Q

Topical Azoles: Ketoconazole

formulations?4

A

Cream, foam, gel or shampoo

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22
Q

Indications for Ketoconazole?
6

What can’t we use it with?

A 
Tinea corporis, 
tinea cruris, 
tinea pedis, 
cutaneous candidiasis 
(Same as clotrimazole)

+ Seborrheic dermatitis and Tinea Versicolor

Sulfas

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23
Q

Topical Azoles: Miconazole formulations?

4

A

Aerosol,
Powder Aerosol,
intravaginal suppository,
cream, ointment, lotion

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24
Q

Indications for Miconazole?

6

A

Tinea corporis,
tinea cruris,
tinea pedis,
cutaneous candidiasis

+ Tinea Versicolor + Vulvovaginal candidiasis

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25
What dosage forms of miconazole would interfere with warfarin?
Intravaginal suppositories may interfere
26
Topical Polyene: Nystatin (Mycostatin) indications? Contraindications?
Cutaneous and mucocutaneous infections caused by Candidia Oral and intestinal Candidia infections Hypersensitivity reaction
27
Mycostatin mechanism of action?
Binds to sterols in fungal cell membrane and changes the cell wall permeability leading to leakage of intracellular contents
28
Mycostatin pharmacokinetics/dynamics Onset of action? Systemic absorption? Drug interactions?
``` Onset of action: Relief of symptoms within 24-72 hours Systemic absorption None Drug interactions None ```
29
Mycostatin adverse effects | 3
Contact dermatitis Stevens-Johnson syndrome Oral Nausea, vomiting, diarrhea
30
Griseofulvin indications? | 2
1. Used to treat tinea infections of the skin, hair and nails 2. Most commonly used for the treatment of tinea capitis
31
Mechanism of action for Griseofulvin? | 2
1. Inhibits fungal cell division | 2. Binds to human keratin making it resistant to fungal invasion
32
Duration of therapy for Griseofulvin? Tinea capitis: Tinea unguium:
Tinea capitis 4-6 weeks Tinea unguium 4-6 months or longer
33
Things to remember about administration? | 2
Administration - -Fatty meal (peanut butter or icecream) can increase GI absorption - -With food or milk to decrease GI upset
34
Contraindications and precautions with the administration of Griseofulvin?3 Pregnancy category? Lactation?
Liver failure Porphyria Use with caution if history of penicillin allergy as potential for cross reactivity Pregnancy (category X) Breast feeding not recommended
35
Periodic monitoring required if long term use necessary for Griseofulvin. What should we monitor? 3
Renal function Liver function CBC to watch for granulocytopenia
36
Describe Griseofulvin drug interactions? What specific ones? 5
Many drug interactions due to it’s effects on CYP1A2, CYP2C9 and CYP3A4. Warfarin, oral contraceptives, alcohol (disulfiram-like reaction), barbiturates, cyclosporine and others
37
Griseofulvin adverse reactions?
``` Photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme Jaundice, elevated liver function tests Granulocytopenia Dizziness, fatigue, headache Diarrhea, nausea, vomiting Drug induced lupus like syndrome ```
38
Describe how the dosing changes with Griseofulvin and the particle size of the two formulas?
The smaller the particle size the greater the bioavailablity requiring dose adjustments between the two formulations Microsize and Ultramicrosize
39
Terbinafine(Lamisil) indications? 2 Contraindications?
Oncychomycosis of the toenails, fingernails Tinea capitis Hypersensitivity
40
Terbinafine mechanism of action
Creates ergosterol deficiency within the cell wall leading to cell death
41
``` Terbinafine pharmacodynamics/kinetics: Half life? Distribution? Protein bound? Metabolism? ```
Effective half life 36 h Distribution to the sebum and skin 99% plasma bound (drug interactions) Hepatic metabolism
42
What are two very important Terbinafine drug interactions | we should remember?
Due to inhibition of CYP450 enzymes there are some significant drug interactions including metoprolol and tramadol (for oral formulation)
43
Terbinafine side effects 3 big ones 5 others that happen occassionally
