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PHA 411 > Antifungals > Flashcards

Antifungals Flashcards

1
Q

What are antifungals?

A

Antifungal drugs are chemical agents that selectively
eliminate fungal pathogens from the host with minimal
toxicity and are used for the treatment of fungal
infections (mycoses) in animals.

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2
Q

What are fungi?

A

Fungi are eukaryotic unicellular or
multicellular organisms that contain chitin in their
cell wall and include microorganisms (yeasts,
dermatophytes and molds) as well as macroorganisms
(mushrooms)

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3
Q

Types of fungi based on feeding

A

Saprophytic fungi: feed on dead tissues

Parasitic fungi: feed on living tissues

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4
Q

What is fungal infection of the nails called?

A

Onychomycosis

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5
Q

What are the types of onychomycosis?

A
  • White superficial onychomycosis
  • Proximal subungual onychomycosis
  • Distal subungual onychomycosis
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6
Q

What are dermatophytoses?

A

Fungal
infections of skin and hair

AKA Tinea

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7
Q

What is Tinea pedis?

A

athletes’ foot

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8
Q

What is tinea cruris?

A

Fungal infection of the groin

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9
Q

What is tinea capitis?

A

Fungal infection of the scalp

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10
Q

What is a tineal infection of the nails called?

A

Tinea unguium

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11
Q

What is tinea mannum?

A

Fungal infection of the hand

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12
Q

What is mucosamycosis?

A

Candida infection of body mucosa

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13
Q

What organism causes mucosamycoses?

A

Candida
albicans

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14
Q

Examples of mucosamycoses

A
  • Oral candidiasis: mouth
  • Vaginal candidiasis: vaginal mucosa
  • Candida intertrigo: skin folds- groin, armpits, buttocks
  • Candida interdigitalis: between fingers, foot digits
  • Candida onychomycosis: nail
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15
Q

What are the causative organisms of Onychomycosis and Dermatophytosis?

A

Epidermophyton floccosum, Trichophyton rubrum or
Microsporum canis

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16
Q

What iis the point of origin of systemic fungal pathogens?

A

The lungs

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17
Q

Types of systemic fungal infections

A
  • Aspergillosis
  • Coccidioidomycosis
  • Cryptococcosis
  • Histoplasmosis
  • Paracoccidioidomycosis
  • Pneumocystosis
  • Sporotrichosis
  • Cryptosporidiosis
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18
Q

Cause of Aspergillosis

A

Aspergillus fumigatus.

Affects skin and lungs

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19
Q

Cause of Coccidioidomycosis

A

Coccidioides
immitis.

Affects lung,
skin, and joints

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20
Q

Cause of Cryptococcosis

A

Cryptococcus
neoformans.

Affects lung, brain and
skin and may become disseminated

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21
Q

Cause of Histoplasmosis

A

Histoplasma
capsulatum.

Affects primarily the
lung but may be disseminated.

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22
Q

Cause of Paracoccidioidomycosis

A

Paracoccidioides brasiliensis.

Affects lungs, mouth and skin
or disseminate

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23
Q

Cause of Pneumocystosis

A

Pneumocystis
carinii/jirovecii.

Affects lung and skin and may
become disseminate

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24
Q

Cause of Sporotrichosis

A

Sporothrix schenckii.

Affects
mainly the skin.

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25
Q

Causes of Cryptosporidiosis

A

Cryptosporidium hominis, Cryptosporidium parvum, and Cryptosporidium
meleagridis

Mixed infection is
possible

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26
Q

Cryptosporidiosis is an intestinal infection caused by ingesting food or water contaminated with infected faeces.

True or false

A

True

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27
Q

What are the risk factors for mycoses?

A
  1. Excessive use of antibiotics
  2. Steroid treatments
  3. HIV/AIDS infection
  4. Cancer chemotherapy
  5. Very old and very young people
  6. Diabetes
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28
Q

Classes of antifungal agents

A

(1) The Polyene Antifungals
(2) Azole antifungals
(3) Allylamine
(4) Echinocandins
(5) Antimetabolite
(6) Antimitotics

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29
Q

What are polyene antifungals?

