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MUSHROOMS-MUSCIMOL/IBOTENIC ACID

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The toxins ibotenic acid, muscimol, and muscazone are found in certain species of mushrooms throughout the world. The 3 toxins are related and are all isoxazole derivatives.
    B) The concentration of these toxins is variable, depending on the specific specimen, environment, location, and time of year.
    C) The known pharmacologic properties of ibotenic acid and muscimol do NOT explain all the effects observed with A. muscaria, and there are most likely other still unidentified compounds involved.
    D) Active Ingredients in this class of mushroom:
    1) Ibotenic acid
    2) Muscimol
    3) Muscazone

Specific Substances

    A) POSSIBLE SPECIES
    1) Amanita citrina - "False Death Cap"
    2) Amanita cokeri (suspected)
    3) Amanita cernulata (suspected)
    4) Amanita cothurnata - "Booted Amanita"
    5) Amanita frostiana - "Frost's Amanita"
    6) Amanita gemmata - "Gemmed Amanita", "Jonquil Amanita"
    7) Amanita ibotengutake
    8) Amanita muscaria, "Fly Agaric", "Soma"
    9) Amanita pantherina, "Panther", "Panther Amanita", "Panther cap"
    10) Amanita strobiliformis (Japan)
    11) Isoxazoles
    12) Tricholoma muscarium (Japan)
    13) False Death Cap - "Common name for Amanita citrina "
    14) Booted Amanita - "Common name for Amanita cothurnata "
    15) Frost's Amanita - "Common name for Amanita frostiana "
    16) Gemmed Amanita - "Common name for Amanita gemmata"
    17) Jonquil Amanita - "Common name for Amanita gemmata"
    18) Fly Agaric - "Common name for Amanita muscaria "
    19) Soma - "Common name for Amanita muscaria "
    20) Panther, Panther cap - "Common name for Amanita pantherina"
    21) Panther Amanita - "Common name for Amanita pantherina"

Available Forms Sources

    A) SOURCES
    1) Total isoxazoles (ibotenic acid, muscimol, and muscazone) in dried A. muscaria was estimated to be 180 mg/100 grams; in A. pantherina 460 mg/100 grams. The amounts of ibotenic acid in A. muscaria and A. pantherina were estimated by Takemoto to be 25 and 220 mg/100 g (dry weight). These values are variable depending on such factors as year and location of collection (Concon, 1988).
    2) Total isoxazole content of samples of A. muscaria collected in 1962 and 1966 in Switzerland during the summer, varied from 30 mg/100 grams to as high as 100 mg/100 grams (dry weight) (Concon, 1988).
    3) A. muscaria does NOT contain muscarine in large enough amounts to produce symptoms of cholinergic toxicity.
    4) Toxic effects of A. muscaria have been retained in dried specimens for a period of 5 to 7 years.
    B) USES
    1) Many people intentionally ingest these mushrooms seeking a hallucinatory experience.
    2) An extract of ibotenic acid has been found to be almost 20 times more powerful than monosodium glutamate as a flavor enhancer. A derivative of muscimol is presently being used in Japan as a pesticide.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Mushrooms containing muscimol and ibotenic acid are usually ingested intentionally by individuals seeking the hallucinatory effects. Muscimol and ibotenic acid are found in Amanita muscaria, Amanita pantherina, Amanita gemmata, as well as other Amanita species. These mushrooms are rarely ingested inadvertently by amateur mushroom hunters, as most have a very distinctive appearance, but are occasionally ingested by children exploring their environment.
    B) TOXICOLOGY: Ibotenic acid is structurally similar to the stimulatory neurotransmitter glutamate and causes agitation, confusion, visual changes, myoclonus, and seizures. Ibotenic acid is decarboxylated-forming muscimol, which is structurally similar to gamma-aminobutyric acid (GABA). Muscimol causes CNS depression, sedation, and ataxia. Amanita muscaria contains more excitatory ibotenic acid, causing confusion and agitation more often. In contrast, Amanita pantherina contains more inhibitory muscimol, causing coma more often.
    C) EPIDEMIOLOGY: Intentional ingestions of these mushrooms are common. Inadvertent ingestion is rare. These mushrooms are commonly found throughout the United States and Europe. They are commonly found in wooded areas, especially conifer forests, in the spring and fall.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Initially, patients may experience significant gastrointestinal irritation with abdominal pain and self-limited nausea and vomiting. Muscle spasm/cramps may also occur. Both CNS depression, anxiety or agitation are possible. Tachycardia is common in agitated patients.
    2) SEVERE TOXICITY: Severely intoxicated patients may have myoclonus, seizures, profound neuromuscular agitation, paranoia, visual misinterpretation (changes in color vision or seeing trails of light), and delirium. Seizures may be more common in children.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) No significant changes in pulse rate or blood pressure.