Headache Diarrhea Liver function tests ``` Burning Contact dermatitis Dryness Pruritus Rash ```
44
Itraconazole (Sporanox) indications for topical fungus?
Onychomycosis | lamisil first line though
45
Itraconazole (Sporanox) contraindications | 5
1. Hypersensitivity to intraconazole or other azoles 2. Concurrent administration with other drugs that act at the CYP450 system 3. Ventricular dysfunction (negative inotrope) 4. CHF 5. Pregnancy or intend to become pregnant
46
Itraconazole (Sporanox) Pharmacodynamics/kinetics What does it require for optimal absorption? Protein bound? Half life? Metabolism?
1. Requires gastric acidity for optimal absorption Better absorbed with food (capsule) 2. 99.8% protein bound 3. Half life is about 21 hours 4. Metabolized by the liver
47
Itraconazole (Sporanox) Drug interactions?
A LOT | Need to do a drug interaction checker before you prescribe
48
Itraconazole (Sporanox) Adverse effects
``` Nausea, diarrhea Edema Headache Rash Abnormal LFTs Heart failure Arrhythmia Hearing loss Many others…. ```
49
Itraconazole (Sporanox) Monitoring. 3
1. Baseline liver function tests 2. Monthly LFTs (if long term therapy) 3. Serum concentrations to assure therapeutic levels
50
Amphoteracin B is used when? Dosage form? Indications? Side effects? 4
Systemic antifungal for use in severe fungal infections. IV only severe systemic fungal and fungal CNS infections that are progressive and potentially life threatening Anaphylaxis, infusion reaction, leukoencephalopathy (damage to brain white matter), nephrotoxicity
51
Amphotericin B Mechanism of Action? Monitoring? 4 Some drug interactions? 4
Binds to ergosterol and alters cell membrane permeability and may also stimulate the macophages. renal and liver function, electrolytes, PT/PTT, CBC aminoglycosides, other antifungal agents, corticosteroids, cyclosporine
52
Itraconazole (Sporanox) systemic indications? | 5
1. Aspergillosis 2. Blastomycosis 3. Esophageal and oropharyngeal candidiasis (oral soln) 4. Coccidioidomycosis 5. Histoplasmosis
53
Itraconazole (Sporanox) systemic contraindications?
1. Hypersensitivity to intraconazole or other azoles 2. Concurrent administration with other drugs that act at the CYP450 system 3. Ventricular dysfunction (negative inotrope) 4. CHF 5. Pregnancy or intend to become pregnant
54
Fluconazole (Diflucan) indications | 4
``` Blastomycosis -CNS disease Candidiasis -Candidemia, endocarditis, oropharyngeal, prophylaxis, vaginal, and more… Coccidioidomycosis -Meningitis, pneumonia, prophylaxis Crypococcosis -Meningitis, pneumonia ``` Blastomycosis Candidiasis Coccidioidomycosis Crypococcosis
55
Can use as a one time dose for a vaginal yeast infection. it is a oral medication?
Fluconazole (Diflucan)
56
Fluconazole (Duflucan) contraindications? | 2
1. Hypersensitivity to fluconazole or other azoles | 2. Coadministration of CYP3A4 substrates which may lead to QT prolongation (cisapride, primozide or quinidine)
57
Fluconazole (Diflucan) dosage forms?
IV and oral formulations
58
Fluconazole (Diflucan) pharmacokinetics/dynamics Distribution? Protein bound? Half life?
Widely throughout the body Good penetration into CSF, eye, peritoneal fluid, sputum, skin and urine Protein binding 11-12% in the plasma Not highly protein bound But increases reavitity of other drugs Half life - 30 hours
59
Fluconazole (Diflucan) Adverse effects? | 5
1. Pregnancy category C/D 2. Headache, dizziness 3. Nausea, vomiting, diarrhea 4. Elevated liver function tests 5. QT prolongation
60
Fluconazole (Diflucan) Monitoring? | 3
1. Baseline liver function tests | 2. Periodic liver function, renal function and potassium
61
Systemic Ketoconazole Warnings Indications?
Only give it if they will die without it Use restricted only for the treatment of SYSTEMIC life threatening fungal infections when other safer agents cannot be used --Blastomycosis, coccidiomycosis, histoplasmosis, chromomycosis, paracoccidioiodmycosis Should NOT be used for candida or dermatophyte infections
62
Ketoconazole: Close monitoring is warranted. Of what?
Baseline and weekly monitoring of liver function

Infectious Disease (29 decks)

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