A

They are macrocyclic molecules with multiple double bonds and a heavily hydroxylated region opposite the conjugated system and a mycosamine group (an aminoglycoside) often attached to the molecule.

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30
Q

What is the source of polyene antifungals?

A

Streptomyces specie

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31
Q

Examples of polyene antifungals

A

(1) amphotericin B
(2) nystatin
(3)
candicidin
(4) rimocidin
(5) fillipin
(6) natamycin
(pimaricin)
(7) hamycin

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32
Q

Mechanism of action of polyene antifungals

A

The polyene antifungals cause death of fungi by binding to ergosterol, the principal sterol in
their cell membrane, thereby causing formation of pores on the membrane and leakage of intracellular components such as
monovalent ions (k+, Na+, H+ , Cl-), enzymes and other small organic molecules.

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33
Q

Why are human cells less susceptible to the effects of polyene antifungals?

A

Because their
sterol component is cholesterol and not ergosterol.

Some polyene antifungals such as amphotericin B and filipin still
bind to cholesterol at therapeutic doses and this may account
for their side effects.

34
Q

Uses of Amphotericin B

A

Due to severe ADR, its use is limited to severe systemic fungal infection such as
Aspergillosis, blastomycoses, cryptococcosis,
coccidioidomycosis, paracoccidioidomycoses, histoplamosis etc.

It is used IV

35
Q

What species are resistant to amphotericin B

A

Pseudaschellaria boydii, Fusarium
spp, Trichosporon spp, Candida lusitaniae and Candida
guillermondii

36
Q

Adverse effects of Amphotericin B

A

Phlebitis at site of infusion,
chills,
liver
damage,
hearing loss,
visual impairment,
bone
marrow toxicity,
cardiac arrest,
rash,
renal toxicity

37
Q

How does Amphotericin B cause renal toxicity?

A

Suppression of
glomerular filtration

38
Q

How is renal toxicity caused by Amphotericin B countered?

A

Administration of sodium chloride

39
Q

Uses of Nystatin

A

Only for oral, vaginal and GIT
candidiasis.

40
Q

Uses of Natamycin

A

Superficial fungal infections (both
yeasts and mold) of the eye.

41
Q

What are Azole antifungals?

A

Antifungals possessing the azole ring in their chemical structure

42
Q

Classes of Azole antifungals

A

Imidazoles,
Triazoles
Thiazoles

43
Q

Examples of Imidazoles

A

Clotrimazole
Ketoconazole
Butoconazole
Isoconazole
Econazole
Bifonazole

44
Q

Examples of triazoles

A

Fluconazole
Terconazole
Hexaconazole
Albaconazole
Itraconazole
Ravuconazole

45
Q

Examples of thiazoles

A

Abafungin

46
Q

Mechanism of action of azole antifungals

A

Besides abafungin, the azole
block the synthesis of ergosterol by inhibiting the enzyme lanosterol -14 alpha – demethylase, which is
necessary for the conversion of lanosterol to ergosterol.

This leads to distruption of fungal membrane’s structure and functions and inhibition of fungal growth.

47
Q

Mechanism of action of abafungin

A

Inhibits fungal sterol
24c-methyl transferase

48
Q

Abafungin has antibacterial properties.

True or false

A

True

49
Q

Uses of Imidazoles

A

They are mainly
administered topically in pessaries, ovules, solutions, creams or shampoo for the treatment of candidiasis and dermatophytosis

50
Q

Uses of ketoconazole

A
  1. It is applied topically for the treatment of candidiasis and dermatophytosis
  2. It is administered
    systemically by mouth for the treatment of
    blastomycosis and other mycoses
51
Q

Ketoconazole is effective agains aspergillosis.

True or false

A

False

52
Q

Uses of clotrimazole

A
  1. It is applied topically for the treatment of candidiasis and dermatophytosis
  2. It is also used in ear drops for the
    treatment of ear infections.
52
Q

Uses of triazoles

A
  1. The triazoles have replaced amphotericin B in
    the treatment of systemic mycoses.
  2. It is also
    used routinely to treat candidemia,
    cryptococcosis and coccidioidomycosis.
53
Q

Uses of fluconazole

A

Fluconazole is effective in a single dose of
150mg for vaginal candidiasis

54
Q

Uses of itraconazole

A

Itraconazole is effective in the treatment of blastomycosis, coccidioidomycosis, aspergillosis,
cryptococcosis, histoplasmosis and sporotrichosis.