Laboratory Monitoring

    A) No diagnostic testing is necessary in the vast majority of patients.
    B) If the history is unclear and the patient has altered mentation or severe vomiting, monitor serum electrolytes and blood glucose.
    C) In patients with profound neuromuscular agitation, a serum creatinine kinase can be drawn to screen for rhabdomyolysis.
    D) If the history is unclear or if trauma is present, CT of the head should be considered.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Supportive care is the mainstay of care for patients ingesting ibotenic acid/muscimol containing mushrooms. Antiemetics and fluid resuscitation should be given for patients with significant gastrointestinal irritation. Benzodiazepines may be given for agitated behavior though this is rarely necessary.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Seizures should be treated with IV benzodiazepines. Add propofol or phenobarbital if seizures persist.
    C) DECONTAMINATION
    1) PREHOSPITAL: No prehospital decontamination is indicated.
    2) HOSPITAL: Patients that present within several hours without significant nausea and vomiting may be given oral activated charcoal.
    D) AIRWAY MANAGEMENT
    1) Ibotenic acid and muscimol do not cause respiratory depression; however, patients that ingest multiple CNS depressants in addition to these mushrooms may require airway management for airway protection. Patients that have multiple seizures should be intubated for airway protection.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION PROCEDURE
    1) There is no role for extracorporeal elimination.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients or those with only mild gastrointestinal irritation can be managed at home if the mushroom identification is confirmed, there are no unidentified or more toxic mushrooms involved, and the ingestion was not a self-harm attempt.
    2) OBSERVATION CRITERIA: Patients who are symptomatic and those with self-harm attempts should be referred to a healthcare facility for evaluation.
    3) ADMISSION CRITERIA: Patients very rarely require admission. Patients that require airway management or those that have seizures should be admitted.
    4) CONSULT CRITERIA: Substance abuse counseling should be given to patients who intentionally ingest mushrooms. Consult a poison center or mycologist for assistance with mushroom identification. Consult a medical toxicologist or poison center in patients with moderate to severe symptoms.
    H) PITFALLS
    1) Patients with seizures that do not receive benzodiazepines may have recurrence of seizures. Over-sedation of patients with mild symptoms may lead to prolonged CNS depression and subsequently, a prolonged hospital stay. Mushrooms sold for recreational use may contain other recreational drugs. Patients may ingest other, more toxic mushrooms simultaneously.
    I) TOXICOKINETICS
    1) Symptom onset is usually within 30 to 120 minutes, peak within 2 to 3 hours and last up to 12 hours. Techniques to concentrate the toxins, such as steeping a tea, may lead to more rapid onset and peak of symptoms.
    J) DIFFERENTIAL DIAGNOSIS
    1) Ingestion of other hallucinogenic substances such as lysergic acid diethylamide (LSD), psilocybin mushrooms, peyote, or phencyclidine can be considered. Ingestion of other GABAergic agents, such as benzodiazepines or alcohol can cause similar CNS depression and ataxia. Psychiatric conditions should be considered in patients with auditory hallucinations or in patients with symptoms that are prolonged. Trauma and intracranial should be considered if the history of ingestion in unclear.

Range Of Toxicity

    A) TOXICITY: Symptoms can vary greatly and one cap has been shown to contain enough toxin to cause clinical toxicity. The toxic threshold is about 6 mg of muscimol and 30 to 60 mg of ibotenic acid. These amount are potentially available in a single specimen of A. muscaria or A. pantherina.

