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antifungals Flashcards

1
Q

fungal infections
Mainly seen as?
* Cutaneous infections:
* Systemic infections:

A

Mainly seen as opportunistic or “superinfections”
* Cutaneous infections: common, chronic, seldom dangerous
* Systemic infections: difficult to diagnose, treat, and often lethal

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2
Q

Visible fungal infection of the mouth can tell you:

A
  1. Immune status
  2. Drugs they are taking
    ● Daily oral steroids?
    ● Immunosuppressive drugs: transplant?
    ● Antibiotics, Augmentin?
    ● Leukemia, lymphoma?
    ● Chemotherapy drugs – neutropenia?
    ● HIV/AIDS?
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3
Q

Treating Fungal Infections- Selective Toxicity

A
  • Rigid cell walls contain chitin and the cell membrane contains ergosterol
  • Selective toxicity achieved by targeting ergosterol
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4
Q

yeast and mold fungi spp

A

Molds (Dermatophytes)
Yeasts (Candida, Cryptococcus, Aspergillus)

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5
Q

Dermatophytes: Subgroup of ?
 Normal inhabitants of ?
 Produce ?
 Hyphal filaments?
 Invades ?

A

Dermatophytes: Subgroup of molds that live on skin.
 Normal inhabitants of skin, contagious, spread by contact.
 Produce keratinases that dissolve keratin
 Hyphal filaments penetrate into keratin
 Invades hair shafts & nail beds

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6
Q

Dermatophyte (Tinea) infections affect what tissues

A

Dermatophyte (Tinea) infections affect keratinized tissues
– skin, nails, hair, etc.

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7
Q

Three common pathogenic dermatophytes:

A

 Trichophyton Common
 Epidermophyton
 Microsporum

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8
Q

“Tinea” diseases: (“cutaneous mycoses”)

A

 Tinea capitis – scalp, common in children
 Tinea corporis – body
 Tinea pedis – athlete’s foot
 Tinea cruris – groin
 Tinea unguium – toenails (onychomycosis)

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9
Q

ALLYLAMINES

A

»Terbinafine (Lamisil oral or topical)
»Naftifine (Naftin)

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10
Q

»Terbinafine (Lamisil oral or topical) and Naftifine (Naftin) moa

A

Binds/inhibits squalene epoxidase
* Squalene precursors build up and are also toxic aiding toxicity
* Requires actively growing fungi

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11
Q

»Terbinafine (Lamisil oral or topical)
»Naftifine (Naftin)

A

ALLYLAMINES

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12
Q

allylamines only work on:

A
  • Fungicidal against Dermatophytes Only.
  • Weak fungistatic activity against Candida
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13
Q

allylamines adrs/ddi

A
  • Little drug interaction potential
  • Few side-effects
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14
Q

Candida albicans

A

Candida albicans
Candida: Most common fungal infection in mouth
» C. albicans normal habitat is the human oral cavity
» propensity to invade and cause disease when an imbalance is created

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15
Q

Oropharyngeal candidiasis (thrush)
 Symptoms:
 Many patients are
 Immunosuppressed patients with thrush often have?

A

Oropharyngeal candidiasis (thrush)
 Symptoms: cottony feeling in the mouth, loss of taste, and/or painful eating and
swallowing.
 Many patients are asymptomatic
 Immunosuppressed patients with thrush often have concomitant Candida esophagitis

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16
Q

Oropharyngeal thrush tx options

A
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17
Q

fluconazole tx of esphogeal thrush

A

Fluconazole - 400 mg as a loading dose and then 200 to 400 mg daily for 14 to 21days given orally

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18
Q

Clotrimazole (Mycelex) pros of use

A

highly efffective

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19
Q

Clotrimazole (Mycelex) cons of use

A
  • Ease of use (5x /day)
  • Expense
  • Drug interactions possible
  • Irritating to mucosa
  • Alters taste
  • Contains sugar
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20
Q

Miconazole (Oravig)

Pro:

A
  • Ease of use (daily troche)
  • Highly effective
  • Tasteless
  • No sugar
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21
Q

Miconazole cons

A
  • Expense
  • Drug Interactions
    possible
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22
Q

Nystatin pros

A
  • No drug interactions
  • Inexpensive
  • Not irritating to mucosa
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23
Q

nystatin cons

A
  • Ease of use (QID)
  • Ease of use (swish contact
    time)
  • Less effective
  • High sugar content
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24
Q

