Antifungals Flashcards
What are some examples of local fungal infections?
Dermatophytosis (Ringworm) due to Trichophyton, Microsporum, and Epidermophyton.
Candida (yeast, Moilia)
What are some examples of systemic mycoses?
Histoplasmosis, Aspergillosis, Coccidiomycosis, Blastomycosis, Crytococcus, Sporotrichosis, etc.
What are examples of polyene antifungals?
Amphotericin B, Nystatin, and Natamycin.
What are some examples of azole anti fungal drugs?
Ketoconazole, Clotrimazole, Miconazole, Enilconazole, and Thiabendazole.
Which anti fungal drugs are broad-spectrum?
- Ciclopirox olamine
- Cuprimyxin
- Haloprogin
- Polyenes
- Azoles
- Terbinafine
What is the most common narrow-spectrum anti fungal and what does it treat?
Tolnaftate. It treats Malassezia canis.
What are some topical anti fungal drugs?
- Iodides
- Organic acids (Salicylic acid, Benzoic acid, fatty acids, etc.)
- Lime sulfur
- Thymol
- Hexachlorphene
What are some systemic anti fungal drugs? (6)
- Griseofulvin
- Amphotericin B
- Flucytosine
- Azoles (Ketoconazole)
- Allylamines (Terbinafine)
- Lufenuron
Which three systemic anti fungal drugs are most commonly used?
- Griseofulvin
- Amphotericin B
- Ketoconazole
What are polyenes?
Polyenes are broad spectrum topical anti fungal drugs.
Name three polyenes.
- Nystatin
- Amphotericin B
- Natamycin
What is the MOA of polyenes?
Fungicidal due to rapid alteration of fungal cell membrane permeability by binding irreversibly to ergosterol.
What are azoles?
Broad spectrum topical and systemic anti fungal drugs.
Which azoles are administered topically? (4)
- Clotrimazole
- Miconazole
- Enilconazole
- Thiabendazole
Which azole is administered both topically and systemically?
Ketoconazole
Which azoles are administered systemically? (2)
- Itraconazole
2. Fluconazole
What is the MOA of azoles?
Fungistatic due to alteration of fungal cell permeability by blocking conversion of lanosterol to ergosterol, which is catalyzed by 14-a demethylase.
What are allylamines?
Systemic antifungals
What is the most commonly used allylamine?
Terbinafine
What is the MOA of Allylamines?
Fungicidal due to inhibition of ergosterol synthesis by inhibiting squalene-epoxidase that converts squalene to squalene-epoxide resulting in accumulation of squalene.
What is Griseofulvin, how is it administered, and what does it treat?
Griseofulvin is a systemic anti fungal that is given orally for treatment of dermatophytes because of selective deposition in new keratin.
What is the MOA of Griseofulvin?
Fungistatic due to interference with microtubule function and inhibiting mitosis.
How is Griseofulvin absorbed?
GI absorption is low and is enhanced by decreasing particle size and a high fat meal.
How long does Griseofulvin have to be given to provide a successful treatment?
Treatment takes 3-6 weeks in small animals.
T/F: Griseofulvin is a hepatic enzyme inducer.
True
What are some adverse effects of Griseofulvin?
Causes GI irritation and cats are sensitive to its toxicity (idiosyncratic reactions.)
What toxic effects does Griseofulvin have in cats?
It is teratogenic, hepatotoxic, and causes idiosyncratic bone marrow suppression (neutropenia, anemia, and pancytopenia.)
What is Amphotericin B?
Part of the polyene class of antifungals and can be topical or systemic.
How is Amphotericin B administered?
Given IV because it has poor oral absorption. It has a wide distribution, except to the CNS.
What does Amphotericin B treat?
- Most effective drug for treatment of systemic mycoses in immunocompromised animals.
- Combined with Flucytosine for cryptococcal meningitis in cats or with azoles for treatment of systemic mycoses.
- Used topically for Candida
What is Amphotericin B not effective against?
Aspergillus
What are some toxic effects of Amphotericin B?
- Nephrotoxicity (narrow safety margin.)
- Hypokalemia
- Hypotension
- Cardiac arrhythmias
Liposoma encapsulated preparation is less toxic than colloidal suspension preparation.
What kind of drug is Flucytosine?
Systemic antifungal
What is the MOA for Flucytosine?
Fungicidal due to inhibition of nucleic acid synthesis by inhibiting thymidylate synthase.
How is Flucytosine administered and how is it distributed in the body?
Readily absorbed orally and has a wide distribution, including the CNS.
What are three adverse effects of Flucytosine?
- GI irritation
- Bone marrow suppression
- Liver dysfunction
How is Ketoconazole administered?
It is given orally for broad-spectrum activity. Requires acidic pH for dissolution and oral absorption.
T/F: Ketoconazole has good penetration in the CNS.
False. Ketoconazole has poor penetration in the CNS.
How long does it take for Ketoconazole to work?
It has a slow effect. It takes 3-6mo to take effect.
What is Ketoconazole not very effective against?
Aspergillosis
What are the adverse effects of Ketoconazole?
- Inhibits cortisol and testosterone synthesis in small animals.
- Inappetence
- Pruritus and alopecia in dogs
- Should not be give to pregnant animals (teratogenic!)
Who is more sensitive to Ketoconazole, dogs or cats?
Cats are more sensitive than dogs to toxicity, but large doses cause hepatotoxicity in cats and dogs.
How is Itraconazole similar to Ketoconazole?
They have similar pharmacokinetics and therapeutic uses. They are both contraindicated during pregnancy.
What is are three differences between Itraconazole and Ketoconazole?
Itraconazole’s oral absorption does not depend on acidity, it is effective against Aspergillus, and it does not inhibit cortisol or testosterone synthesis at therapeutic doses.
What is the preferred drug for treating systemic Blastomycosis and Histoplasmosis?
Itraconazole
What is the drug of choice for treating Sporotrichosis?
Itraconazole
What is Fluconazole effective at treating?
Acute cryptococcal meningitis
How is Fluconazole administered?
IV
What are the differences between Fluconazole and Ketoconazole?
Fluconazole’s oral absorption does not depend on acidity and it has more penetration to tissues than Ketoconazole (and Itraconazole) and crosses the CNS at therapeutic levels.
How serious are the side effects of Fluconazole?
Minimal
What kind of drug is Terbinafine?
Broad-spectrum topical antifungal.
What is Terbinafine used to treat and how is it administered?
Terbinafine is a safe and effective drug against dermatohytosis. It is available as tablets and topical cream.
What is one side effect of Terbinafine?
May elevate ALT in cats
What is the MOA of Lufenuron?
Inhibits cell wall synthesis due to inhibiting chitin synthesis by inhibiting chitin synthetase.
What kind of drug is Lufenuron?
Systemic antifungal
How is Lufenuron administered in cats and dogs?
Dogs: Orally
Cats: Injection
T/F: Large doses are safe and effective in treating dermatophytosis in dogs and cats.
True
What drug is used to treat keratitis in horses?
Clotrimazole
What two drugs are used to treat canine nasal aspergillosis?
Clotrimazole and Enilconazole
What drug is used to treat systemic aspergillosis?
Itraconazole PO for 2-3 months
