Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PHRM 111 – IID > IID 19 and 22: Antifungals > Flashcards

IID 19 and 22: Antifungals Flashcards

(81 cards)

Start Studying
1
Q

What are the primary pathogens?

A
  • Histoplasma capsulatum – dimorphic fungi
  • Coccidioides immitis – dimorphic fungi
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the opportunistic pathogens?

A
  • Candida
  • Aspergillus
  • Cryptococcus
  • Pneumocystis
  • Rhizopus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the classes of dermatophytes?

A
  • Trichophyton
  • Microsporum
  • Epidermophyton
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are some common dermatophytoses infections?

A
  • Tinea pedis (athlete’s foot)
  • Tinea cruris (jock itch)
  • Onychomycosis (fungal nail infections)
  • Tinea corporis (ringworm)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do dermatophytoses do?

A

produce localized infections of keratinized, non-viable tissues (stratum corneum, nails, hair)

  • most minor illnesses are self-limiting if cells eliminated quickly
  • can become chronic in tissues that turnover slowly (ie. toenails, feet soles)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 7 types of antifungal drugs?

A
  • polyenes (AmB)
  • azoles
  • echinocandin (caspofungin)
  • allylamides
  • griseofluvin
  • orotomides
  • flucytosine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the preferred treatment for cutaneous fungal infections?

A

topical agents

  • low risk of ADRs, localized at site of application
  • very poorly absorbed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the topical antifungals that are reformulations of systemic drugs and what is their MOA?

A
  • topical polyenes (nystatin) – bind to ergosterol
  • topical azoles (clotrimazole, econazole) – inhibit ergosterol synthesis
  • topical allylamines (terbinafine, naftifine) – inhibit ergosterol synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the exclusively topical antifungals and what is their MOA?

A
  • ciclopirox olanine – inhibit cellular transport
  • tolnaftate – inhibit ergosterol synthesis
  • undecylenic acid – unknown
  • tavaborole – inhibit tRNA(leu) synthesis
  • selenium disulphide – inhibit mitosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Class I: Polyenes

A
  • amphotericin B (fungizone)
  • nystatin (mycostatin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Polyenes – Amphotericin B (Fungizone®)

A

polyene macrolide antibiotic produced by Streptomyces nodosus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Polyenes – Amphotericin B (Fungizone®)

MOA

A

fungicidal

  • binds to ergosterol in fungal cell membrane
  • forms pores in membrane, altering cell permeability
  • results in leakage of ions and macromolecules, changing osmolarity and eventually resulting in cell death
  • selectivity results from higher affinity for ergosterol than cholesterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Polyenes – Amphotericin B (Fungizone®)

ADME

A
  • nearly insoluble in water, not absorbed on oral administration
  • formulated for IV administration by complexing with deoxycholate
  • widely distributed except to CSF
  • binds to plasma proteins, accumulates in tissues
  • slow elimination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Polyenes – Amphotericin B (Fungizone®)

Antifungal Spectrum

A
  • most broad spectrum IV antifungal available
  • active against almost all common invasive fungi (including many Candida and some Aspergillis species) and endemic fungi
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Polyenes – Amphotericin B (Fungizone®)

Therapeutic Uses

A
  • mainstay for treatment of serious systemic fungal infections – wide spectrum of antifungal activity, low cost, development of resistance during therapy uncommon
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Polyenes – Amphotericin B (Fungizone®)

Limitations

A
  • lack of oral bioavailability is major roadblock – new PO formulation under development
  • development of nephrotoxicity is major limitation to use
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Polyenes – Amphotericin B (Fungizone®)

Adverse Effects

A

due to interaction of AmB in mammalian cell membranes

  • nephrotoxicity – reversible or irreversible
  • infusion reactions – occur in most patients, fever and chills, end spontaneously in hours (reduce severity by slow infusion rate, reduce dose, pre-medication with acetaminophen, antihistamines, and/or corticosteroids)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Nystatin (Mycostatin®)

A

polyene macrolide antifungal agent produced by Streptomyces noursei

  • too toxic for parenteral administration
  • well-tolerated on topical use – available in creams/ointments for use in mucocutaneous Candida infections (particularly oropharyngeal thrush, vaginal candidiasis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Class II: Azoles

