Toxic Fungi PDF

Toxic fungi  General Considerations Regarding Exposure To Biological Agents There are at least five important considerations for the clinician managing an exposure involving a biological substance: 1. identification of the poison 2. quantification of the dose 3. lack of spe...

Toxic fungi  General Considerations Regarding Exposure To Biological Agents There are at least five important considerations for the clinician managing an exposure involving a biological substance: 1. identification of the poison 2. quantification of the dose 3. lack of specific laboratory analysis 4. lack of specific antidotes 5. and use of nonmedical consultants 1-Identification of the Poison In many cases of poisoning or overdose, the identification of the offending medication or chemical can be determined with little difficulty by knowing the accurate patient or family history, over-the-counter and prescription bottles retrieved from the scene, ingredient listings on containers. When triaging exposures involving biological agents, however, the above methods of identification may be of little or no value due to: 1-Plants, mushrooms, spiders and snakes are not conveniently tagged with their unique botanical, mycological, or zoological nomenclature. 2-Marked variation exists inter- and intra-species, between geographic or structural location, and even seasonally. Accurate identification may hinge on a combination of piecing together a fragmented exposure history, recognizing a constellation of signs and symptoms, and/or utilizing the expertise of a non- healthcare professional such as a botanist or mycologist. The severity of the event is best judged by the nature and extent of the signs, symptoms, or laboratory abnormalities.  2-Quantification of a Dose It is unknown exactly how many milligrams of the toxic substance present in the ingested part of the toxic biological agent. Individual susceptibility may play a major role in determining a response to a given dose of biological agent. For example, several people may be exposed to dusts and pollens of chrysanthemum flowers (Chrysanthemum morifolium). However, only one may require treatment to correct bronchospasm and wheezing secondary to hypersensitivity to the naturally occurring pyrethrin in the plant. 3-Nonspecificity of Laboratory Analysis When a patient exposed to a biological agent presents to a healthcare facility, rapid laboratory analysis to identify and quantify the agent is not readily available. In these cases, treatment plans will be influenced by exposure history, clinical presentation, and other laboratory indices. Ex.:Frequent liver and kidney function tests following ingestion of death cap (Amanita phalloides), a cyclopeptide-containing mushroom.  4- Specific Antidotes Few specific antidotes exist to treat exposures to biological agents. In a vast majority of these cases, close observation and conservative symptomatic and supportive care are the mainstays of therapy. Hospital pharmacies affiliated with regional poison control centers may serve as antidote depots. If a particular pharmaceutical is not stored in the center, referrals for emergency access from other sources such as pharmaceutical companies, zoos or aquariums can be quickly made.  4- Specific Antidotes A few notable antidotes for biologic toxins do exist. Their use is generally reserved for serious and life-threatening poisoning incidents. Ex.: 1-Physostigmine for severe anticholinergic complications from Datura stramonium or Atropa belladonna. 2-Pyridoxine for neurologic symptoms due to ingestion of monomethyl hydrazine mushrooms like Gyromitra esculenta. 3-Atropine to reverse cholinergic symptoms due to ingestion of muscarine-containing mushrooms like the Inocybe. 5. Need for Nonmedical Consultants In providing optimal care to the patient poisoned by medications and chemicals, the clinician may call upon the services of a number of other medical consultants. Biological intoxications are unique in that identification of the toxic specimen may require consultation with nonmedical professionals. 