Angular cheilitis

A

 Acute or chronic inflammation of lateral
commissures
 Caused by excessive moisture and maceration
from saliva

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25
Q

Angular cheilitis

Angular cheilitis tx

A
  • Topical barriers keep moisture out, prevent
    reoccurrences
  • Barrier creams (eg, zinc oxide paste) or
    petrolatum
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26
Q

angular chelitis could be a sign of

A

May have Candida superinfection

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27
Q

azoles moa

A
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28
Q

First Generation Azoles

A

Miconazole, Clotrimazole: Not taken systemically
Clotrimazole & miconazole oral formulations less cariogenic; better tolerated vs Nystatin.

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29
Q

Miconazole (Oravig) dosage

A

50 mg (1 tablet) applied to upper gum once daily for 7-14 days
* Apply in morning after brushing. Alternate sides of mouth with each application; do not crush, chew, or swallow. Avoid chewing gum while in place.
* If the tablet does not adhere to gum or falls off within 6 hours of application, same tablet should be repositioned immediately.
* Exposure time important: goal entirety of waking hours.

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30
Q

Clotrimazole (Mycelex) dosage
* Metabolized in? contraindicated in?
* Avoid in combination with?
* Oral Troche?

A

10mg (1 troche) dissolved slowly 5 times daily for 7-14 days
* Metabolized in liver – 3A4. Contraindicated in liver disease.
* Avoid in combination with benzodiazapines; HIV
* Oral Troche for management of oral candidiasis

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31
Q

pt education with clotrimazole

A
  • Patient Education: 5 times daily. Swallow the saliva. No eating or drinking for 30min following medication
  • Dissolves over 30 minutes and remains in saliva for up to 3 hours
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32
Q

Second Generation Azole: Triazoles

A

Fluconazole (Diflucan), itraconazole, voriconazole, posaconazole, isavuconazole

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33
Q

First line drugs for systemic fungal infections

A

Second Generation Azole: Triazoles

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34
Q

triazoles ddi

A

Fewer drug-drug interactions and expanded spectrum
* Still metabolized via the cytochrome P450 enzyme system
* All azole agents are both metabolized by and slow down hepatic cytochrome P450 activity

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35
Q

triazole side effect profiles

A

Safer side-effect profiles than ketoconazole for systemic use

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36
Q

when would triazoles be used in dentistry

A

Esophogeal candidiasis or
refractory, resistant oral candidiasis.

37
Q

triazole resistance mechanisms

A

Resistance a big problem: 2 Mechanisms-
Efflux pumps & altered binding site on
demethylase

38
Q

Fluconazole (Diflucan)
* absorb
* t1/2
* excretion where
* ddi
* preg category
*

A

second gen azole

39
Q

Fluconazole (Diflucan) dentistry uses and rx

A

Esophogeal candidiasis or refractory, resistant oral candidiasis.
Rx: Fluconazole 200mg tablet, #15
400mg once, then 200mg PO daily x 14days

40
Q

VORICONAZOLE (VfendTM

41
Q

POSACONAZOLE (Noxafil™)

42
Q

Drugs that Stimulate Metabolism of Azoles

43
Q

Clotrimazole (Mycelex) troches example rx for topical

44
Q

Nystatin oral suspension example rx

45
Q

Oravig (Miconazole) example rx

46
Q

Polyenes Mechanism of Action

A
  • Binds ergosterol in fungal cell membrane
  • Forms pores in cell membrane
  • Cell contents leak out
  • Fungal cell death
47
Q

Polyenes: static or cidal?

A

Polyenes
»Binds to ergosterol in fungal membranes. Fungicidal

48
Q

Amphotericin B (Liposomal)

A

Broad spectrum fungicidal for intravenous use
* 1st line IV drug for most systemic yeasts: Histoplasmosis, Aspergillosis, Crypto.
* Standard Tx: Cryptococcal meningitis.
* Severe, potentially lethal side-effects (dose-dependent nephrotoxicity)

polyene

49
Q

Nystatin (Mycostatin): spectrum
* absorbed?
* Topical only for?
* Length of contact ?
* Suspension?
* Alternative to?