A

synthetic compounds containing 5-membered azole ring

  • 1st gen: imidazole – ketoconazole (nizoral)
  • 2nd gen: triazole 1 – fluconazole (diflucan)
  • 2nd gen: triazole 2 – itraconazole (sporanax)
  • 3rd gen: triazole 3 – vorticonazole (vfend)
  • 3rd gen: triazole 4 – posaconazole (spriafil)
  • 3rd gen: triazole 5 – isavuconazole (cresemba)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Class II: Azoles

MOA

A
  • fungicidal
  • inhibit fungal sterol-14a-demethylase (CYP51) – ergosterol synthesis
  • production and build-up of toxic alternate sterol products – membrane poisoning
  • resistance (rare) is increasing mainly due to increased production or altered structure of sterol-14a-demethylase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Class II: Azoles

ADME

A
  • major family of orally available antifungal agent
  • bioavailability depends on individual formulation
  • CNS availability differs for individual agent (implications on treatment of CNS infections)
  • most azoles undergo extensive hepatic metabolism by hepatic enzymes before renal or GI elimination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Class II: Azoles

Therapeutic Uses

A
  • important alternative to AmB in treatment of systemic fungal infections
  • spectrum of antifungal activities is congener
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Class II: Azoles

Adverse Effects

A
  • relatively non-toxic
  • most common is mild GI irritation
  • may cause elevation of liver enzymes, but rarely hepatitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Class II: Azoles