Clinical Effects

Summary Of Exposure

    A) USES: Mushrooms containing muscimol and ibotenic acid are usually ingested intentionally by individuals seeking the hallucinatory effects. Muscimol and ibotenic acid are found in Amanita muscaria, Amanita pantherina, Amanita gemmata, as well as other Amanita species. These mushrooms are rarely ingested inadvertently by amateur mushroom hunters, as most have a very distinctive appearance, but are occasionally ingested by children exploring their environment.
    B) TOXICOLOGY: Ibotenic acid is structurally similar to the stimulatory neurotransmitter glutamate and causes agitation, confusion, visual changes, myoclonus, and seizures. Ibotenic acid is decarboxylated-forming muscimol, which is structurally similar to gamma-aminobutyric acid (GABA). Muscimol causes CNS depression, sedation, and ataxia. Amanita muscaria contains more excitatory ibotenic acid, causing confusion and agitation more often. In contrast, Amanita pantherina contains more inhibitory muscimol, causing coma more often.
    C) EPIDEMIOLOGY: Intentional ingestions of these mushrooms are common. Inadvertent ingestion is rare. These mushrooms are commonly found throughout the United States and Europe. They are commonly found in wooded areas, especially conifer forests, in the spring and fall.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Initially, patients may experience significant gastrointestinal irritation with abdominal pain and self-limited nausea and vomiting. Muscle spasm/cramps may also occur. Both CNS depression, anxiety or agitation are possible. Tachycardia is common in agitated patients.
    2) SEVERE TOXICITY: Severely intoxicated patients may have myoclonus, seizures, profound neuromuscular agitation, paranoia, visual misinterpretation (changes in color vision or seeing trails of light), and delirium. Seizures may be more common in children.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) No significant changes in pulse rate or blood pressure.
    3.3.2) RESPIRATIONS
    A) WITH POISONING/EXPOSURE
    1) Breathing is slow and regular, as in deep sleep.
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) Blood pressure is usually normal.
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) Pulse is usually normal but tachycardia and bradycardia can occur.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Alternating mydriasis and miosis have been reported (Benjamin, 1992).
    2) Changes in visual perception developed in a man who ingested 2 or 3 Amanita ibotengutake mushrooms (Hiroshima et al, 2010).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) One case is reported in which a patient developed ventricular fibrillation (Lincoff & Mitchel, 1977).
    B) PALPITATIONS
    1) WITH POISONING/EXPOSURE
    a) Palpitations developed in a man who ingested 2 or 3 Amanita ibotengutake mushrooms (Hiroshima et al, 2010).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY SYMPTOM
    1) WITH POISONING/EXPOSURE
    a) LACK OF EFFECT
    1) Respirations are NOT usually affected (Bosman et al, 1965).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 48-year-old man developed vomiting 30 minutes after ingesting Amanita muscaria. He was found comatose having myoclonus and seizure like activity 3 hours after ingestion. He received benzodiazepines and activated charcoal and 10 hours after ingestion, he awoke and became completely orientated. His condition deteriorated again 18 hours after ingestion and he became confused and uncooperative. He experienced paranoia with visual and auditory hallucinations that lasted for 5 days. Following supportive care, his symptoms resolved on day 6 (Brvar et al, 2006).
    b) Seizures are rare except in children ingesting a large amount (Lewis, 1996; Goldfrank, 1998). CNS effects in children may last up to 12 hours. Tonic/clonic seizures occurred in 2 of 11 patients reported by Benjamin (1992)(Benjamin, 1992). Five of these 11 had muscle fasciculations or myoclonic jerking. These symptoms will usually resolve within 6 to 9 hours without therapy.
    c) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, seizures were reported in 4 of 32 cases of Amanita muscaria poisoning and 2 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    B) COMA
    1) WITH POISONING/EXPOSURE
    a) Initial excitation often leaves the patient becoming stuporous and then comatose. Patients may alternate between severe lethargy and agitated abnormal behavior (Benjamin, 1992). Children are particularly susceptible to CNS effects after ingesting large amounts and may experience seizures followed by coma, lasting up to 12 hours (Lewis, 1996).
    b) Often the victim experiences somnolence which he/she is extremely difficult to arouse. Some individuals have visions during this period (Ammirati et al, 1985). Drowsiness to deep sleep or even coma terminates the episode which usually lasts from 4 to 8 hours.
