Pharmacology - Antifungal

Question 1

Antifungal drugs

Answer 1

Griseofulvin
Amphotericin B
Azole antifungals **
Terbinafine

Question 2

Antiviral drugs

Answer 2

Antiherpetic drugs
Anti-influenza drugs

Question 3

Diagnosis of fungal diseases

Answer 3

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

Question 4

Factors for increased fungal incidence

Answer 4

Immunosuppression
Radiation therapy
Chemotherapy
Prolonged corticosteroid use

Question 5

Mechanism and action of griseofulvin

Answer 5

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

Question 6

What route of absorption is ideal for griseofulvin?

Answer 6

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

Question 7

Distribution of griseofulvin

Answer 7

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

Question 8

Adverse effects of griseofulvin
Cats & horses

Answer 8

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

Question 9

Amphotericin B

Answer 9

Polyene antifungal, reserved for severe illness

Question 10

Mechanism of Amphotericin B

Answer 10

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

Question 11

Common adverse effects in Amphotericin B

Answer 11

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

Question 12

Less common adverse effects of Amphotericin b

Answer 12

Fever
Thrombophlebitis
Nausea, vomiting, anorexia
Anemia

Question 13

How to decrease Amphotericin B toxicity

Answer 13

Fluid pretreatment
Slow IV infusion
Liposomal formulations

Question 14

Drug interactions with Amphotericin b
- flucytosine

Answer 14

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

Question 15

Drug interactions with Amphotericin b
- azole

Answer 15

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

Question 16

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

Answer 16

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

Question 17

Common ADRs of azole drugs

Answer 17

Hepatotoxicity, not safe during pregnancy

Question 18

Older azole drugs

Answer 18

Imidazoles
- ketoconazole: systemic

Question 19

Newer azole drugs

Answer 19

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

Question 20

Dimorphic fungi spectrum drugs

Answer 20

Blastomyces
Histoplasma
Cryptococcus
Sporothrix
(Most lipophilic will treat)

Question 21

Dermatophytes spectrum drugs

Answer 21

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

Question 22

PK of ketoconazole

Answer 22

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

Question 23

AE of ketoconazole

Answer 23

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

Question 24

Adverse effects mechanism of ketoconazole
Inhibits? Decreases?

Answer 24

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

Question 25

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

Answer 25

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

Question 26

Triazoles

Answer 26

Itraconazole, fluconazole, voriconazole

Question 27

Itra, flu & vori

Answer 27

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

Question 28

Itraconazole adverse effects

Answer 28

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

Question 29

PK of itraconazole

Answer 29

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

Question 30

Fluconazole mechanism

Answer 30

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

Question 31

Fluconazole adverse effects

Answer 31

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

Question 32

Fluconazole formulations

Answer 32

Tablets, suspension, injection

Question 33

Vorizconazole

Answer 33

More activity against fursarium Fungicidal against aspergillus

Question 34

Voriconazole absorption

Answer 34

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

Question 35

Possible toxicity of voriconazole in cats

Answer 35

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

Question 36

What drug is an allyamine antifungal?

Answer 36

Terbinafine Inhibits ergosterol synthesis by inhibiting squalene epoxidase Fungicidal

Question 37

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

Answer 37

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

Question 38

Absorption of Terbinafine

Answer 38

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

Question 39

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

Answer 39

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

Question 40

Antiviral drugs use

Answer 40

Limited, viral infections are self limiting Judicious use

Question 41

What kind of virus is used for nucleoside analogs?

Answer 41

Antihepetic drugs, prodrugs Better bioavailability

Question 42

Valacyclovir used for what virus?

Answer 42

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

Question 43

Types of inhibitors in anti-influenza drugs

Answer 43

Adamantane inhibitors Amantadine & rimantadine Neuraminidase inhibitors Oseltamsvir

Question 44

Which drug has more activity against fursarium?

Answer 44

Voriconazole

Question 45

What mycolic fungi does voriconazole have more activity against?

Answer 45

Fursarium

Question 46

Which fungi is voriconazole “cidal” against?

Answer 46

Aspergillus

Question 47

Which azole drug is more lipophilic than fluconazole?

Answer 47

Voriconazole

Question 48

Fluconazole varies from voriconazole how?

Answer 48

Voriconazole is more lipophilic than fluconazole

Question 49

What’s the relative protein binding of voriconazole?

Answer 49

Intermediate protein binding

Question 50

Which azole is more water soluble than itraconazole / ketoconazole?

Answer 50

Viroconazole

Question 51

Viroconazole is more ________ than which azole drugs?

Answer 51

Water soluble Itraconazole/ketoconazole

Question 52

Relative protein binding in itraconazole

Answer 52

High protein binding

Question 53

How long does itraconazole stay concentrated in patients?

Answer 53

2-4 weeks in tissues

Question 54

Which azole drug is hydrophilic?

Answer 54

Fluconazole

Question 55

Relative protein binding of fluconazole?

Answer 55

Low protein binding

Question 56

What antifungal drugs have “cidal” properties?

Answer 56

Amphotericin B Terabinafine Viroconazole (against aspergillus)

Question 57

Which antifungal drugs have “static” properties?

Answer 57

Azoles Griseofulvin

Question 58

Which azole has the least amount of ADE ?

Answer 58

Fluconazole

Question 59

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

Answer 59

Paraplegia of hind limbs Viroconazole

Question 60

Mydriasis is caused by what PK and from what drug?

Answer 60

Decreased PLR Viroconazole

Question 61

Inappetance presented as _______ is caused by what drug?

Answer 61

Presented as lethargy and weight loss Viroconazole

Question 62

Azotemia cause by _________ can lead to _______?

Answer 62

Viroconazole Cutaneous drug reaction, ataxia, paresis