Drug Interactions

A
  • common due to inhibition of mammalian CYP-P450s
  • some congeners are likely teratogenic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Class II: Azoles Drug Resistance Mechanisms
- increase drug efflux - mutations of drug target (Erg11) - increase expression of Erg11 - replacement of ergosterol with 14α-methylfecosterol (cross-resistance with polyene)
26
1st Gen: Imidazole – Ketoconazole (Nizoral)
- wide spectrum of adverse effects and drug interactions due to inhibition of mammalian cytochrome P450s (higher than all triazoles) - largely replaced by newer triazoles for systemic use – only imidazole still used systemically - used topically for superficial fungal infection
27
2nd Gen: Triazole 1 – Fluconazole (Diflucan)
- higher oral bioavailability, administered IV, excellent CNS penetration - lowest adverse effects - narrowest antifungal spectrum, but effective against many Candida species and cryptococcal meningitis
28
2nd Gen: Triazole 2 – Itraconazole (Sporanax)
- limited oral bioavailability, absorption increased by food and low gastric pH - penetrates poorly into CNS - large number of drug interactions (ie. ↓ metabolism of warfarin, omeprazole, digoxin) - broader spectrum than fluconazole, used in systemic infections by histoplasma and blastomyce - may be used in dermtaophytoses (including onychomycosis)
29
3rd Gen: Triazole 3 – Voriconazole (Vfend)
- well absorbed orally - may result in hepatotoxicity, transient visual disturbances, skin rash - likely teratogenic, contraindicated in pregnant women - smaller number of drug interactions, but includes ↓ metabolism of phenytoin, warfarin, omeprazole - broad spectrum of antifungal activity, including invasive Aspergillis (more effective and better tolerated than AmB) and as salvage therapy for infections from Scedosporium and Fusarium species
30
3rd Gen: Triazole 4 – Posaconazole (Spriafil)
- well absorbed orally - may result in hepatotoxicity, ↑ risk of arrhythmia - drug interactions with CYP3A4 and other P450 enzyme substrates (> fluconazole and voriconazole, < itraconazole) - approved for prophylaxis against Candida and Aspergillus in immunocompromised (hematological stem cell transplant recipient w/ GVHD and patients of hematological malignancy) individual at risk of systemic infections - broadest spectrum triazole
31
3rd Gen: Triazole 5 – Isavuconazole (Cresemba)
- oral or IV - well absorbed orally w/ 98% bioavailability - may result in hepatotoxicity and GI effects - drug interactions with CYP3A4 and other P450 enzyme substrates (drug interactions profile is less than posaconazole, but more than fluconazole or voriconazole) - approved for invasive aspergillosis and mucomycosis
32
What is the order of triazole interactions with CYP-P450?
fluconazole < isavuconazole < posaconazole < voriconazole < itraconazole
33
What are the topical azoles?
- include all imidazoles in addition to ketoconazole – clotrimazole, econazole, miconazole, oxiconazole - efinaconazole is the only triazole in class - formulations include cream, ointment, spray, and topical solutions - widespread use as topical antifungals in: mucocutaneous candidiasis (vaginal candidiasis, oropharyngeal thrush), dermatophyte infections of skin (ie. ringworm), nails (onychomycosis)
34
Class III: Echinocandins
semi-synthetic cyclic peptide linked to long chain fatty acid (lipopeptides), newest class - caspofungin - micafungin (mycamine) - anidulafungin (eraxis) - rezafungin (CD101)
35
Class III: Echinocandins MOA
fungicidal - inhibit FKS-1 subunit of 𝛽(1,3) glucan synthase - depletion of 𝛽(1,3) glucans in fungal cell wall leads to osmotic stress and fungal cell death - selective because 𝛽(1,3) glucan is unique to fungal cells
36
Class III: Echinocandins Spectrum
limited to Candida and Aspergillus species
37
Class III: Echinocandins Drug Resistance
low incidences, but increasingly observed mutations of drug target FKS (𝛽(1,3) glucan synthase)
38
Caspofungin ADME
- very poorly absorbed after oral administration - only available for IV administration - extensive hepatic and non-enzymatic biotransformation - limited distribution to CNS
39
Caspofungin Adverse Effects
- generally well-tolerated - minor GI upset and flushing
40
Caspofungin Therapeutic Uses
- active against mucocutaneous and systemic candidiasis - approved for use in patients with invasive Aspergillis infection who failed to respond to AmB - not useful in meningitis or endophthalmitis
41
Micafungin (Mycamine)
- IV administration, adverse effects rare but may include immunosuppression - extensive hepatic enzymes dependent biotransformation - increase serum levels of nifedipine (calcium channel blocker, use against hypertension) - approved for use against Candidiasis
42
Anidulafungin (Eraxis)
- IV, minimal adverse effects - metabolism is largely non-enzymatic (spontaneous degradation to open-ring peptide) - no significant drug interactions - approved for use against Candidiasis
43
Rezafungin (CD101)
- newest echinocandin - topical development hampered by low chemical solubility and unstable chemical structures - long t1/2 and superior stability, ideal properties to overcome physical limitations of other echinocandins - approved against invasive candidiasis as systemic agent (but not in Canada), clinical trials as topical agent are ongoing
