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CLIN PHARM > Antifungals & Antivirals > Flashcards

Antifungals & Antivirals Flashcards

1
Q

Which are the factors involved in the therapeutic failure or relapse after antifungal therapy?

A

*Most antifungals are fungistatics, so clearance of the infection relies mainly on the host response
*Poor penetration into the foci of infection
*Intrinsic and acquired resistance to antifungals
*Toxicity
*Inappropriate dosage regimens
*Antifungal culture and susceptibility testing methods not well developed

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2
Q

How long does it take to see full clinical effect of antifungals?

A

?

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3
Q

Which antifungal is considered fungicidal?

A

Amphotericin B

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4
Q

Which antifungal is indicated for treating systemic fungal infections?

A

Amphotericin B

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5
Q

Which antifungal induces hepatic metabolizing enzymes?

A

Griseofulvin

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6
Q

Which antifungal inhibits hepatic metabolizing enzymes?

A

Ketoconazole

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7
Q

Which antifungals are nuclear-directed?

A

Griseofulvin
Flucytosine

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8
Q

Which antifungals are cell membrane directed?

A

The Polyenes
The Azoles
Others

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9
Q

What are the two major classes of antifungals?

A

Cell membrane directed
Nuclear directed

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10
Q

What is the MOA for griseofulvin?

A

Fungistatic
Interacts with microtubules to disrupt the function of the mitotic spindle
(Obvs)

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11
Q

What is the spectrum of activity for griseofulvin?

A

ONLY dermatophytes
(E.g. microsporum, trichophyton, epidermophyton)

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12
Q

Griseofulvin is reported to be ____ and _____.

A

Teratogenic and carcinogenic

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13
Q

_____ has a selective toxicity based on an energy dependent uptake preferentially into fungi vs mammalian cells.

A

Grieseofulvin

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14
Q

Signs of griseofulvin toxicity (8)

A

Diarrhea
Depression
Anorexia
Hepatotoxicity
Bone marrow suppression
Ataxia
Skin rash
Photosensitization

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15
Q

What breeds of cat are especially sensitive to skin rash/photosensitization from griseofulvin toxicity?

A

Persian
Siamese
Abyssinian

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16
Q

Absorption of griseofulvin is markedly enhanced by ____.

A

The presence of a high fat meal

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17
Q

Griseofulvin is highly bound and concentrated in _____.

A

Keratinized cells

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18
Q

Griseofulvin induces ____ enzymes.

A

Hepatic drug metabolizing

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19
Q

Griseofulvin undergoes extensive _____.

A

Inactivation in the liver (first pass effect)

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20
Q

How long does griseofulvin take to reach full effect?

A

Several weeks - total duration of tx 1-4 months

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21
Q

This drug is labeled for use in horses (powder formation) for dermatophytosis.

A

Griseofulvin

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22
Q

Griseofulvin is used for treating ___ in small animals but is being replaced by ___.

A

Dermatophytosis
Azoles

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23
Q

While NOT labeled for use in food animals, this drug has been reported to be effective for treatment of dermatophytes in cattle.

A

griseofulvin

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24
Q

How is withdrawal time determined for use of griseofulvin in food animals?

A

DVM must determine appropriate withdrawal time

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25
Q

What is the MOA for flucytosine?

A

Pro-drug
Once inside the cytoplasm of the fungal organism, it is converted to 5-FU - an antimetabolite that interferes with Nucleic acid synthesis and metabolism, ultimately disrupting protein synthesis.

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26
Q

What is the spectrum of activity for flucytosine?

A

Cryptococcus
Some candida

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27
Q

Resistance to this antifungal develops commonly and quickly, so it’s often used in combination with amphotericin B.

A

Flucytosine
Synergism occurs with amphotericin B

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28
Q

Two toxicities related to flucytosine

A

Bone marrow suppression
Mucous membrane ulceration

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29
Q

Mammalian cells lack _____ and cannot convert the pro-drug 5-FC to its active form 5-FU.

A

Cytosine deaminase

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30
Q

What converts some 5-FC to 5-FU (which is toxic to mammalian cells)?

A

Gastrointestinal flora

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31
Q

What is the MOA of amphotericin B?

A

Fungicidal
Binds to ergosterol to form a transmembrane pore that disrupts membrane function by allowing small molecules to leak through the membrane

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32
Q

What is the spectrum of activity for amphotericin B?

A

Generally utilized only for severe systemic fungal infections such as histoplasma, blastomyces, cryptococcus, sometimes coccidiodes, and other less common fungal infections.

Dermatophytes are NOT susceptible

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33
Q

______ are not susceptible to amphotericin B.

A

Dermatophytes

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34
Q

Development of resistance is infrequent with this antifungal.

A

Amphotericin B

35
Q

What kind of toxicity is common in patients treated with amphotericin B?

A

Nephrotoxicity

36
Q

What are possible reactions related to amphotericin B toxicity?

A

Anaphylactic-like reactions, vomiting, and fever

37
Q

_____ may reduce the occurrence or severity of nephrotoxicity with amphotericin B.

A

Fluid therapy

38
Q

Newer and more expensive formulations of amphotericin B are ____ and greatly reduce the risk of nephrotoxicity.

A

Liposome encapsulated

39
Q

Amphotericin B is available only for ___ use.

A

IV use
Diluted in 5% dextrose

40
Q

Amphotericin B has a ____ plasma half life.

A

LONG
1-2 weeks

41
Q

60% of this antifungal drug is eliminated by urine (causing nephrotoxicity).

A

Amphotericin B

42
Q

Amphotericin B is used in small animals for treating ____.

