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MYCV 311
LECTURE / SECOND SEMESTER
Mr. Joseph Casinsinan

WEEK 3: MYCOTOXICOSIS

PRESENTING SYMPTOMS AND SEVERITY DEPEND ON:  Inhalation of spore-borne toxins also constitutes an important form of
exposure.
 Supportive therapy, there are almost no treatments for mycotoxin exposure.
1. Type of mycotoxin;  Not communicable from person to person.

2. Amount and duration of exposure;

3. Route of exposure;

4. Age, sex and health of the exposed individual.

5. Other circumstances, such as malnutrition, alcohol abuse, infectious disease status, and
other toxin exposures may act synergistically to compound

INTRODUCTION

 More than 100 toxigenic fungi and more than 300 compounds now
recognized as mycotoxins
 Number of people affected is unknown
 Majority result from eating contaminated foods.
 Some mycotoxins are dermonecrotic, and cutaneous or mucosal contact
with mold-infected substrates may result in disease

MYCETISM

❑ Or MYCETISMUS

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❑Fungus which is eaten causes toxic effects ❑Two of these are yellow rice toxicosis in Japan and alimentary toxic aleukia in the
former Soviet Union.
❑Mushroom poisoning
❑There are also other fungi responsible for mycotoxicosis.
❑May cause gastrointestinal disease, dermatitis or death.

AMANITA PHALLOIDES
accounts for the majority of fatal
mushroom poisonings worldwide.

MYCOTOXICOSIS

❑Result from ingestion of food or feed that contains MYCOTOXINS.

❑Variety of mycotoxins are produced by mushrooms (e.g. Amanita species), and their
ingestion results in a dose-related disease called mycetismus.

AFLATOXIN PSYCHOTROPIC AGENTS

❑MOST POTENT, which is peptide ❑ Toxic metabolites produced by fungi have

elaborated by produced primarily by been used by primitive tribes for religious,
ASPERGILLUS FLAVUS and magical and social purposes.
ASPERGILLUS PARASITICUS- other
species of aspergillus produce aflatoxins as well ❑The hallucinogenic agents (dlysergic acid,
psilocybin) are produced by the
❑Is a frequent contaminant of peanuts, corn, PSILOCYBE species and other fungi.
grains and other foods.
❑In the 20th century, problems involving
❑Acute aflatoxicosis has been manifested in toxins of fungi were seen with the
humans as an acute hepatitis. recreational use of psychotropic agents such
as psilocybin and psilocin, as well as the
semisynthetic derivative lysergic acid
❑Highly toxic to animals and birds, and diethylamide (LSD).
probably to human beings as well cause HEPATOMAS in ducklings and rats, and its
possible carcinogenic effect in human beings has caused great concern.

❑AFLATOXIN B1 is the most potent natural carcinogen known and is the major
aflatoxin produced by toxigenic strains

ERGOT ALKALOIDS

❑ ERGOTOXICOSIS (ergotism) - toxic

alkaloids produced by the fungus CLAVICEPS
PURPUREA - growing on the fruiting heads of
rye.

❑LYSERGIC ACID - structure common to all

ergot alkaloids

▪ Hallucinogen Lysergic Acid Diethylamide

(LSD) was discovered as a result of research with
these compounds. KEY POINTS

❑Hardened masses of fungal tissue (SCLEROTIA) that are formed when the fungus ❑ Mycotic poisoning is of two types:
invades the floret and replaces the grain of wheat, barley, or rye.
1. Mycetism
OTHER MYCOTOXICOSES 2. Mycotoxicosis

❑ Classic examples of human diseases caused by Fusarium mycotoxins include
ALIMENTARY TOXIC ALEUKIA, UROV or Kashin–Beck disease and
AKAKABIBYE (scabby grain intoxication).
❑AFLATOXIN is elaborated by Aspergillus flavus and related molds
❑ERGOT ALKALOIDS: Ergotoxicosis (ergotism) is due to the toxic alkaloids
produced by the fungus Claviceps purpurea

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❑ Psychotropic agents: Toxic metabolites produced by fungi such as psilocybin and
psilocin, as well as the semisynthetic derivative lysergic acid diethylamide (LSD)

WEEK 3: ANTIFUNGAL DRUGS

AMPHOTERICIN B (AMB)

❑administered intravenously (IV) for

serious fungal infections and has been
the drug of choice for most life-
threatening fungal infections.