A

Nystatin (Mycostatin): Broad spectrum fungicidal
* No GI absorption - entirely excreted in feces – Pregnancy Category B (safe)
* Topical only for mucocutaneous candidiasis
* Length of contact important = 2 MINUTES
* Suspension, high sucrose concentration
* Alternative to clotrimazole/miconazole

50
Q

Patient Counseling with nystatin

A
  1. Swish in mouth then,
  2. Hold in mouth for as long as possible then,
  3. No eating or drinking for 30mins
51
Q

antifungals pneumonics

52
Q

Magic Mouthwash
* Common Indications:

A
  • Apthous stomatitis
  • Recurrent aphthous ulcers (RAU)
  • Chemo-induced oral mucositis
53
Q

Magic Mouthwash formula

A
  • NO STANDARD formula
  • 80% of healthcare facilities compound their own unique formula
54
Q

Magic Mouthwash Ingredients
* Most Common:

A
  • Diphenhydramine (Benadryl) >90%
  • Viscous lidocaine 90%
  • Magnesium hydroxide/ Aluminum hydroxide (Maalox) 80%
  • Nystatin 30%
  • Corticosteroids 10%
  • Tetracyclines 10%
55
Q

Diphenhydramine (Benadryl)

A
  • Antihistamine / reduce inflammatory process
  • Limit pain sensation
  • Reduce swelling, erythema
56
Q

why can bendryl be useful in magic mouthwash

A

useful for trauma, food allergens, or infections

57
Q

Viscous Lidocaine
* Relieves?
* IMPORTANT
* Use how much?
* action

A
  • Topical anesthetic
  • Relieves pain associated with irritated oral/pharyngeal mucous membranes
  • IMPORTANT: ingesting too much can lead to arrhythmias
  • Use minimal amounts
  • Swish and SPIT
58
Q

Magnesium Hydroxide / Aluminum Hydroxide
* role
* Primarily used as?

A
  • Antacid – Maalox and Mylanta
  • Primarily used as vehicle to enhance coating of other ingredients
    within the mouth
59
Q

Nystatin in magic mouthwash
* absorbed?
* Not appropriate for?
* Use if ?

A
  • Fungicidal polyene for mucocutaneous candidiasis
  • Nonabsorbable by oral route
  • Not appropriate for RAU or mucositis without fungal etiology
  • Use if active oral candidiasis infection in concert with RAU or mucositis
60
Q

polyenes

A

nystatin and amphotericin B

61
Q

Corticosteroids in magic mouth wash
* names
* Reduce
* Limit
* Reduce what symptoms
* Limited evidence for?

A
  • Hydrocortisone, dexamethasone, betamethasone, beclomethasone
  • Reduce inflammatory process
  • Limit pain sensation
  • Reduce swelling, erythema
  • Limited evidence for use / controversial
62
Q

Pain/Oral Irritation agents of magic mouth wash

A
  • Diphenhydramine - analgesic
  • Viscous Lidocaine - analgesic
  • Magnesium hydroxide/ aluminum hydroxide - vehicle
    • 1-to-1-to-1 ratio
  • Hx of arrhythmias, atrial fibrillation, etc – may avoid viscous lidocaine
  • Or 2-1-2 ratio
63
Q

Oral Mucocutaneous Candidiasis agents of magic mouthwash

A
  • Diphenhydramine - analgesic
  • Nystatin - antifungal
  • Magnesium hydroxide/ aluminum hydroxide - vehicle
  • Corticosteroid – in an opportunistic infection??? NO
64
Q

Administration of magic mouth wash

A
  • 2 tablespoons (30mL) every four to six hours
  • Swish and spit to avoid systemic side effects
  • Pharyngeal involvement?
65
Q

Side Effects of magic mouth wash

A
  • taste disturbances (49%)
  • burning and/or tingling in the oral cavity (29%)
  • drowsiness or any central nervous system adverse effects (11%)
  • gastrointestinal symptoms - constipation, diarrhea and nausea (11%)
66
Q

Evidence for magic mouth wash

A

The evidence is limited and controversial

67
Q

why is magic mouthwash controversial

A

Controversial because of Formulation Heterogeneity
* Diphenhydramine for all indications
* Maalox® for all indications
* Lidocaine for pain
* Nystatin for candidiasis
* Avoid steroids

68
Q

Binds/inhibits squalene epoxidase
* Squalene precursors build up and are also toxic aiding toxicity
* Requires actively growing fungi

A

»Terbinafine (Lamisil oral or topical) and Naftifine (Naftin) moa

69
Q
A

azoles moa

70
Q

Miconazole, Clotrimazole: Not taken systemically
Clotrimazole & miconazole oral formulations less cariogenic; better tolerated vs Nystatin.