5. Need for Nonmedical Consultants Consider the indispensable value of the expertise rendered by a nonmedical consultant in the following scenarios: a mycologist to identify an unknown mushroom a botanist to identify an unknown wild plant specimen a florist or horticulturist to identify an unknown household plant Until such time as the biological specimen is identified precisely, the poison control center can formulate a management strategy. The treatment regimen can then be modified once the accurate identification of the substance is made.  Poisonous mushrooms classification Gastrointestinal Miscellaneous cytotoxic myotoxic irritant adverse Endocrine/ or neurotoxic metabolically toxic  Cytotoxic mushrooms Their main target organs are liver and kidneys. The toxins responsible for liver and renal damage are amanitins, aminohexadienoic acid and orellanine. These toxins are mainly produced by species in Amanita and Cortinarius.  Cytotoxic mushrooms Amanitins are cyclic peptides, which can be classified into three groups: amatoxins, phallotoxins and virotoxins. After eating an amanitin-producing mushroom, symptoms develop in four periods:  Symptoms 2-violent GIT dysfunction 1-latency period period 3-latent phase 4-deterioration period (6-12 h after ingestion) (48-72 h after ingestion) (72-96 h after ingestion) (6-48 h after ingestion) No obvious intense diarrhea, symptoms symptoms of acute symptoms. hepatic injury and renal abdominal pain, disappear, but the failure. and vomiting. toxins have already been absorbed in and attacked the liver and kidney.  Possible treatment for hepatotoxic agent Decontamination: Lavage (within 1 hour)/activated charcoal with cathartic Supportive Therapy: I.V. fluids, lactulose, neomycin for hepatic failure; vitamin K and fresh frozen plasma may be needed to treat coagulopathy Antidotes: High dose Penicillin G, silymarin I.V. infusion , cimetidine I.V. every 8 hours, thioctic acid and N-acetylcysteine (efficacy of each has been questioned). N-acetylcysteine therapy or silybin dihemisuccinate appear to be the most effective therapy.  Possible treatment for renal toxic agent Decontamination: Lavage (within 1 hour)/activated charcoal Supportive therapy: Isotonic fluids for rehydration; renal transplant may be required for renal failure; forced diuresis is not effective; furosemide may increase renal dysfunction. Enhanced elimination: Hemodialysis or charcoal hemoperfusion should be started as soon as possible to prevent renal failure. Drug Interaction Increased toxicity may occur with phenobarbital or furosemide  Neurotoxic mushrooms The known toxins are psilocybins, muscarines and isoxazoles. Toxins are mainly from Agaricales such as Amanita, and Psilocybe.  Neurotoxic mushrooms Psilocybin Psilocybe is the main genus Producing psilocybin. In humans, oral exposure of 10-20 mg of psilocybin could cause mood changes and hallucination. Mechanism of Toxic Action Contains psilocybin which is indole alkaloid similar to Lysergic acid diethylamide(LSD), possible serotonin agonists.  Symptoms CVS: Tachycardia, flushing, hypertension, Wolff-Parkinson-White syndrome CNS: Ataxia, chills, headache, dizziness, fever, seizures, visual hallucinogens GIT: Vomiting Genitourinary: Urinary incontinence Hematologic: Methemoglobinemia Neuromuscular & skeletal: Myalgias, weakness Ocular: Mydriasis  Treatment Decontamination: Lavage (within 1 hour)/activated charcoal with cathartic. Supportive therapy: Diazepam for panic attacks; chlorpromazine may be useful for treatment of hallucinations.  Neurotoxic mushrooms Muscarine Muscarine is a kind of quaternary ammonium compound which is structurally similar to acetylcholine. It can therefore stimulate peripheral muscarinic, cholinergic receptors and cause related neurotoxic symptoms. Muscarine was first discovered and characterized from Amanita muscaria. Of note, concentrations of muscarine in A. muscaria are extremely low (approximately 0.0003%) when compared to some species of Inocybe (0.1-0.33%). Amanita muscaria  Symptoms Respiratory: perspiration, breathlessness. GIT: abdominal pain, diarrhea, vomiting, polysialia (hypersalivation). CVS: bradycardia. Occular: blurred vision.  