Antimicrobials

CHAPTER 10-3CHAPTER 10-3

Dr. Dipa Brahmbhatt VMD MpHDr. Dipa Brahmbhatt VMD MpH

dbrahmbh@yahoo.comdbrahmbh@yahoo.com

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

Antifungal Agents

• Antifungals are chemicals used to treat diseases caused by fungi (moldmold or yeastyeast)• 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

Blastomycosis - Dog

Thoracic radiograph from a dog with blastomycosis, showing diffuse miliary to nodular interstitial infiltrate Thoracic radiograph from a dog with blastomycosis, showing diffuse miliary to nodular interstitial infiltrate

Ringworm

Microsporum canis

Categories of Antifungals

Polyene antifungal agentsImidazole antifungal agents

Antimetabolic antifungal agentsSuperficial antifungal agents

Polyene antifungalsPolyene antifungals– Work by binding to the fungal cell membrane– Examples:

• Nystatin (Panalog®)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/staticAmphotericin 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.)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

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

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

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

Superficial antifungals

– Work by disrupting fungal cell division: -static

– E.g. griseofulvin (replaced itraconazole)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

Antimetabolic antifungals– Work by interfering with

the metabolism of RNA and proteins

– An example is flucytosine (Ancoban)flucytosine (Ancoban)• usually used in

combination with other antifungals for Cryptococcus

• Well absorbed by the GI tract

• Main side effect = bone marrow abnormalities

Antifungal Agents

• Other antifungals– Lufenuron (milbemycin oxime)Lufenuron (milbemycin oxime) is used to treat ringworm

in cats

– Lyme sulfurLyme sulfur is used topically to treat ringworm

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®) Acyclovir (Zovirax®) interferes with the virus’s synthesis of DNA

• used to treat ocular feline herpes virus infections• Tablets, suspension, injectable

– Interferons 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

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