44
Class IV: Allylamine
highly lipophilic synthetic molecule - terbinafine (lamisil) - topical (terbinafine, naftifine, butenafine)
45
Class IV: Allylamine MOA
fungicidal and fungistatic in some Candida species that can tolerate high squalene levels - inhibits squalene epoxidase - leads to accumulation of squalene (toxic) and disruption of ergosterol synthesis – *acts in step of ergosterol synthesis before azoles*
46
Terbinafine (Lamasil) ADME
- orally available - biotransformation mediated by multiple CYP-P450 enzymes - accumulates in skin and nails
47
Terbinafine (Lamasil) Adverse Effects
- well-tolerated, GI upset and headache occur rarely - rarely causes idiopathic liver toxicity – patients at risk of hepatotoxicity should have liver enzymes monitored
48
Terbinafine (Lamasil) Therapeutic Uses
- available in oral formulation for use in treatment of dermatophytoses, particularly onychomycosis - treatment for 6 weeks (fingernails) to 12 weeks (toenails) results in up to 80% cure rate - available as cream, for topical use in skin infections (ie. ringworm, jock itch)
49
Topical (Terbinafine, Naftifine, Butenafine)
treatment of tinea infections
50
Topical (Terbinafine, Naftifine, Butenafine)
- inhibit squalene epoxidase - fungicidal against dermatophytes - fungistatic against Candida
51
Other Systemic Antifungal Agents
- flucytosine (ancobon) - griseofulvin (grifulvin)
52
Flucytosine (Ancobon) MOA
- fungicidal - anti-metabolite, fluorinated pyrimidine analog - metabolized in fungal cells to 5-FU and interfere with DNA and RNA metabolism
53
Flucytosine (Ancobon) Adverse Effects
bone marrow, liver, and renal toxicities, which could be life-threatening
54
Flucytosine (Ancobon) Therapeutic Uses
only use in systemic treatment of severe candidiasis or cryptococcal meningitis, in combo with AmB
55
Griseofulvin (Grifulvin) MOA
- oral fungistatic compound - inhibits mitotic spindle assembly - binds to keratin in newly forming skin, protecting from infection - must be administered for 2-6 weeks (skin and hair) or up to 18 months (nails)
56
Griseofulvin (Grifulvin) Adverse Effects
headache, hepatitis, increases metabolism of warfarin and phenobarbital
57
Griseofulvin (Grifulvin) Therapeutic Uses
- only use in systemic treatment of mycosis of nail and keratinized tissues - largely replaced by new antifungals (ie. terbinafine)
58
Additional Topical Antifungal Drugs for Cutaneous Infections
- ciclopirox olamine (loprox) - ciclopirox 8% nail lacquer (penlac) - tolnaftate (tinactin) - undecylenic acid (desenex) - tavaborole (kerydin)
59
Ciclopirox Olamine (Loprox) MOA
not clear, may inhibit fungal intracellular transport - broad spectrum fungicidal activity - antibacterial and anti-inflammatory activity - available as cream or lotion for tinea infections and cutaneous Candidiasis
60
Ciclopirox 8% Nail Lacquer (Penlac)
- for topical treatment of mild to moderate fungal nail infections - but poor evidence against onchyomycosis
61
Tolnaftate (Tinactin) MOA
inhibits squalene epoxidase (and therefore ergosterol synthesis), targeting same enzyme as allylamines - effective in treatment of most cutaneous mycoses (fungicidal) - not effective in those caused by Candida (fungistatic due to tolerance against squalene accumulations)
62
Undecylenic Acid (Desenex) MOA
unknown - present in human sweats - fungistatic - active against a variety of fungi - used in treatment of various dermatophytoses (ie. Tinea pedis)
63
Tavaborole (Kerydin) MOA
inhibits fungal tRNA(leu) synthetase (and therefore inhibits protein synthesis) - effective in treatment of onychomycoses (fungicidal) due to agent’s ability to penetrate nail bed - effective fungicidal activity within 5 days of topical applications
64
Nystatin
- mucocutaneous Candida
65
Topical Azoles
- mucocutaneous Candida - dermatophyte skin infections - onychomycosis
66
Ciclopirox Olamine
- mucocutaneous Candida - dermatophyte skin infections - onychomycosis
67
Tolnaftate
- dermatophyte skin infections - onychomycosis
68
Topical Allylamines
- dermatophyte skin infections - onychomycosis
69
Undecylenic Acid
- dermatophyte skin infections - onychomycosis
70
Tavaborole
- onychomycosis
71
Polyenes – Systemic (1)
amphotericin B
72
Polyenes – Topical (1)
nystatin
73
Azoles – Systemic (6)
- ketoconazole - itraconazole - fluconazole - voriconazole - posaconazole - isavuconazole
74
Azoles – Topical (6)
- ketoconazole - econazole - clotrimazole - oxiconazole - miconazole - efinaconazole
75
Echinocandin – Systemic (3)
- caspofungin - micafungin - anidulafungin
76
Echinocandin – Topical
none
77
Allylamines – Systemic (1)
terbinafine
78
Allylamines – Topical (3)
- terbinafine - naftifine - butenafine
79
Miscellaneous – Systemic (1)
griseofulvin
80
Miscellaneous – Topical (4)
- ciclopirox olamine - tolnaftate - undecylenic acid - tavaborole
81
What are some common fungi species?
- Saccharomyces cerevisiae - Candida albicans - Trichophyton rubrum - Microsporum gypseum

PHRM 111 – IID (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions