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DWT Exam 4 > Pharmacology - Antifungal > Flashcards

Pharmacology - Antifungal Flashcards

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1
Q

Antifungal drugs

A

Griseofulvin
Amphotericin B
Azole antifungals **
Terbinafine

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2
Q

Antiviral drugs

A

Antiherpetic drugs
Anti-influenza drugs

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3
Q

Diagnosis of fungal diseases

A

Difficult to diagnose
Difficult to treat - fungi reaches highly protected sites that few drugs can reach
Treatment is long & expensive

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4
Q

Factors for increased fungal incidence

A

Immunosuppression
Radiation therapy
Chemotherapy
Prolonged corticosteroid use

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5
Q

Mechanism and action of griseofulvin

A

Dermatophytes - microsporum, Trichophyton
Inhibits mitosis of fungal cells, fungalstatic

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6
Q

What route of absorption is ideal for griseofulvin?

A

Oral, enhanced w meal - lipophilic drug
Micronized (25-70%)
Ultramicronized (100%)
Formulation effects dosing / absorption

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7
Q

Distribution of griseofulvin

A

To skin, deposits in stratum corneum by 48-72 hrs, persists for weeks = fewer doses required

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8
Q

Adverse effects of griseofulvin
Cats & horses

A

Cats: bone marrow suppression, esp in FeLv
Teratogenic in pregnant animals = no use
Horses: teratogenic in early pregnancy

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9
Q

Amphotericin B

A

Polyene antifungal, reserved for severe illness

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10
Q

Mechanism of Amphotericin B

A

Binds to sterols in fungal cells - toxicity binding to cholesterol
Cell membrane = more permeable
Fungicidal

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11
Q

Common adverse effects in Amphotericin B

A

Renal injury - always monitor function during administration
Acute injury - altered blood flow, azotemia
Chronic (cumulative) injury - ischemia, cell death

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12
Q

Less common adverse effects of Amphotericin b

A

Fever
Thrombophlebitis
Nausea, vomiting, anorexia
Anemia

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13
Q

How to decrease Amphotericin B toxicity

A

Fluid pretreatment
Slow IV infusion
Liposomal formulations

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14
Q

Drug interactions with Amphotericin b
- flucytosine

A

Synergistic
Treat refractory CNS cryptococcus infections
Combo can decrease dose/ toxicity of Amphotericin

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15
Q

Drug interactions with Amphotericin b
- azole

A

Treat w ampB first, allow switching to azole for out of hospital treatment/recovery use
XX using azole first, binds/alters receptor site

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16
Q

Azole antifungal drugs mechanism
Inhibits what enzyme? And what synthesis?

A

Inhibit 14alpha demethylase
Synthesis of fungal cell sterols, inhibit ergosterol synthesis
Fungistatic

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17
Q

Common ADRs of azole drugs

A

Hepatotoxicity, not safe during pregnancy

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18
Q

Older azole drugs

A

Imidazoles
- ketoconazole: systemic

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19
Q

Newer azole drugs

A

Triazoles
- itraconazole
- fluconazole
- voriconazole
(Posaconazole)**

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20
Q

Dimorphic fungi spectrum drugs

A

Blastomyces
Histoplasma
Cryptococcus
Sporothrix
(Most lipophilic will treat)

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21
Q

Dermatophytes spectrum drugs

A

Filamentous fungi (+/-)
Aspergillus
Fusarium
Depends on drugs

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22
Q

PK of ketoconazole

A

Oral absorption enhanced by food
Inhibited by anti acids
Not absorbed in horses

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23
Q

AE of ketoconazole

A

Cheapest & most adverse effects
Nausea, vomiting, diarrhea
Heptotoxicosis
Cataracts
Fetal death

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24
Q

Adverse effects mechanism of ketoconazole
Inhibits? Decreases?

A

Inhibits steroid synthesis (CYP450 mediated)
Decreases testosterone & cortisol
Short term management of Cushings disease

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25
Q

ketoconazole inhibits which 2 bodily functions?
And can interact with what drug in what species?

A

Inhibits CYP450 enzymes (metabolism of drugs)
Cyclosporine A in dog/cat
Inhibit p-glycoprotein efflux pumps (increased concentration of drugs in CNS, eye, plasma)

26
Q

Triazoles

A

Itraconazole, fluconazole, voriconazole

27
Q

Itra, flu & vori

A

Better tolerated than ketoconazole
Less cyp 450/p-glycoprotein inhibition
Itra>vori>flu

28
Q

Itraconazole adverse effects

A

Hepatic - increased liver enzymes, hepatotoxicosis
GI: anorexia, vomiting
Congestive heart failure (common in people)

29
Q

PK of itraconazole

A

Extremely lipophilic, concentrates in tissues/skin for 2-4 weeks, high protein binding
Absorption increased by food, decreased in horses
pH dependent - for cats & horses

30
Q

Fluconazole mechanism

A

Hydrophilic, low protein binding
High concentrations: urine, CFS, aqueous humor
High oral absorption (even in horses)

31
Q

Fluconazole adverse effects

A

Minimal, increased hepatic enzymes, prolonged recovery (ketamine/midazolam)

32
Q

Fluconazole formulations

A

Tablets, suspension, injection

33
Q

Vorizconazole

A

More activity against fursarium
Fungicidal against aspergillus

34
Q

Voriconazole absorption

A

> 100% oral absorption
Excellent penetration into CNS & eye
Dogs, horses, birds
NO CATS

35
Q

Possible toxicity of voriconazole in cats

A

Ataxia - paraplegia of hind limbs
Mydriasis - decreased PLR
Hypokalemia - arrhythmias
Inappetance - lethargy, weight loss
Azotemia - cutaneous drug reaction, ataxia, paresis
Longer dosing

36
Q

What drug is an allyamine antifungal?

A

Terbinafine
Inhibits ergosterol synthesis by inhibiting squalene epoxidase
Fungicidal

37
Q

Terbinafine spectrum of activity (3/2/1~)

A

Dermatophytes
Yeast
Dimorphic
Some filamentous fungi
Some aspergillus strains
No fusarium
Combo therapy for toxoplasma (Protozoa)

38
Q

Absorption of Terbinafine

A

Oral absorption, concentrates in hair/skin 75x those in plasma by 12 days

39
Q

Adverse effects of Terbinafine
Inhibition or none? In what species? What are more rare AE?

A

No inhibition of cyp450 enzymes
Cats: vomiting during treatment , Intense facial puritis, Skin reactions
Rare hepatitis & lost of taste
Not teratogenic

40
Q

Antiviral drugs use

A

Limited, viral infections are self limiting
Judicious use

41
Q

What kind of virus is used for nucleoside analogs?

A

Antihepetic drugs, prodrugs
Better bioavailability

42
Q

Valacyclovir used for what virus?

A

Equine herpesvirus myelitis
Found to decrease shedding, judicious use as virus is neurological and is fatal

43
Q

Types of inhibitors in anti-influenza drugs

A

Adamantane inhibitors
Amantadine & rimantadine
Neuraminidase inhibitors
Oseltamsvir

44
Q

Which drug has more activity against fursarium?

A

Voriconazole

45
Q

What mycolic fungi does voriconazole have more activity against?

A

Fursarium

46
Q

Which fungi is voriconazole “cidal” against?

A

Aspergillus

47
Q

Which azole drug is more lipophilic than fluconazole?

A

Voriconazole

48
Q

Fluconazole varies from voriconazole how?

A

Voriconazole is more lipophilic than fluconazole

49
Q

What’s the relative protein binding of voriconazole?

A

Intermediate protein binding

50
Q

Which azole is more water soluble than itraconazole / ketoconazole?

A

Viroconazole

51
Q

Viroconazole is more ________ than which azole drugs?

A

Water soluble
Itraconazole/ketoconazole

52
Q

Relative protein binding in itraconazole

A

High protein binding

53
Q

How long does itraconazole stay concentrated in patients?

A

2-4 weeks in tissues

54
Q

Which azole drug is hydrophilic?

A

Fluconazole

55
Q

Relative protein binding of fluconazole?

A

Low protein binding

56
Q

What antifungal drugs have “cidal” properties?

A

Amphotericin B
Terabinafine
Viroconazole (against aspergillus)

57
Q

Which antifungal drugs have “static” properties?

A

Azoles
Griseofulvin

58
Q

Which azole has the least amount of ADE ?

A

Fluconazole

59
Q

Ataxia presents how? And is a possible adverse affect in what drug?

A

Paraplegia of hind limbs
Viroconazole

60
Q

Mydriasis is caused by what PK and from what drug?

A

Decreased PLR
Viroconazole

61
Q

Inappetance presented as _______ is caused by what drug?

A

Presented as lethargy and weight loss
Viroconazole

62
Q

Azotemia cause by _________ can lead to _______?

A

Viroconazole
Cutaneous drug reaction, ataxia, paresis

DWT Exam 4 (3 decks)

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