A

Systemic fungal infections
blastomycosis
Histoplasmosis
Cryptococcus most commonly

43
Q

What is the mechanism of action of ketoconazole?

A

Fungistatic
Inhibits ergosterol synthesis (ergosterol is the primary sterol of fungal cell membranes vs cholesterol in mammalian cell membranes) by inhibiting a CYP450 enzyme (CYP51A)

44
Q

Do not combine amphotericin with ____.

A

Azoles

45
Q

What is the spectrum of activity with ketoconazole?

A

Usually susceptible:
Candida
Malassezia
Dermatophytes

Sometimes susceptible:
Cryptosporidium immitis
Histoplasma capsulatum
Blastomyces dermatidis

46
Q

____ is much safer than amphotericin B.

A

Ketoconazole

47
Q

What are the most common signs of toxicity with ketoconazole?

A

GI upset and hepatotoxicity (esp. in cats)

48
Q

This drug probably contributes to more serious drug interactions than any other drug in dogs.

A

KETOCONAZOLE

49
Q

This antifungal interferes with progesterone and testosterone.

A

ketoconazole

50
Q

Ketoconazole ____ mammalian steroid biosynthesis by inhibiting mammalian CYP enzymes

A

Inhibits

51
Q

Ketoconazole is highly protein bound (>98%) therefore does not distribute well to __.

A

CNS
Prostate
Eye

52
Q

Ketoconazole requires ___ for oral absorption.

A

Acid pH

53
Q

The most common use for ketoconazole in vet med use is for ___ in dogs (topical formulations and systemic administration).

A

Malassezia dermatitis

54
Q

Ketoconazole is used for dermatophytosis in dogs and cats and sometimes as an adjunct treatment for _____.

A

Systemic mycotic infections

55
Q

This drug has better efficacy against Candida, Aspergillus, dermatophytes, and most systemic fungi than ketoconazole.

A

Itraconazole

56
Q

This drug has fewer adverse effects but is more expensive than ketoconazole.

A

Itraconazole

57
Q

Which antifungal penetrates the CNS and urinary tract?

A

Fluconazole

58
Q

Fluconazole does not undergo ____ and is excreted via ____.

A

Metabolism
Urine

59
Q

This antifungal has approximately 100% bioavailability in horses.

A

Fluconazole

60
Q

Which antifungal has the best oral absorption?

A

Fluconazole

61
Q

Oral absorption of which antifungal is independent of pH?

A

Fluconazole

62
Q

Name two topical azole antifungal agents.

A

Clotrimazole
Miconazole

63
Q

Is clotrimazole orally bioavailable?

A

No

64
Q

What are three indications for use of clotrimazole?

A

*Topically for treating nasal aspergillosis in dogs
*Infused into bladder of dogs/cats with fungal candiduria
*Treatment of otitis externa caused by Malassezia pachydermatitis

65
Q

This topical azole antifungal agent undergoes rapid metabolism and would require frequent IV infusions for systemic use.

A

Miconazole

66
Q

Miconazole is indicated for use in treatment of ___.

A

Dermatophytosis in dogs and cats

67
Q

What is the MOA for terbinafine?

A

Inhibits the enzyme squalene epoxidase which results in decreased ergosterol synthesis

68
Q

How is terbinafine used?

A

Topically and systemically for dermatophytosis in dogs and cats

69
Q

High concentrations of this antifungal agent are reached in nail beds, although it takes several months of therapy to achieve results for onychomycosis.

A

Terbinafine

70
Q

Factors involved in therapeutic failure/relapse after antifungal tx:

Most antifungals are ______, therefore clearance of the infection relies mainly on the host response.

A

Fungistatics

71
Q

Factors involved in therapeutic failure/relapse after antifungal tx:

_________ into the foci of infection

A

Poor penetration

72
Q

Factors involved in therapeutic failure/relapse after antifungal tx:

Intrinsic and acquired _____ to antifungal tx

A

Resistance

73
Q

Factors involved in therapeutic failure/relapse after antifungal tx:

_________

A

Toxicity

74
Q

Factors involved in therapeutic failure/relapse after antifungal tx:

_________ dosage regimens

A

Inappropriate
Discontinuation of tx after resolution of clinical signs but not eradication of the infection

75
Q

Factors involved in therapeutic failure/relapse after antifungal tx:

_____ that are not well developed

A

Antifungal culture and susceptibility testing methods

76
Q

Four categories of antiviral agents

A

Neuramidase inhibitors
Assembly inhibitors
Transcription inhibitors
Interferons

77
Q

Name the antiviral agent that is a neuraminidase inhibitor.

A

Oseltamivir

78
Q

Name the antiviral agent that is an assembly inhibitor.

A

Amantadine

79
Q

Name 7 antiviral agents that are transcription inhibitors

A

Idoxurine
Trifluridine
Vidarabine
Acyclovir, Famciclovir, Ganciclovir
Zidovudine (AZT)

80
Q

This antiviral topical medication is used to treat viral infections of the eye, such as herpesvirus-1 in cats.

A

Idoxuridine

81
Q

Unsubstantiated claims have been made about the efficacy of this antiviral drug for reducing the severity of parvovirus infection in dogs.

A

Oseltamivir

82
Q

This antiviral drug has shown benefit in treating feline herpes virus in cats (ocular and respiratory manifestations).

A

Oral famciclovir

83
Q

The FDA has banned the use of this antiviral drug in birds.

A

Zidovudine

84
Q

This antiviral drug shows some evidence for activity against reverse transcriptase enzymes of Feline Immunodeficiency Virus and Feline Leukemia Virus, but is not curative.

A

Zidovudine

CLIN PHARM (13 decks)

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