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antifungals Flashcards

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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
# Angular cheilitis Angular cheilitis tx
* Topical barriers keep moisture out, prevent reoccurrences * Barrier creams (eg, zinc oxide paste) or petrolatum
26
angular chelitis could be a sign of
May have Candida superinfection
27
azoles moa
28
First Generation Azoles
Miconazole, Clotrimazole: Not taken systemically Clotrimazole & miconazole oral formulations less cariogenic; better tolerated vs Nystatin.
29
Miconazole (Oravig) dosage
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.
30
Clotrimazole (Mycelex) dosage * Metabolized in? contraindicated in? * Avoid in combination with? * Oral Troche?
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
31
pt education with clotrimazole
* 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
32
Second Generation Azole: Triazoles
Fluconazole (Diflucan), itraconazole, voriconazole, posaconazole, isavuconazole
33
First line drugs for systemic fungal infections
Second Generation Azole: Triazoles
34
triazoles ddi
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
35
triazole side effect profiles
Safer side-effect profiles than ketoconazole for systemic use
36
when would triazoles be used in dentistry
Esophogeal candidiasis or refractory, resistant oral candidiasis.
37
# triazole resistance mechanisms
Resistance a big problem: 2 Mechanisms- Efflux pumps & altered binding site on demethylase
38
Fluconazole (Diflucan) * absorb * t1/2 * excretion where * ddi * preg category *
second gen azole
39
Fluconazole (Diflucan) dentistry uses and rx
Esophogeal candidiasis or refractory, resistant oral candidiasis. Rx: Fluconazole 200mg tablet, #15 400mg once, then 200mg PO daily x 14days
40
VORICONAZOLE (VfendTM
41
POSACONAZOLE (Noxafil™)
42
Drugs that Stimulate Metabolism of Azoles
43
Clotrimazole (Mycelex) troches example rx for topical
44
Nystatin oral suspension example rx
45
Oravig (Miconazole) example rx
46
Polyenes Mechanism of Action
* Binds ergosterol in fungal cell membrane * Forms pores in cell membrane * Cell contents leak out * Fungal cell death
47
Polyenes: static or cidal?
Polyenes »Binds to ergosterol in fungal membranes. Fungicidal
48
Amphotericin B (Liposomal)
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
Nystatin (Mycostatin): spectrum * absorbed? * Topical only for? * Length of contact ? * Suspension? * Alternative to?
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
Patient Counseling with nystatin
1. Swish in mouth then, 2. Hold in mouth for as long as possible then, 3. No eating or drinking for 30mins
51
antifungals pneumonics
52
Magic Mouthwash * Common Indications:
* Apthous stomatitis * Recurrent aphthous ulcers (RAU) * Chemo-induced oral mucositis
53
Magic Mouthwash formula
* NO STANDARD formula * 80% of healthcare facilities compound their own unique formula
54
Magic Mouthwash Ingredients * Most Common:
* Diphenhydramine (Benadryl) >90% * Viscous lidocaine 90% * Magnesium hydroxide/ Aluminum hydroxide (Maalox) 80% * Nystatin 30% * Corticosteroids 10% * Tetracyclines 10%
55
Diphenhydramine (Benadryl)
* Antihistamine / reduce inflammatory process * Limit pain sensation * Reduce swelling, erythema
56
why can bendryl be useful in magic mouthwash
useful for trauma, food allergens, or infections
57
Viscous Lidocaine * Relieves? * IMPORTANT * Use how much? * action
* 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
Magnesium Hydroxide / Aluminum Hydroxide * role * Primarily used as?
* Antacid – Maalox and Mylanta * Primarily used as vehicle to enhance coating of other ingredients within the mouth
59
Nystatin in magic mouthwash * absorbed? * Not appropriate for? * Use if ?
* 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
polyenes
nystatin and amphotericin B
61
Corticosteroids in magic mouth wash * names * Reduce * Limit * Reduce what symptoms * Limited evidence for?
* Hydrocortisone, dexamethasone, betamethasone, beclomethasone * Reduce inflammatory process * Limit pain sensation * Reduce swelling, erythema * Limited evidence for use / controversial
62
Pain/Oral Irritation agents of magic mouth wash
* 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
Oral Mucocutaneous Candidiasis agents of magic mouthwash
* Diphenhydramine - analgesic * Nystatin - antifungal * Magnesium hydroxide/ aluminum hydroxide - vehicle * Corticosteroid – in an opportunistic infection??? NO
64
Administration of magic mouth wash
* 2 tablespoons (30mL) every four to six hours * Swish and spit to avoid systemic side effects * Pharyngeal involvement?
65
Side Effects of magic mouth wash
* 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
Evidence for magic mouth wash
The evidence is limited and controversial
67
why is magic mouthwash controversial
Controversial because of Formulation Heterogeneity * Diphenhydramine for all indications * Maalox® for all indications * Lidocaine for pain * Nystatin for candidiasis * Avoid steroids
68
Binds/inhibits squalene epoxidase * Squalene precursors build up and are also toxic aiding toxicity * Requires actively growing fungi
»Terbinafine (Lamisil oral or topical) and Naftifine (Naftin) moa
69
azoles moa
70
Miconazole, Clotrimazole: Not taken systemically Clotrimazole & miconazole oral formulations less cariogenic; better tolerated vs Nystatin.
First Generation Azoles
71
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.
Miconazole (Oravig) dosage
72
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
Clotrimazole (Mycelex) dosage
73
Fluconazole (Diflucan), itraconazole, voriconazole, posaconazole, isavuconazole
Second Generation Azole: Triazoles
74
second gen azole
Fluconazole (Diflucan) * absorb * t1/2 * excretion where * ddi * preg category *
75
VORICONAZOLE (VfendTM
76
POSACONAZOLE (Noxafil™)
77
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
Amphotericin B (Liposomal)
78
* Apthous stomatitis * Recurrent aphthous ulcers (RAU) * Chemo-induced oral mucositis
Magic Mouthwash * Common Indications:
79
* Antihistamine / reduce inflammatory process * Limit pain sensation * Reduce swelling, erythema
Diphenhydramine (Benadryl)
80
* 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
Viscous Lidocaine * Relieves? * IMPORTANT * Use how much? * action
81
* Antacid – Maalox and Mylanta * Primarily used as vehicle to enhance coating of other ingredients within the mouth
Magnesium Hydroxide / Aluminum Hydroxide * role * Primarily used as?
82
* 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
Nystatin in magic mouthwash * absorbed? * Not appropriate for? * Use if ?
83
nystatin and amphotericin B
polyenes
84
* Hydrocortisone, dexamethasone, betamethasone, beclomethasone * Reduce inflammatory process * Limit pain sensation * Reduce swelling, erythema * Limited evidence for use / controversial
Corticosteroids in magic mouth wash * names * Reduce * Limit * Reduce what symptoms * Limited evidence for?
85
* 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
Pain/Oral Irritation agents of magic mouth wash
86
* Diphenhydramine - analgesic * Nystatin - antifungal * Magnesium hydroxide/ aluminum hydroxide - vehicle * Corticosteroid – in an opportunistic infection??? NO
Oral Mucocutaneous Candidiasis agents of magic mouthwash
87
# angular chelitis rx
clotrimazole ointment BID 1-3wks
88
which antifungal has the lowest chance of ddi
nystatin
89
which antifungal has the highest chance of ddi
fluconazole

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