    c) CASE REPORT: A 48-year-old man developed vomiting 30 minutes after ingesting Amanita muscaria. He was found comatose having myoclonus and seizure like activity 3 hours after ingestion. He received benzodiazepines and activated charcoal and 10 hours after ingestion, he awoke and became completely orientated. His condition deteriorated again 18 hours after ingestion and he became confused and uncooperative. He experienced paranoid psychosis with visual and auditory hallucinations that lasted for 5 days. Following supportive care, his symptoms resolved on day 6 (Brvar et al, 2006).
    d) CASE REPORT: Approximately 20 minutes after ingesting dried fly agaric Amanita muscaria (6 large caps) at a party, an 18-year-old girl experienced severe hallucinations and lost consciousness. The next day, she was admitted to the hospital because of weakness, fatigue and gastric pain. Following supportive care, she recovered (Satora et al, 2005).
    e) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, coma was reported in 2 of 32 cases of Amanita muscaria poisoning and 5 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    C) PSYCHOMOTOR AGITATION
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Babbling, confusion, screaming, irritability and hallucinations have been reported in children (Satora et al, 2006; Benjamin, 1992) and adults (Lewis, 1996; Goldfrank, 1998).
    b) Agitation and extreme talkativeness developed in a man who ingested 2 or 3 Amanita ibotengutake mushrooms (Hiroshima et al, 2010).
    c) Dizziness, ataxia, and euphoria may progress into hyperkinetic activity, muscle jerks and spasms, and delirium. Poisoning in adults is rarely severe, but some degree of protective care may be required in patients who experience manic excitement (Carter et al, 1983).
    d) Symptoms usually begin with drowsiness quickly followed by a state of confusion (Bosman et al, 1965).
    e) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, agitation was reported in 20 of 32 cases of Amanita muscaria poisoning and 5 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    D) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache may persist for several days (Carter et al, 1983).
    E) NUMBNESS
    1) WITH POISONING/EXPOSURE
    a) Numbness of extremities developed in a man who ingested 2 or 3 Amanita ibotengutake mushrooms (Hiroshima et al, 2010).
    F) DROWSY
    1) WITH POISONING/EXPOSURE
    a) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, somnolence was reported in 13 of 32 cases of Amanita muscaria poisoning and 5 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    G) MYOCLONUS
    1) WITH POISONING/EXPOSURE
    a) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, myoclonus was reported in 6 of 32 cases of Amanita muscaria poisoning and 6 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    H) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, confusion was reported in 26 of 32 cases of Amanita muscaria poisoning and 8 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS EFFECTS
    a) Following a probable ingestion of Amanita pantherina, a puppy presented to a medical facility in lateral recumbency and was semi-comatose, with opisthotonus, right lateral strabismus, paddling and exhibited chewing movements. Another puppy was quadraparetic and depressed, with lateral strabismus. Pupils were severely miotic in both animals (Naude & Berry, 1997).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting may occur (Hiroshima et al, 2010; Brvar et al, 2006; Satora et al, 2006; Bosman et al, 1965), but severe vomiting is rare (Bosman et al, 1965). Abdominal discomfort may occur (Lewis, 1996).
    b) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, vomiting was reported in 18 of 32 cases of Amanita muscaria poisoning and 11 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea has been reported following the ingestion of Amanita pantherina (Satora et al, 2006).
    b) In a retrospective study of 49 patients admitted for mushroom intoxication during a 33-year period, diarrhea was reported in 5 of 32 cases of Amanita muscaria poisoning and 4 of 17 cases of Amanita pantherina poisoning (Vendramin & Brvar, 2014).
    C) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain has been reported following the ingestion of Amanita pantherina (Satora et al, 2006).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) CRAMP
    1) WITH POISONING/EXPOSURE
    a) Muscle spasm/cramps may occur (Shaw, 1994).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No diagnostic testing is necessary in the vast majority of patients.
    B) If the history is unclear and the patient has altered mentation or severe vomiting, monitor serum electrolytes and blood glucose.
    C) In patients with profound neuromuscular agitation, a serum creatinine kinase can be drawn to screen for rhabdomyolysis.
    D) If the history is unclear or if trauma is present, CT of the head should be considered.

