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Antimicrobials

Antimicrobials. CHAPTER 10-3 Dr. Dipa Brahmbhatt VMD MpH dbrahmbh@yahoo.com. Objectives. Mechanisms of action of antibiotics Adverse drug reactions and how to mitigate these

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Antimicrobials

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  1. Antimicrobials CHAPTER 10-3 Dr. DipaBrahmbhatt VMD MpH dbrahmbh@yahoo.com

  2. 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

  3. 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

  4. Blastomycosis - Dog Thoracic radiograph from a dog with blastomycosis, showing diffuse miliary to nodular interstitial infiltrate

  5. Ringworm

  6. Microsporum canis

  7. Categories of Antifungals Polyene antifungal agents Imidazole antifungal agents Antimetabolic antifungal agents Superficial antifungal agents

  8. Polyeneantifungals • Work by binding to the fungal cell membrane • Examples: • Nystatin (Panalog®) • frequently prescribed for proliferation of Candida albicansin the GI tract; a common result of antitiotic therapy • Topical, oral, or IV • Amphotericin B (Fungizone®): -cidal/static • Damages fungi-ergosterolmakes 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> anoxia > cell damage, fever, anorexia and nausea • Monitor: urinalysis, BUN and Creatine • Also found in creams, lotions,and ointments

  9. 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

  10. 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

  11. 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

  12. Superficial antifungals • Work by disrupting fungal cell division: -static • E.g. griseofulvin (replaced itraconazole), an oral medication used to treat dermatophyteinfections: Trichophytonmentagrophytes, Microsprumcanis/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

  13. 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

  14. Antifungal Agents • Other antifungals • Lufenuron (milbemycinoxime)is used to treat ringworm in cats • Lyme sulfur is used topically to treat ringworm

  15. Antiviral Agents • Viruses are intracellular invaders that alter the host cell’s metabolic pathways • Antiviral drugs act by preventing viral penetration of the host cell or by inhibiting the virus’s production of RNA or DNA • Antiviral drugs used in veterinary practice are: • Acyclovir (Zovirax®) interferes with the virus’s 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

  16. 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-rout/castssed.htm

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