Antifungal agents

Cellular targets of antifungal drugs.

• Amphotericin B

• Mechanism of action:
• Binds to ergosterol of fungal cell
membranes to form pores or channels,
which result in leakage of cell contents.

• Fungicidal: against most organisms

causing systemic mycoses, including
Aspergillus, Blastomyces, Cryptococcus,
and Histoplasma spp.

• Therapeutic uses:
• treat systemic fungal infections in dogs,
cats, horses, and birds.
• To reduce toxicity it is combined with
ketoconazole, fluconazole
• Pharmacokinetics:
• After IV administration, it slowly distributes to most tissues except
the CNS, eye, and bone.
• Adverse effects:Renal toxicity (causes renal vasoconstriction and
decreased GFR
Nystatin and Natamycin
•Chemistry: derived from Streptomyces spp.

•Mechanism of action:
• act by binding to erogsterol of fungi membrane to alter
permeability and allow leakage of cell contents.
• Fungicidal to yeast infections caused by Candida spp

•Therapeutic uses:
• Topically to treat infections of the eye, ear, and skin
• Orally to treat mucosal yeast infections of mouth and GI
• Feed additive in poultry to prevent crop mycosis

•Pharmacokinetics: not absorbed orally and is excreted in feces.

•Administration: orally and topical

•Adverse effects: rare

• Azoles:
• Systemic use: Ketoconazole, itraconazole and fluconazole
• Tropical use: miconazole and clotrimazole

• Mechanism of action:
• Inhibit synthesis of ergosterol in fungal cytoplasm by inhibiting
P450 dependent enzymes (more specific 14 alpha demethylase)
and increasing cellular permeability.

• Inhibits mammalian steroid synthesis at high doses.

• Therapeutic uses:
• Ketoconazole, Fluconazole and itraconazole are used in dogs,
cats, horses, and birds for systemic mycoses

• In dogs and cats used for the treatment of

hyperadrenocorticism

• Clotrimazole and miconazole are used topically in the treatment

of Candida, Aspergillus, and dermatophyte infections.
• Pharmacokinetics:
• well absorbed after oral administration
• Distributed in tissues high in lipid content and used to treat
meningitis
• Metabolized by liver and excreted in bile.

• Administration:
• Ketoconazole: orally for 3–6 months for systemic mycotic
infections.
• Fluconazole and itraconazole: orally or IV to dogs and cats for
systemic mycoses for periods of 1–3 months
• Clotrimazole and miconazole: applied topically for the treatment
of yeast or dermatophyte infections or via nasal infusion for
treating nasal aspergillosis.

• Adverse effects:
• Anorexia, vomiting, and diarrhea may occur, especially in cats,
treated with ketoconazole.
• Suppress adrenal or gonadal steroids but the effects are
transient at doses employed in antifungal therapy.
• Terbinafine

• Mechanism of action:
• inhibits the synthesis of ergosterol
• Unlike azoles, terbinafine does not block cytochrome P450
enzymes.
• It inhibits squalene epoxidase which prevent conversion of
squalene to ergosterol

• fungicidal against dermatophytes and fungistatic against

yeast

• Therapeutic uses:
• Orally or topically to treat dermatophytic infections in dogs
and cats.

• treat birds for systemic mycotic infections such as

Aspergillosis.

• Adverse effects: Well tolerated by animal

Griseofulvin

•Mechanism of action:
• binds to microtubules to inhibit spindle formation and
mitosis
• It is fungistatic for Microsporum spp. and Trichophyton spp.
• Its action is slow as infected cells are shed and replaced with
uninfected cells.

•Therapeutic uses:
• used in dogs, cats, and horses for dermatophyte infections.

•Pharmacokinetics:
• It distributes to keratin precursor cells of skin, hair and nails.
• It is metabolized by the liver

•Administered orally twice a day to dogs and cats and once daily to
horses for 4–6 weeks.