A. POLYENE ANTIFUNGALS ❑Resistance is infrequent, - there is

some reduced AMB sensitivity among
some Candida species.

▪ Resistance is associated with lower

membrane levels of ergosterol.

❑Liposomal AMB formulations are

available that have reduced toxicity.

❑used in combinations with 5-

fluorocytosine or fluconazole but only
with very specific fungi in specific body
locales.

GENERAL CHARACTERISTICS
❑Polyenes bind to ergosterol in fungal membranes - creating ion channels -leading to
leakage and cell death.
❑Polyene membrane damage through an oxidative stress - rapid killing.
❑AMB also stimulates the fungus to produce oxygen radicals, and to modulate
macrophage activity by stimulating production of pro-inflammatory cytokines, reactive
oxygen intermediates and nitric oxide
❑the small size of these liposomes (<100 nm) results in prolonged circulation allowing
distribution into many different organs

❑Polyenes also bind to cholesterol (but less avidly than ergosterol - are quite toxic. ❑ensures that AMB remains associated with the liposome bilayer until it comes into
contact with a fungus, minimizing the adverse effects of AMB on host tissues

 Toxicity is reduced by the use of liposomal formulations.

❑Have POOR gastrointestinal absorption. NYSTATIN

❑NOT ABSORBED from the

gastrointestinal tract

❑used topically, intravaginally,

or orally to treat Candida
overgrowth or infections of
cutaneous or mucosal surfaces.

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B. 5-Fluorocytosine (5-FC, flucytosine)

5-FC

❑an antimetabolite converted in fungal cells to 5-fluorouradylic acid - competes with

uracil to cause miscoding and disruption of RNA, protein, and DNA synthesis.

❑resistance develops quickly if used alone - 5-FC is used in combination with

amphotericin B or fluconazole for specific infections.

AZOLE DRUGS

❑Triazole agents - have a broad spectrum of activity.

❑The most commonly used azoles, include fluconazole, itraconazole, econazole,

terconazole, butoconazole, and tioconazole.

❑Newer triazoles (ie, voriconazole, posaconazole, ravuconazole) are active against

fluconazole-resistant strains of Candida.

FLUCONAZOLE
C. IMIDAZOLE DRUGS

❑azole drugs with three nitrogen in the azole ring.

❑better systemic activity than the Imidazoles.

1. Fluconazole

a) excellent oral bioavailability.

b) used for systemic infections - most commonly with Candida and
Coccidioides - Coccidioidal meningitis in acquired immunodeficiency
syndrome (AIDS), and as maintenance therapy after cryptococcal
meningitis.
c) used in combination with other drugs in specific situations for specific fungi.

ITRACONAZOLE

❑Lipophilic imidazole drug - administered orally.

IMIDAZOLE
❑Treatment of mucocutaneous candida infections, non–lifethreatening aspergillus
infections, moderate or severe histoplasmosis or blastomycosis, and sporotrichosis.
❑azole drugs with two nitrogen in the azole
ring - commonly used for localized surface
VORICONAZOLE
infection

❑Inhibit the lanosterol 14-a-demethylase ❑Has a broad spectrum of activity - exception of the non-septate fungi (Zygomycetes)
interfering with ergosterol synthesis.
❑may be effective against other fungi that have developed AMB resistance.
1. KETOCONAZOLE - orally
administered but is used only in non–life
❑Now a primary drug for treatment of invasive aspergillosis as an alternative to AMB
threatening fungal infections.

POSACONAZOLE
2. MICONAZOLE - used topically against
dermatophytes and candida spp.
❑a newer azole licensed for treatment of Zygomycetes (nonseptate fungi) infections.

ECHINOCANDINS
D. TRIAZOLES
❑Inhibit fungal glucan synthesis - leading to a weakened cell wall and cell lysis.

1. Include caspofungin, micafungin, and anidulafungin.

2. Effective against Aspergillus spp., Candida spp.,

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Pneumocystis jiroveci, and a variety of other fungi.

TOPICAL ANTIFUNGAL

❑including Imidazoles, Allylamines - terbinafine and naftifine, tolnaftate, and many

others

❑may be used for dermatophytes and mucosal yeast infections.

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