ANTIFUNGAL CHEMOTHERAPY

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ANTIFUNGAL CHEMOTHERAPY

• Géza T. Terézhalmy, D.D.S., M.A.
• Endowed Professor in Clinical
• Dentistry
• The UTHSCSA Dental School
• San Antonio, Texas
• Terezhalmy_at_uthscsa.edu

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Antifungal Chemotherapy

• Fungi
• Free-living, eukaryotic organisms that exist as
  yeasts or molds
• Over 100,000 species
• Only a few pathogenic in humans
• Saprophytic members of the soil microbial flora
• The lungs are the most common portal of entry of
  pathogenic fungal organisms
• Immunocompromised patients
• Commensal organisms
• Typically on oral, vaginal, or GI mucosa
• Less often of the skin and respiratory epithelium

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Antifungal Chemotherapy
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Antifungal Chemotherapy

• Pharmacological strategies
• Only a small number of unique targets for
  antifungal chemotherapy
• Chief reason
• Fungal and human cells, because of their
  phylogenetic similarity are both eukaryotic
• Homologous metabolic pathways for protein
  synthesis and cell division
• Sterols are essential structural and functional
  components of all plasma membranes
• Cholesterol is the predominant sterol in human
  cells
• Ergosterol, which is structurally similar to
  cholesterol, presents a unique target in fungi

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Antifungal Chemotherapy
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Antifungal Chemotherapy

• Pharmacodynamics
• Inhibitors of ergosterol synthesis
• Azoles
• Block a fungus-specific cytochrome P450 enzyme,
  14?-sterol demethylase, which catalyzes an
  essential step in ergosterol synthesis
• Leading to structural and functional damage and
  cell death
• Not entirely selective, they also inhibit hepatic
  cytochrome P450 enzymes
• Drug-drug interactions
• Major adverse effect is hepatotoxicity

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Antifungal Chemotherapy
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Antifungal Chemotherapy
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Antifungal Chemotherapy

• Pharmacodynamics
• Ergosterol binding drugs
• Polyenes
• Bind to ergosterol in fungal plasma membrane
• Through a pore-forming mechanism increase
  membrane permeability, which leads to leakage of
  essential cellular components and cell death
• Severe systemic toxicity is a limiting factor in
  their clinical use

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Antifungal Chemotherapy
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Antifungal Chemotherapy

• Pharmacodynamics
• Inhibitors of DNA synthesis
• Flucytosine
• Converted to 5-fluorouracil
• Inhibits thymidylate syntase,
• Bone marrow suppression and hepatic toxicity

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Antifungal Chemotherapy

• Pharmacotherapeutics
• Inhibitors of microtubule function
• Griseofulvin
• Inhibits the formation of the mitotic spindle
• Accumulates in the keratinized layer of the skin

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Antifungal Chemotherapy

• Pharmaco-kinetics
• Absorption
• Route of administration
• Distribution
• Passive diffusion into foci of infection
• Metabolism
• Excretion

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Antifungal Chemotherapy

• Pharmacotherapeutics
• The medical management of most mycoses fall in
  the purview of physicians
• However, evidence of fungal infection may
  manifest in the HN area
• Extent to which these infections relate to the
  dental professions anatomic field of
  responsibility
• Extent to which a viral infection may mandate
  modification of dental therapy or alter prognosis
• Extent to which the presence of a viral infection
  may impact on care givers

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Antifungal Chemotherapy

• Pharmacotherapeutics
• Infections with Candida spp. represent the most
  common fungal infection affecting the HN area
• Oral health care providers have the primary
  responsibility to diagnose and treat fungal
  infections of the orolabial region
• Pseudomembraneous candidiasis
• Erythematous candidiasis
• Hyperplastic candidiasis
• Angular cheilitis

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Antifungal Chemotherapy

• Pharmaco-therapeutics
• Diagnosing orolabial candidiasis
• Clinical manifestations
• Cytology
• 20 KOH
• Fungal culture
• PCR
• Serology

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Antifungal Chemotherapy
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Antifungal Chemotherapy
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Antifungal Chemotherapy
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Antifungal Chemotherapy
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Antifungal Chemotherapy

• Pharmaco-therapeutics
• Primary line of antifungal chemotherapy
• RX
• Nystatin, 200,000 units/troches
• Disp. 70 troches
• Sig. Let 1 troche slowly dissolve in mouth 5
  times per day

• RX
• Nystatin, 100,000 units/mL
• Disp. 240 mL
• Sig. Rinse with 1 tsp for 2 minutes 5 times per
  day
• RX
• Clotrimazole, 10-mg troche
• Disp. 70 troches
• Sig. Let 1 troche slowly dissolve in mouth 5
  times per day

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Antifungal Chemotherapy

• Pharmaco-therapeutics
• Secondary line of antifungal chemotherapy
• RX
• Fluconazole, 100-mg tablet
• Disp. 15 tablets
• Sig.Take 2 tablets stat, PO, then 1 tablet once
  per day

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Antifungal Chemotherapy

• Pharmacotherapeutics
• Tertiary line of antifungal chemotherapy
• Itraconazole
• Voriconazole
• Amphotericin B
• Flucytosine

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Antifungal Chemotherapy