A

First Generation Azoles

71
Q

50 mg (1 tablet) applied to upper gum once daily for 7-14 days
* Apply in morning after brushing. Alternate sides of mouth with each application; do not crush, chew, or swallow. Avoid chewing gum while in place.
* If the tablet does not adhere to gum or falls off within 6 hours of application, same tablet should be repositioned immediately.
* Exposure time important: goal entirety of waking hours.

A

Miconazole (Oravig) dosage

72
Q

10mg (1 troche) dissolved slowly 5 times daily for 7-14 days
* Metabolized in liver – 3A4. Contraindicated in liver disease.
* Avoid in combination with benzodiazapines; HIV
* Oral Troche for management of oral candidiasis

A

Clotrimazole (Mycelex) dosage

73
Q

Fluconazole (Diflucan), itraconazole, voriconazole, posaconazole, isavuconazole

A

Second Generation Azole: Triazoles

74
Q

second gen azole

A

Fluconazole (Diflucan)
* absorb
* t1/2
* excretion where
* ddi
* preg category
*

75
Q
A

VORICONAZOLE (VfendTM

76
Q
A

POSACONAZOLE (Noxafil™)

77
Q

Broad spectrum fungicidal for intravenous use
* 1st line IV drug for most systemic yeasts: Histoplasmosis, Aspergillosis, Crypto.
* Standard Tx: Cryptococcal meningitis.
* Severe, potentially lethal side-effects (dose-dependent nephrotoxicity)

polyene

A

Amphotericin B (Liposomal)

78
Q
  • Apthous stomatitis
  • Recurrent aphthous ulcers (RAU)
  • Chemo-induced oral mucositis
A

Magic Mouthwash
* Common Indications:

79
Q
  • Antihistamine / reduce inflammatory process
  • Limit pain sensation
  • Reduce swelling, erythema
A

Diphenhydramine (Benadryl)

80
Q
  • Topical anesthetic
  • Relieves pain associated with irritated oral/pharyngeal mucous membranes
  • IMPORTANT: ingesting too much can lead to arrhythmias
  • Use minimal amounts
  • Swish and SPIT
A

Viscous Lidocaine
* Relieves?
* IMPORTANT
* Use how much?
* action

81
Q
  • Antacid – Maalox and Mylanta
  • Primarily used as vehicle to enhance coating of other ingredients
    within the mouth
A

Magnesium Hydroxide / Aluminum Hydroxide
* role
* Primarily used as?

82
Q
  • Fungicidal polyene for mucocutaneous candidiasis
  • Nonabsorbable by oral route
  • Not appropriate for RAU or mucositis without fungal etiology
  • Use if active oral candidiasis infection in concert with RAU or mucositis
A

Nystatin in magic mouthwash
* absorbed?
* Not appropriate for?
* Use if ?

83
Q

nystatin and amphotericin B

84
Q
  • Hydrocortisone, dexamethasone, betamethasone, beclomethasone
  • Reduce inflammatory process
  • Limit pain sensation
  • Reduce swelling, erythema
  • Limited evidence for use / controversial
A

Corticosteroids in magic mouth wash
* names
* Reduce
* Limit
* Reduce what symptoms
* Limited evidence for?

85
Q
  • Diphenhydramine - analgesic
  • Viscous Lidocaine - analgesic
  • Magnesium hydroxide/ aluminum hydroxide - vehicle
    • 1-to-1-to-1 ratio
  • Hx of arrhythmias, atrial fibrillation, etc – may avoid viscous lidocaine
  • Or 2-1-2 ratio
A

Pain/Oral Irritation agents of magic mouth wash

86
Q
  • Diphenhydramine - analgesic
  • Nystatin - antifungal
  • Magnesium hydroxide/ aluminum hydroxide - vehicle
  • Corticosteroid – in an opportunistic infection??? NO
A

Oral Mucocutaneous Candidiasis agents of magic mouthwash

87
Q

angular chelitis rx

A

clotrimazole ointment BID 1-3wks

88
Q

which antifungal has the lowest chance of ddi

89
Q

which antifungal has the highest chance of ddi

A

fluconazole

pharm 2 (20 decks)

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