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Infectious Disease > Antifungals > Flashcards

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
Q

What dosage forms of miconazole would interfere with warfarin?

A

Intravaginal suppositories may interfere

26
Q

Topical Polyene: Nystatin (Mycostatin) indications?

Contraindications?

A

Cutaneous and mucocutaneous infections caused by Candidia

Oral and intestinal Candidia infections

Hypersensitivity reaction

27
Q

Mycostatin mechanism of action?

A

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

28
Q

Mycostatin pharmacokinetics/dynamics
Onset of action?
Systemic absorption?
Drug interactions?

A 
Onset of action:
Relief of symptoms within 24-72 hours
Systemic absorption
None
Drug interactions
None
29
Q

Mycostatin adverse effects

3

A

Contact dermatitis
Stevens-Johnson syndrome

Oral
Nausea, vomiting, diarrhea

30
Q

Griseofulvin indications?

2

A
  1. Used to treat tinea infections of the skin, hair and nails
  2. Most commonly used for the treatment of tinea capitis
31
Q

Mechanism of action for Griseofulvin?

2

A
  1. Inhibits fungal cell division

2. Binds to human keratin making it resistant to fungal invasion

32
Q

Duration of therapy for Griseofulvin?
Tinea capitis:
Tinea unguium:

A

Tinea capitis 4-6 weeks

Tinea unguium 4-6 months or longer

33
Q

Things to remember about administration?

2

A

Administration

  • -Fatty meal (peanut butter or icecream) can increase GI absorption
  • -With food or milk to decrease GI upset
34
Q

Contraindications and precautions with the administration of Griseofulvin?3

Pregnancy category?
Lactation?

A

Liver failure
Porphyria
Use with caution if history of penicillin allergy as potential for cross reactivity

Pregnancy (category X)
Breast feeding not recommended

35
Q

Periodic monitoring required if long term use necessary for
Griseofulvin. What should we monitor?
3

A

Renal function

Liver function

CBC to watch for granulocytopenia

36
Q

Describe Griseofulvin drug interactions?

What specific ones?
5

A

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
Q

Griseofulvin adverse reactions?

A 
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
Q

Describe how the dosing changes with Griseofulvin and the particle size of the two formulas?

A

The smaller the particle size the greater the bioavailablity requiring dose adjustments between the two formulations

Microsize and Ultramicrosize

39
Q

Terbinafine(Lamisil) indications?
2

Contraindications?

A

Oncychomycosis of the toenails, fingernails
Tinea capitis

Hypersensitivity

40
Q

Terbinafine mechanism of action

A

Creates ergosterol deficiency within the cell wall leading to cell death

41
Q 
Terbinafine pharmacodynamics/kinetics:
Half life?
Distribution?
Protein bound?
Metabolism?
A

Effective half life 36 h
Distribution to the sebum and skin
99% plasma bound (drug interactions)
Hepatic metabolism

42
Q

What are two very important Terbinafine drug interactions

we should remember?

A

Due to inhibition of CYP450 enzymes there are some significant drug interactions including metoprolol and tramadol (for oral formulation)

43
Q

Terbinafine side effects
3 big ones
5 others that happen occassionally

A

Headache
Diarrhea
Liver function tests

Burning
Contact dermatitis
Dryness
Pruritus
Rash
44
Q

Itraconazole (Sporanox) indications for topical fungus?

A

Onychomycosis

lamisil first line though

45
Q

Itraconazole (Sporanox) contraindications

5

A
  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
Q

Itraconazole (Sporanox) Pharmacodynamics/kinetics
What does it require for optimal absorption?

Protein bound?
Half life?
Metabolism?

A
  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
Q

Itraconazole (Sporanox) Drug interactions?

A

A LOT

Need to do a drug interaction checker before you prescribe

48
Q

Itraconazole (Sporanox) Adverse effects

A 
Nausea, diarrhea
Edema
Headache
Rash
Abnormal LFTs
Heart failure
Arrhythmia
Hearing loss
Many others….
49
Q

Itraconazole (Sporanox) Monitoring. 3

A
  1. Baseline liver function tests
  2. Monthly LFTs (if long term therapy)
  3. Serum concentrations to assure therapeutic levels
50
Q

Amphoteracin B is used when?

Dosage form?

Indications?

Side effects?
4

A

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
Q

Amphotericin B Mechanism of Action?

Monitoring?
4

Some drug interactions?
4

A

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
Q

Itraconazole (Sporanox) systemic indications?

5

A
  1. Aspergillosis
  2. Blastomycosis
  3. Esophageal and oropharyngeal candidiasis (oral soln)
  4. Coccidioidomycosis
  5. Histoplasmosis
53
Q

Itraconazole (Sporanox) systemic contraindications?

A
  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
Q

Fluconazole (Diflucan) indications

4

A 
Blastomycosis
-CNS disease
Candidiasis
-Candidemia, endocarditis, oropharyngeal, prophylaxis, vaginal, and more…
Coccidioidomycosis
-Meningitis, pneumonia, prophylaxis
Crypococcosis
-Meningitis, pneumonia

Blastomycosis
Candidiasis
Coccidioidomycosis
Crypococcosis

55
Q

Can use as a one time dose for a vaginal yeast infection. it is a oral medication?

A

Fluconazole (Diflucan)

56
Q

Fluconazole (Duflucan) contraindications?

2

A
  1. Hypersensitivity to fluconazole or other azoles

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

57
Q

Fluconazole (Diflucan) dosage forms?

A

IV and oral formulations

58
Q

Fluconazole (Diflucan) pharmacokinetics/dynamics
Distribution?
Protein bound?
Half life?

A

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
Q

Fluconazole (Diflucan) Adverse effects?

5

A
  1. Pregnancy category C/D
  2. Headache, dizziness
  3. Nausea, vomiting, diarrhea
  4. Elevated liver function tests
  5. QT prolongation
60
Q

Fluconazole (Diflucan) Monitoring?

3

A
  1. Baseline liver function tests

2. Periodic liver function, renal function and potassium

61
Q

Systemic Ketoconazole Warnings

Indications?

A

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
Q

Ketoconazole: Close monitoring is warranted. Of what?

A

Baseline and weekly monitoring of liver function

Infectious Disease (29 decks)

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