Methods

    A) CHROMATOGRAPHY
    1) Muscimol and ibotenic acid have been quantitated by amino acid analyzer, and their trimethylsilyl derivatives can be detected using gas chromatography.
    2) In one study, liquid chromatography-mass spectrometry was a sensitive and specific method to isolate and identify Amanita muscaria and amanita pantherina in urine of intoxicated patients. Limit of detections for ibotenic acid, muscimol, and muscarine were 50 ng/mL, 40 ng/mL, and 3 ng/mL, respectively (Merova et al, 2008).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients very rarely require admission. Patients that require airway management or those that have seizures should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients or those with only mild gastrointestinal irritation can be managed at home if the mushroom identification is confirmed, there are no unidentified or more toxic mushrooms involved, and the ingestion was not a self-harm attempt.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Substance abuse counseling should be given to patients who intentionally ingest mushrooms. Consult a poison center or mycologist for assistance with mushroom identification. Consult a medical toxicologist or poison center in patients with moderate to severe symptoms.
    6.3.1.4) PATIENT TRANSFER/ORAL
    A) Patients who are exhibiting severe sensory symptoms should be transferred to psychiatric facilities capable of handling subdued environment and psychiatric support.
    B) The manic or delirium phase of intoxication can usually be handled without drug intervention by utilizing reassurance and restraint (Hatfield, 1979).
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients who are symptomatic and those with self-harm attempts should be referred to a healthcare facility for evaluation.

Monitoring

    A) No diagnostic testing is necessary in the vast majority of patients.
    B) If the history is unclear and the patient has altered mentation or severe vomiting, monitor serum electrolytes and blood glucose.
    C) In patients with profound neuromuscular agitation, a serum creatinine kinase can be drawn to screen for rhabdomyolysis.
    D) If the history is unclear or if trauma is present, CT of the head should be considered.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) PREHOSPITAL: No prehospital decontamination is indicated.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY: Patients that present within several hours without significant nausea and vomiting may be given oral activated charcoal.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) No diagnostic testing is necessary in the vast majority of patients.
    2) If the history is unclear and the patient has altered mentation or severe vomiting, monitor serum electrolytes and blood glucose.
    3) In patients with profound neuromuscular agitation, a serum creatinine kinase can be drawn to screen for rhabdomyolysis.
    4) If the history is unclear or if trauma is present, CT of the head should be considered.
    B) PSYCHOMOTOR AGITATION
    1) ANXIETY/AGITATION: Diazepam may be useful in patients with serious agitation (Benjamin, 1992).
    2) INDICATION
    a) If patient is severely agitated, sedate with IV benzodiazepines.
    3) DIAZEPAM DOSE
    a) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    4) LORAZEPAM DOSE
    a) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
    b) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    5) Extremely large doses of benzodiazepines may be required in patients with severe intoxication in order to obtain adequate sedation. Titrate dose to clinical response and monitor for hypotension, CNS and respiratory depression, and the need for endotracheal intubation.
    C) SEIZURE
    1) Benzodiazepines such as DIAZEPAM are likely the most appropriate agents used to treat seizures or the excitatory symptoms but severe respiratory depression due to potentiation of the muscimol-induced GABA effect may occur (Page, 1980; Naude & Berry, 1997).
    2) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    3) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    4) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    5) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    6) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    7) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

Enhanced Elimination

    A) SUMMARY
    1) There is no role for extracorporeal elimination.

