Antimicrobials

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Antimicrobials

• CHAPTER 10-3
• Dr. Dipa Brahmbhatt VMD MpH
• dbrahmbh_at_yahoo.com

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Objectives

• Mechanisms of action of antibiotics
• Adverse drug reactions and how to mitigate these
• Selection of antibiotics Ab resistance, drug
  absorption, distribution, location of bacteria
  and drug elimination
• Antifungal drugs Advantages, Disadvantages and
  side effects

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Antifungal Agents

• Antifungals are chemicals used to treat
• diseases caused by fungi (mold or yeast)
• Some fungal diseases are superficial
  (dermatophytosis) others are deep or systemic
  (blastomycosis, cryptococcosis, histoplasmosis,
  coccidioidomycosis, candidiasis, sporotrichosis,
  aspergillosis)
• Diagnosed by fungal media or serologic tests
• Fungal infections are difficult to treat, and it
  takes a long course of drug treatment to resolve
  these infections.
• Most have severe SE

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Blastomycosis - Dog
Thoracic radiograph from a dog with
blastomycosis, showing diffuse miliary to
nodular interstitial infiltrate
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Ringworm
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Microsporum canis
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Categories of Antifungals

• Polyene antifungal agents
• Imidazole antifungal agents
• Antimetabolic antifungal agents
• Superficial antifungal agents

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Polyene antifungals

• Work by binding to the fungal cell membrane
• Examples
• Nystatin (Panalog)
• frequently prescribed for proliferation of
  Candida albicans in
• the GI tract a common result of antitiotic
  therapy
• Topical, oral, or IV
• Amphotericin B (Fungizone) -cidal/static
• Damages fungi-ergosterol makes cell membrane
  permeable
• Binds to lipoproteins (cholesterol) liver,
  spleen, lung
• used IV for systemic mycoses (deep mycoses)
  rapid onset of action (hrs.)
• light sensitive, and is usually given through a
  filter system because it can precipitate out of
  solution
• SE extremely nephrotoxic (most dogs)
  vasoconstrictive gt anoxia gt cell damage, fever,
  anorexia and nausea
• Monitor urinalysis, BUN and Creatine
• Also found in creams, lotions,and ointments

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Imidazole antifungals - AZOLES

• MOA leakage of the fungal cell membrane
  (ergosterol)
• Safer than Amphotericin B and used for
  deep/systemic mycosis
• Onset of action (-cidal) 2-5 days
• Examples
• Ketoconazole Mostly PO (and topical)
• Itraconazole PO
• Fewer side effects than Ketoconazole and
• Miconazole
• Fluconazole (Diflucan) Mostly PO (and IV)
• Especially useful in treating CNS infections
• Miconazole (Monistat, Conofite)
• Parenteral and topical forms only
• Clotrimazole topical. Intranasal infusion
  aspergillosis

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Imidazole antifungals - AZOLES

• SE
• GI (more with ketoconazole), vomiting high
  doses (cats split dose for less SE)
• Ketoconazole hepatotoxicity (especially if
  impaired before) monitor but Alanine
  aminotransferase ALT will go up and if this is
  only change continue using drug
• Use with caution in breeding dogs reduce steroid
  production in dogs reduce testosterone,
  glucocorticoids

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Imidazole antifungals

• Voriconazole
• If resistant to other imidazoles Aspergillus,
  Candida, Cryptococcus Fusarium
• Like amphotericin B but fewer SE
• Orally, can penetrate CNS. Injectable (many SE)
• SE Hepatotoxic, renal toxicity and anemia

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Superficial antifungals

• Work by disrupting fungal cell division -static
• E.g. griseofulvin (replaced itraconazole), an
  oral medication used to treat dermatophyte
  infections Trichophyton mentagrophytes,
  Microsprum canis/gypseum
• Administer with a fatty meal
• Oral powder (horses) and tablets. Ultramicrosize
  better absorbed than microsize formulation
• Dose for cat (conjugation prob) is LOWER than
  dogs
• SE Gastrointestinal (anorexia, v/d) and
  teratogenic side effects in cats cleft palate,
  skeletal/ skull/ nervous system deficits. Anemia
  and leukopenia are rare.
• Do not administer to pregnant, kittens or
  breeding animals

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Antimetabolic antifungals

• Work by interfering with the metabolism of RNA
  and proteins
• An example is flucytosine (Ancoban)
• usually used in combination with other
  antifungals for Cryptococcus
• Well absorbed by the GI tract
• Main side effect bone marrow abnormalities

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Antifungal Agents

• Other antifungals
• Lufenuron (milbemycin oxime) is used to treat
  ringworm in cats
• Lyme sulfur is used topically to treat ringworm

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Antiviral Agents

• Viruses are intracellular invaders that alter the
  host cells metabolic pathways
• Antiviral drugs act by preventing viral
  penetration of the host cell or by inhibiting the
  viruss production of RNA or DNA
• Antiviral drugs used in veterinary practice are
• Acyclovir (Zovirax) interferes with the viruss
  synthesis of DNA
• used to treat ocular feline herpes virus
  infections
• Tablets, suspension, injectable
• Interferons protect host cells from a number of
  different viruses
• Roferon-A - an interferon inducer
• used to treat ocular feline herpes virus
  infection and FeLV
• Stimulates noninfected cells to produce antiviral
  proteins

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References

• Romich, J.A. Pharmacology for Veterinary
  Technicians, 2nd edition. 2010.
• Bill, R.L. Clinical Pharmacology and Therapeutics
  for the Veterinary Technician, 3rd edition. 2006.
• http//ahdc.vet.cornell.edu/clinpath/modules/ua-ro
  ut/castssed.htm