midterm 3

• Mycology


  The study of fungi
• Schonlein & Gruby studied Trichophyton schoenleinii

  1839
• Langenbeck reported the yeastlike microorganism responsible for oral thrush (Candida albicans)


  Unknown
• Groups of Fungal Infections

  • Superficial mycoses
  • Deep-seated mycoses
• Superficial mycoses


  Most common, caused by dermatophytes, includes tinea or ringworm infections and Candida infections

  
• Ringworm Infections


  • Tinea capitis
  • Tinea barbae
  • Tinea faceie
  • Tinea cruris
  • Tinea pedis
  • Tinea manum
  • Tinea ungium (Onchomycosis)
  • Pityriasis versicolor
• Systemic Mycoses


  • Histoplasmosis
  • Sporotrichosis
  • Blastomycosis
  • Coccidioidomycosis
  • Cryptococcosis
  • Paracoccidioidomycosis
• Opportunistic Fungal Infections


  • Systemic candidiasis
  • Aspergillosis
  • Mucormycosis
  • Pneumocystis carinii
• Cutaneous Infections (Dermatophytoses)


  • Microsporum
  • Trichophyton
  • Epidermophyton
  • Malassezia furfur
• Subcutaneous Fungal Infections


  A group of fungal diseases in which both the skin and subcutaneous tissue are involved but typically no dissemination to the internal organ occurs
• Dermatophytoses


  Tinea or ringworm
• Sebum


  Acidic, fatty substance in and on the skin; functions as a natural antifungal agent and part of the innate immune system
• Propionic Acid


  An antifungal agent that is nonirritating and nontoxic
• Zinc Propionate


  Unstable to moisture, forming zinc hydroxide and propionic acid; used as fungicide, particularly on adhesive tape
• Sodium Caprylate


  Used topically to treat superficial dermatomycoses caused by C. albicans and Trichophyton, Epidermophyton and Microsporum spp.; from caprylic acid found in coconut or palm oil
• Undecylenic Acid


  10-Undecenoic acid, obtained from the destructive distillation of castor oil, can be used in concentrations up to 10%, traditionally used for athlete's foot
• Triacetin


  Its activity is due to acetic acid released by hydrolysis of the compound by esterases present in the skin
• Salicylic Acid


  Has both antiseptic and keratolytic properties, a poor antifungal agent
• Whitfield's Ointment


  Contains 6% benzoic acid and 6% salicylic acid in a petrolatum base; benzoic acid cannot penetrate the outer layer of the skin in infected areas thus used with keratolytic agents
• Haloprogin


  Used as a 1% cream for the treatment of superficial tinea infections; lesion typically worsens before it improves, inflammation and painful irritation are common
• Clioquinol


  3% ointment or cream is used as a treatment for Trichomonas vaginalis vaginitis; Vioform HC®: combination with hydrocortisone
• Ciclopirox Olamine


  An agent of choice for cutaneous candidiasis, tinea corporis, tinea cruris, tinea pedis and tinea versicolor; second-line treatment for onychomycosis; MOA: at low concentrations, it blocks transport of amino acids into the cells; at high concentrations, membrane integrity is lost and cellular contents leak out
• Flucytosine


  Ancobon®, used only in combination with Amphotericin B for the treatment of systemic mycoses and meningitis caused by Cryptococcus neoformans and Candida (synergistic); MOA: release 5-FU
• Polyenes


  • Amphotericin B
  • Nystatin
  • Natamycin
• Amphotericin B


  Fungizone®, naturally occuring, produced by Streptomyces nodosus; MOA: binds to ERGOSTEROL present in the cell membrane disrupting membrane function, allowing electrolytes to leak out from the cell, resulting in cell death; drug choice for systemic mycoses; S/E: renal toxicity, acute febrile reaction, anemia, phlebitis
• Nystatin


  Mycostatin®, first isolated from a strain of Streptomyces noursei; used for the treatment of Candida (monilial) infections; administered as an oral agent for the treatment of oral candidiasis; not absorbed systemically when administered orally
• Natamycin


  Natacyn®, obtained from Streptomyces natalensis; fungicidal and fungistatic at the same concentration range; supplied as 5% ophthalmic suspension intended for the treatment of fungal conjunctivitis, blepharitis, and keratitis
• Griseofulvin


  Grifulvin®, Grisactin®, Gris-PEG®, obtained from the mold Penicillium griseofulvum; MOA: interacts with the microtubules within the fungus to disrupt the mitotic spindle and inhibit mitosis (arrests cell division in metaphase); absorption is increased by FATTY FOODS; compliance with the drug regimen is mandatory
• Mechanism of Action of Allylamines and Related Compounds


  Inhibits squalene epoxidase resulting to shutting down of biosynthesis of ergosterol and cause an accumulation of squalene, which destablizes the fungal cell membrane
• Naftifine


  Naftin®, supplied in a 1% concentration in a cream and in a gel for the topical treatment of ringworm, athlete's foot and jock itch
• Terbinafine


  Lamisil®, available in 1% cream for topical administration for the treatment of tinea pedis, tinea corporis, and tinea cruris
• Tolnaftate


  Tinactin®, Aftate®, NP-27®, not an allylamine but has MOA the same with allylamine compounds; formulated into preparations intended to be used with artificial fingernails to counteract the increased chance of ringworm of the nail beds
• Antifungal Spectrum of Azole Antifungal Agents

  Effective against most fungi that cause superficial infections of the skin and mucous membrane; also exhibit activity against yeasts that cause systemic infections
• Mechanism of Action of Azole Antifungal Agents

  Interacts with C-14-demethylase to block demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes. This inhibition disrupts membrane function and increases permeability
• Structure-Activity Relationships of Azole Antifungal Agents

  The basic structural requirement for members of the azole class is a weakly basic imidazole or 1,2,4-triazole ring; the most potent antifungal azoles possess two or three aromatic rings
• Clotrimazole


  Lotrimin®, Mycelex®, a broad-spectrum antifungal drug that is used topically for the treatment of tinea infections and candidiasis; 1% vaginal cream and tablets of 100 mg and 500 mg for vulvovaginal candidiasis; extremely stable, with a shelf-life of more than 5 years
• Econazole


  Spectazole®, 1% cream for the topical treatment of local tinea infections and cutaneous candidiasis
• Butoconazole


  Femstat®, supplied as vaginal cream intended for vaginal candidiasis
• Sulconazole


  Exelderm®, supplied in 1% concentration for the treatment of local tinea infections, such as jock itch, athlete's foot, and ringworm
• Oxiconazole


  Oxistat®, used in cream and lotion dosage forms in 1% concentration for the treatment of tinea infections