Abstracts

Case Reports

    A) OTHER
    1) MUSHROOM POISON CASE REGISTRY
    a) MUSHROOM POISON CASE REGISTRY
    1) Mushroom poisoning cases may be reported to the North American Mycological Association's Mushroom Poisoning Case Registry. Reporting is voluntary and patient confidentiality is maintained.
    2) Forms may be obtained from the website and completed forms or questions may be sent to:
    3) Dr. Michael W. Beug, PO Box 116, Husum, WA 98623; phone: (509) 493-2237
    4) Alternatively, reports may be submitted online at www.sph.umich.edu/~kwcee/mpcr. The website also contains a list of volunteers from different regions of North America willing to assist in the identification of mushrooms.
    B) ADULT
    1) In 1975, Chilton took an intentional ingestion of 93 mg of crystalline ibotenic acid dissolved in cold water. There were no immediate effects other than a taste sensation. By 1.5 hours post exposure he noticed a slight tendency to wobble when walking.
    a) The unsteadiness continued to increase until by 3 hours post exposure he felt as though any sudden movement might cause his head to "roll off his shoulders". At 3.5 hours post exposure he began noting the feeling of pressure at the base of his skull.
    b) He also had the feeling of being pressed down by a great weight distributed uniformly over his body. His penmanship also deteriorated noticeably, but his thought processes and speech articulation remained unaffected. At 4 hours post, muscle twitches began first in the fingers then in the legs.
    c) Very mild visual spasms soon followed and his field of vision narrowed. The field of vision began to rotate slowly and sometimes to slide right, left, up or down. At no time did he note hallucinations. At 6 hours post, reading was laborious as the printed words appeared to move aimlessly.
    d) This period dominated by ever increasing disequilibrium suddenly terminated in a deep but short sleep of approximately 20 minutes in duration. Upon awakening he vomited briefly and immediately sank back into heavy, drugged sleep from which he was aroused about an hour later.
    e) He continued to suffer from bouts of sleep. At 10 hours post exposure he awoke fully. The dizziness gradually disappeared, and all sensations were normal by 11.5 hours post exposure (Chilton, 1975).
    2) Reports of ingestion of A. pantherina showed the following symptoms: dizziness, impaired vision (apparent remoteness of near objects), hysteria, an intoxicated feeling, loss of coordination, inability to think and speak coherently, loss of consciousness, and in one instance death of a man with a weak heart (Lincoff & Mitchel, 1977).
    C) PEDIATRIC
    1) A 7.5-year-old boy who ingested two large A. pantherina raw, showed the following symptomatology: the child acted drunk and could neither walk straight nor talk clearly; his speech became slurred. After 4 hours post ingestion he fell into a deep sleep for about 0.5 hour, then awakened, rolled about, and ran through the house screaming. The next day, after recovering, the child related 8 different hallucinatory visions (Lincoff & Mitchel, 1977).
    a) In Massachusetts a cooked meal of 8 specimens of A. gemmata caused abdominal pain, nausea, vomiting, diarrhea, and cardiovascular manifestations. The patient developed ventricular fibrillation.
    b) In another case a 2-year-old child died after becoming irritable, then listless, then suffered a seizure. In 1967, A. gemmata caused fatalities in Chile (Lincoff & Mitchel, 1977).

Range Of Toxicity

Summary

    A) TOXICITY: Symptoms can vary greatly and one cap has been shown to contain enough toxin to cause clinical toxicity. The toxic threshold is about 6 mg of muscimol and 30 to 60 mg of ibotenic acid. These amount are potentially available in a single specimen of A. muscaria or A. pantherina.

Minimum Lethal Exposure

    A) Death from ingesting mushrooms containing these toxins is rare. Fatality rates are thought to be less than 1%. However, deaths from the ingestion of muscimol have been reported when large quantities have been ingested or when the victim might be suffering from some organic illness (Ammirati et al, 1985a).