•Adverse effects: rare

• Flucytosine

• Mechanism of action

Flucytosine is metabolized to 5-
fluorouracil within fungal
organisms. The 5-fluorouracil
competes with uracil and is
incorporated into fungal RNA and
inhibits synthesis of both DNA
and RNA which results in death of
the fungal organism.

5-fluorodeoxyuridine
It is fungicidal against Cryptococcus, monophosphate
Candida, and Aspergillus deoxythymidine
monophosphate.
• Therapeutic uses:
• Flucytosine is combined with amphotericin B for synergistic
action in the treatment of Cryptococcal infection in dogs and
cats.

• amphotericin B increase fungal uptake of flucytosine

• used alone in treating aspergillosis and candidiasis

• Pharmacokinetics:
• well absorbed orally and widely distributed to CNS.
• It is excreted unchanged in urine.

• Administration: orally 3–4 times a day for a minimum of 4 weeks.

• Adverse effects:
• causes reversible neutropenia, thrombocytopenia and bone
marrow depression.

• Caution must be exercised in patients undergoing radiation or

chemotherapy with drugs that depress bone marrow.
 Antiviral Drugs

OVERVIEW

• few drugs are selective enough to prevent viral replication

without injury to the infected host cells.

• Viruses are obligate intracellular parasites

• they use the host’s metabolic machinery

 Mechanism of antiviral actins

1.Inhibits uncoating
amantadine

2.Inhibits transcription
acyclovir, zidovudine

3.Inhibits translation
idoxuridine

4.Inhibits shedding
oseltamivir
Amantadine

Mechanism of action:
•interfere with the function of the viral M2 protein and block
uncoating of the virus particle and preventing viral release and
subsequent replication within infected cells

•Amantadine antagonizes the N-methyl-D-aspartate (NMDA)

receptor in the CNS. NMDA receptors which is important in pain
sensation, especially chronic pain.

•Amantadine combined with other analgesics such as opiates or

NSAIDs to alleviates chronic pain.

Therapeutic uses:
•adjunct to NSAIDs to treat chronic pain in dogs and cats.
•To treat some, but not all, influenza viruses.
Acyclovir
Mechanism of action:
•Acyclovir is metabolized to the monophosphate
by thymidine kinase, which is more active in the
virus than in the host cell.

•host cell then converts the monophosphate to

the triphosphate. When incorporated in the
growing strand, it prevents the viral DNA
polymerase from adding dGTP and ends
nucleotide chain prematurely.

Therapeutic uses:
•used to treat ocular and respiratory infections
of herpes virus of cats.

Pharmacokinetics:
•widely distributed in body tissues and fluids,
including the brain, semen, and CSF
Adverse effects: Incorporation
•Leucopenia and anemia may occur. These areof Acyclo-GTP
leads to chain
reversible if therapy is discontinued. termination
Zidovudine (AZT)
•Zidovudine is an analog of thymidine.

•Mechanism of action:
• Zidovudine is phosphorylated by host cell to 5-triphosphate,
which competes with host 5-thymidine
• Thymidine is essential for viral DNA formation by reverse
transcriptase
• Incorporation of the 5-triphosphate zidovudine into the viral
DNA chain produces the termination of viral DNA synthesis.
• Mammalian α-DNA polymerase does not incorporate the
zidovudine.

•Therapeutic uses:
• treat feline immunodeficiency virus (FIV) where it produces
temporary alleviation of the clinical signs and survival

•Adverse effects:
• Anemia and reduction in hemoglobin are common side
effects
Idoxuridine:
• A false RNA analog resembles Uridine

• Mechanism of Action:
• When incorporated into the viral transcript, it prevents the
translation of transcripts

• Therapeutic uses:
• Used topically to treat Herpes keratitis in cat

Oseltamivir phosphate (Tamiflu)

• Mechanism of action:
• Inhibits neuraminidase which reduces the shedding of
influenza virus particles

• Therapeutic uses
• Control influenza viruses
• Treatment and prophylaxis of H5N1 influenza (bird flu)
• Treat canine parvoviruses
• Attenuate secondary bacterial pneumonia