Treatment Decontamination: Lavage (within 1 hour)/activated charcoal with cathartic. Supportive Therapy: I.V. hydration with isotonic saline; Antidote: atropine I.V, only if significant signs of cholinergic crisis are present; benzodiazepines are indicated for treating seizures  Neurotoxic mushrooms Isoxazoles Isoxazoles are mainly produced from Amanita sp. , such as A. muscaria. Isoxazoles mainly work on the CNS by stimulating N-methyl-D- aspartate (NMDA) receptors or gama aminobutyric acid(GABA) receptor. After eating the mushrooms, within minutes to 3h symptoms appear and these include confusion, dizziness, tiredness, unawareness of time, and drowsiness. The duration of CNS poisoning is short. Benzodiazepines can help to reduce or cure symptoms.  Neurotoxic mushrooms Anticholinergic group Some Amanita sp. Such as Amanita crenulata produce Anticholinergic toxins (ibotenic acid and its decarboxylation product, muscimol), Mechanism of Toxic Action: Inebriation syndrome is due primarily to the toxin ibotenic acid and its decarboxylation product, muscimol; ibotenic acid is structurally related to the excitatory neurotransmitter glutamic acid while muscimol is related to the inhibitory neurotransmitter GABA; combined action of both toxins may explain the initial excitation and inebriation followed by the prolonged coma- like sleep seen with poisoning.  Symptoms CVS: Tachycardia, hypotension CNS: Delirium, dizziness, ataxia, seizures, euphoria, residual headaches, fever, coma, hyperthermia, visual hallucinations GIT: Vomiting (rare), Neuromuscular & skeletal: Myoclonus, fasciculations Ocular: Mydriasis Renal: Renal failure (within 1 week of ingestion)  Treatment Decontamination: Lavage (within 1 hour)/activated charcoal Supportive therapy: hemodialysis if renal failure develops Antidote(s) physostigmine should only be used for life-threatening anticholinergic crisis (I.V. over a 5 minute period); Diazepam can be utilized for delirium and for seizures.  Myotoxic mushrooms Myotoxic mushrooms are highly associated with symptoms of rhabdomyolysis and are mainly from Russula and Tricholoma. Russuphelins and cycloprop-2-ene carboxylic acid are the main myotoxic agents. In the beginning, people may feel tired or muscle pain, followed by rhabdomyolysis, hypertension, renal failure, hyperkalaemia and cardiovascular collapse. The exact mechanisms of rhabdomyolysis are not fully understood, so there is no effective antidote to cure rhabdomyolysis. Clinical cases showed that treatment of hemoperfusion (HP) together with hemodialysis (HD) can be effective in rhabdomyolysis mushroom poisonings.  Metabolic/endocrine and related toxicity mushrooms GABA-blocking mushroom, Gyromitra esculenta, is widely consumed in Europe. It must be boiled or dried before eating, since fresh morels are hepatotoxic and even carcinogenic. Gyromitrin is a slightly volatile and heat-sensitive liquid, so boiling and drying could reduce its concentration. Gyromitra esculenta symptoms developed are called “Gyromitra syndrome”, which include simple GIT disorders, hepatic and neurological seizures, and even death due to hepatic injury.  Metabolic/endocrine and related toxicity mushrooms Mechanism of Gyromitrin toxicity: it is hydrolyzed upon digestion to N-methyl-N-formylhydrazine (MFH) and monomethylhydrazine (MMH). MMH is an inhibitor of coenzyme pyridoxyl phosphate and gamma- aminobutyric acid in the CNS. MFH is believed to deplete hepatic cytochrome P450  Treatment Decontamination: Lavage (within 1 hour)/activated charcoal with cathartic Supportive therapy: I.V. fluids Antidotal therapy: 1. Methylene Blue 2. Pyridoxine I.V. for seizures Drug Interaction: Phenobarbital may have an enhanced effect due to interference of hepatic metabolism.  Metabolic/endocrine and related toxicity mushrooms Trichothecene mushrooms cause multi organ failure and has caused lethal poisonings in Japan and Korea. The toxic agent is trichothecene which can be found in Trichoderma cornu-damae. Trichoderma cornu-damae.  