Maximum Tolerated Exposure

    A) ACUTE
    1) The toxic threshold is about 6 mg of muscimol and 30 to 60 mg of ibotenic acid. These amounts are potentially available in a single specimen of A. muscaria or A. pantherina (Chilton, 1978).
    2) Two to 4 Amanita muscaria mushrooms have been ingested for hallucinogenic effect, and 20 large Amanita muscaria have been ingested with survival. The toxicity will depend upon the toxicity of the mushrooms and the susceptibility of the individual; a smaller number may be fatal.
    3) As much as 10 times the amount of isoxazoles have been reported in specimens collected in spring/summer compared to autumn (Satora et al, 2006).
    4) In human volunteers, effects were measurable approximately one hour after ingestion of 7.5 to 10 mg of muscimol or 50 to 90 mg of ibotenic acid, and continued for 3 to 4 hours. (Spoerke & Rumack, 1994)

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) IBOTENIC ACID
    1) LD50- (ORAL)MOUSE:
    a) 38 mg/kg ((RTECS, 2000))
    2) LD50- (ORAL)RAT:
    a) 129 mg/kg ((RTECS, 2000))
    B) MUSCIMOL
    1) LD50- (ORAL)MOUSE:
    a) 22 mg/kg ((RTECS, 2000))
    2) LD50- (ORAL)RAT:
    a) 45 mg/kg ((RTECS, 2000))

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Ibotenic acid is structurally similar to glutamic acid and mimics its effects in animals. Ibotenic acid is rapidly converted to muscimol, which structurally resembles GABA.
    B) Muscimol has a high affinity for GABA receptor sites and imitates the action of GABA in animals and humans, inhibiting and controlling the recruitment and multiplication of nerve impulses mediated by many of the positive neurotransmitters (Page, 1984).
    C) Not all the toxins have been identified. Neither pure muscimol or ibotenic acid produce the nausea and vomiting that frequently occurs after ingesting A. muscaria.

Toxicologic Mechanism

    A) The isoxazoles (Ibotenic acid, Muscimol, and Muscazone) cause most of the symptoms. Pantherin, Stizolobic acid and Stizolobinic acid (L-dopa oxidation products) and Tricholomic acid have similar chemical structures and physiological effects.
    B) These effects are primarily on the CNS where these compounds apparently compete with the normal transmitter, gamma-aminobutyric acid (GABA), and cause the hallucinogenic symptoms. The peripheral effects, relatively slight, are usually more anticholinergic than cholinergic. There is NO evidence that these mushrooms contain significant amounts of atropine (pilzatropine), hyoscyamine, or stramonium.
    C) In one study, comparing the effects of Amanita muscaria and Amanita pantherina, it was determined that Amanita muscria has more excitatory ibotenic acid, causing confusion and agitation more often. In contrast, Amanita pantherina has more inhibitory muscimol, causing coma more often (Vendramin & Brvar, 2014).

Physicochemical

Physical Characteristics

    A) These compounds act as flavor enhancers and thus produce an unusual aftertaste.