55
Q

Adverse effects of triazoles

A

Nausea and vomiting
Liver toxicity

56
Q

What are the contraindications of ketoconazole?

A

Alcohol and antimetabolite antifungals

57
Q

What are allylamines?

A

An allylamine is an organic compound, a colorless liquid and the simplest stable unsaturated amine

58
Q

Examples of allylamines

A

Butenafine Amorolfine Naftifine Terbinafine

B-A-N-T

59
Q

Mechanism of action of allylamines

A

They block ergosterol synthesis through inhibition of the enzyme squalene epoxidase, which converts squalene to squalene epoxide, which is converted to lanosterol.

60
Q

Adverse effects of terbinafine

A

liver toxicity, myalgia, skin rash, GIT disturbance, visual disturbance, taste disturbance, insomnia, depression, headache, dizziness and blood dyscrasia.

60
Q

Uses of terbinafine

A
  1. Terbinafine is mainly effective against the dermatophytes and is used topically in creams for superficial fungal skin infection such as tinea barbae, tinea corporis, tinea pedis.
  2. It is also used in oral tablet form for treatment of cutaneous fungal skin infection such as onchomychosis (tinea unguium) of toenail and fingernail
61
Q

What are echinocandin antifungals

A

The echinocandins are large lipopeptide
molecules. They are the newest antifungals.

62
Q

Examples of echinocandins

A

Caspofungin, Anidulafungin, and Micafungin

C-A-M

63
Q

Mechanism of action of echinocandins

A

They block the synthesis of Beta (1,3) glucan in fungal cell wall by inhibiting the enzyme beta glucan synthase.

This causes cell wall damage and fungal death.

64
Q

Uses of echinocandins

A
  1. They are administered parenterally in an immunocompromised patient for the treatment of systemic fungal infections, especially invasive candidiasis, candidemia and aspergillosis.
65
Q

Echinocandins are administered orally.

True or false

A

False.

They are not administered orally due to low bioavailability

66
Q

Echinocandins are not active against fusarium spp and cryptococcus neoformans

A

True

67
Q

Adverse effects of echinocandin

A

local phlebitis, fever, haemolysis and abnormal liver function tests

68
Q

Echinocandins have severe adverse effects.

True or False

A

False.

The side effects are mild.

69
Q

Examples of antimetabolite antifungals

A

Flucytosine

70
Q

Mechanism of action of flucytosine

A

Flucytosine is a pyrimidine
analogue that inhibits RNA and DNA synthesis.

In fungal cytoplasm, Flucytosine (5-fluorocytosine) is converted into 5-fluorouracil, which is further converted to 5-fluorouridine
triphosphate and 5-fluorodeoxyuridine
monophosphate.

The latter (5-FM) inhibits RNA synthesis while the former (5-FT) blocks DNA synthesis through inhibition of the enzyme thymidylate synthetase.

71
Q

Uses of flucytosine

A

In combination with amphotericin B, it is the treatment of choice for cryptococcal meningitis

72
Q

Adverse effects of flucytosine

A

hepatic dysfunction,
jaundice, crystalluria, renal failure, headache,
hallucination, hearing loss, parkinsonism, rash,
anaphylaxis and blood dyscrasia

73
Q

Examples of antimitotic antifungals

A

Griseofulvin

74
Q

Mechanism of action of griseofulvin

A

Griseofulvin inhibits
mitosis in fungi by binding to fungal
microtubules and altering the process of mitosis

75
Q

Uses of griseofulvin

A

It is used both in human and animals to treat fungal skin infections (dermatophytosis)

76
Q

Griseofulvin contraindications

A

Griseofulvin is a cytochrome P450 enzyme inducer and is known to reduce the effectiveness of oral contraceptive.

77
Q

Adverse effects of griseofulvin

A

headache, dizziness, nausea,
vomiting, diarrhea, insomnia, skin rash,
antabuse reaction with alcohol

78
Q

Fungicides vs. antifungals

A

While antifungals are used in animals, fungicides are used on plants

PHA 411 (6 decks)

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