Metabolic/endocrine and related toxicity mushrooms Hypoglycaemic mushroom, Trogia venenata, called “little white” or “nail-like” mushroom. There are three toxic compounds found in T. venenata, two new amino acid toxins 2R-amino-4S-hydroxy-5- hexynoic acid and 2R-amino-5- hexynoic acid and one known toxin gama-guanidinobutyric acid. Trogia venenata  Metabolic/endocrine and related toxicity mushrooms It causes a rapid drop in blood glucose. Thus, the T. venenata- exposed persons generally encountered a sudden unexplained death which was characterized by sudden loss of consciousness during normal activities. Trogia venenata  Gastrointestinal irritant mushrooms Poisoning by these mushroom groups is rarely fatal. There are many mushroom genera which can cause gastrointestinal poisoning, such as Chlorophyllum, and Entoloma. The specific toxins that cause these gastrointestinal effects have not been identified. with the exception of bolesatine and bolevenine, glycoproteins isolated from Rubroboletus satanas and Sutorius venenatus respectively.  Symptoms CVS: Pallor CNS: Fatigue, drowsiness, headache, chills. GIT (within 3 hours): Nausea, vomiting, watery diarrhea progressing to bloody diarrhea, abdominal pain. Neuromuscular & skeletal: Myalgias.  Treatment Decontamination: Activated charcoal Supportive therapy: Isotonic fluids for rehydration; symptoms usually resolve within 24 hours.  Miscellaneous adverse mushrooms Paxillus involutus , known as poison pax or brown rollrim, is an important ectomycorrhizal fungus and also a lethal mushroom which could cause autoimmune hemolytic poisoning. The toxin is unknown at present..  Miscellaneous adverse mushrooms Photosensitive dermatitis caused by Bulgaria inquinans due to the presence of Diisobutyl phthalate in this mushroom. the patient’s cells will become more sensitive under sunlight, and the skin will present dermatitis symptoms such as sunburn, a painful stinging sensation and itchiness. the poisoning usually occurs with other symptoms including nausea, vomit, abdominal pain, and diarrhea. Effective treatments including emetic and gastric lavage Exposure to the sunlight should be avoided, Antibiotic and antiallergic could be used as treatment.  Miscellaneous adverse mushrooms Antabuse-like reaction caused by Coprinus atramentarius which produces coprine Mechanism of Toxic Action:The metabolite of coprine, 1- aminocyclopropanol, inhibits aldehyde dehydrogenase and thus produces an antabuse-like reaction when consumed with alcohol  Symptoms CVS: Flushing, cardiovascular collapse, myocardial infarction, chest pain CNS: Dizziness, headache, seizures GIT: Nausea, vomiting, metallic taste, Hepatitis Neuromuscular & skeletal: Paresthesia Ocular: Retrobulbar neuritis, nystagmus Respiratory: Dyspnea Miscellaneous: Diaphoresis  Treatment Decontamination: Lavage (within 1 hour)/activated charcoal. management of disulfiram reaction: support measures to restore blood pressure (pressors and fluids); monitor for hypokalemia; metoclopramide or prochlorperazine can be used for vomiting. Antidote(s):Norepinephrine is the preferred agent; use of 4-methylpyrazole is investigational. Dopamine is not useful to treat disulfiram-ethanol induced hypotension. Case 1 A 16-year-old boy presents with abdominal pain, vomiting, and dizziness. He was hiking in the woods 8 hours ago when he ate some mushrooms he found. Laboratory testing reveals elevated liver enzymes. Inhibition of which of the following is responsible for the patient's condition? A. DNA helicase B. RNA polymerase II C. DNA topoisomerase II D. RNA polymerase III Case 1 A 16-year-old boy presents with abdominal pain, vomiting, and dizziness. He was hiking in the woods 8 hours ago when he ate some mushrooms he found. Laboratory testing reveals elevated liver enzymes. Inhibition of which of the following is responsible for the patient's condition? A. DNA helicase B. RNA polymerase II C. DNA topoisomerase II D. RNA polymerase III