Molecular Weight

    A) MUSCIMOL: 114.12
    B) IBOTENIC ACID: 176.15

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) A litter of nine 4.5-week-old pups ingested "mushrooms" identified as Amanita pantherina. Some animals experienced opisthotonus and ataxia and died in 1 to 3 hours. The rest experienced intermittent seizures over the next 12 hours, and then recovered by 17 hours after being treated with atropine (Hunt & Funk, 1977).
    1) NOTE: A. muscaria does NOT contain muscarine in large enough amounts to produce symptoms of cholinergic toxicity (Concon, 1988).
    2) Do NOT give atropine, unless definite cholinergic symptoms are present.
    B) A suspected case of Amanita pantherina poisoning in three German shepherd puppies has been reported. A severe, transient neurological disorder with signs/symptoms of ataxia, disorientation, muscle weakness, lethargy and paralysis, was reported in the puppies. Pupils were severely miotic (Naude & Berry, 1997).
    11.1.13) OTHER
    A) OTHER
    1) FREQUENCY - Frequency of animal poisoning with these mushrooms has been low (Humphreys, 1988; Beasley et al, 1989); Amanita species are usually implicated.
    2) CLINICAL PROGRESSION - Some animals that survive the acute gastrointestinal signs may experience jaundice, renal shutdown, seizures, and coma two to four days after exposure. Initial signs may NOT occur for 6 to 48 hours after exposure (Beasley et al, 1989).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Treat the same as for human exposure.
    2) SUMMARY
    a) Begin treatment immediately.
    b) Keep animal warm and do not handle unnecessarily.
    c) Remove the patient and other animals from the source of contamination or remove dietary sources.
    3) Treatment should always be done on the advice and with the consultation of a veterinarian.
    4) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
    5) ASPCA ANIMAL POISON CONTROL CENTER
    a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) EMESIS/GASTRIC LAVAGE -
    1) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
    2) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
    3) DOGS AND CATS
    a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
    b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.
    4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.
    b) ACTIVATED CHARCOAL/CATHARTIC -
    1) ACTIVATED CHARCOAL: Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    2) CATHARTIC: Administer a dose of a saline or sorbitol cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    3) ACTIVATED CHARCOAL/HORSES: Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water.
    4) ACTIVATED CHARCOAL/RUMINANTS: Administer 2 to 9 grams/ kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube. Sheep may be given 0.5 kilogram charcoal in slurry.
    5) CATHARTICS/HORSES: Mineral oil is administered 30 minutes after activated charcoal. DOSE: 4 to 6 liters in adult horses and 1 to 4 liters in neonates or foals.
    a) Magnesium sulfate: 0.2 to 0.9 grams/kilogram (500 grams for adults).
    b) The sulfate laxatives are especially effective when given 30 to 45 minutes after mineral oil administration.
    c) Carbachol (lentin): administer 1 milligram to an adult.
    6) CATHARTICS/RUMINANTS & SWINE: Adult cattle: administer 500 grams sodium or magnesium sulfate. Other ruminants and swine: administer 1 to 2 grams/kilogram.
    a) The sulfate laxatives are especially effective when given 30 to 45 minutes after cathartic administration.
    b) Mineral oil: Do not administer within 30 minutes of activated charcoal. DOSE: small ruminants and swine, 60 to 200 milliliters; cattle, 0.5 to 1 gallon.
    c) Magnesium oxide: (Milk of Magnesia) Small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os.
    d) Give these solutions via stomach tube and monitor for aspiration.
    11.2.5) TREATMENT
    A) GENERAL TREATMENT
    1) MAINTAIN VITAL FUNCTIONS - as necessary.
    2) ATROPINE
    a) A. muscaria does NOT contain muscarine in large enough amounts to produce symptoms of "cholinergic overdrive", and in fact the automatic administration of atropine as an antidote will only significantly add to the "anticholinergic overdrive" toxic effects of ibotenic acid and muscimol (Concon, 1988).
    b) Do NOT give atropine, unless definite cholinergic symptoms are present.
    3) FLUID REPLACEMENT -
    a) Begin electrolyte and fluid therapy with isotonic solutions as needed at maintenance doses (66 milliliters solution/kilogram body weight/day intravenously) or, in hypotensive patients, at high doses (up to shock dose 60 milliliters/kilogram/hour). Monitor for urine production and pulmonary edema.
    b) HORSE: Administer electrolyte and fluid therapy as needed. Maintenance dose of intravenous isotonic fluids: 10 to 20 milliliters/ kilogram per day. High dose for shock: 20 to 45 milliliters/kilogram/hour.
    1) Monitor for packed cell volume, adequate urine output and pulmonary edema. Goal is to maintain a urinary flow of 0.1 milliliters/kilogram/minute (2.4 liters/hour for an 880 pound horse).
    c) CATTLE: Administer electrolyte and fluid therapy, orally or parenterally as needed. Maintenance dose of intravenous isotonic fluids for calves and debilitated adult cattle: 140 milliliters/kilogram/day. Dose for rehydration: 50 to 100 milliliters/kilogram given over 4 to 6 hours.
    4) LABORATORY -
    a) Monitor urine for hematuria.
    b) This agent may cause hepatotoxicity. Monitoring liver function tests is suggested for patients with significant exposure.
    5) MONITORING -
    a) Admit all symptomatic patients and begin treatment.
    b) Observe asymptomatic patients for 24 hours in the primary care clinic.
    6) FOLLOW-UP -
    a) Instruct the owner to return for a follow up appointment at which physical examination and appropriate laboratory tests will be repeated.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Treat the same as for human exposure.
    2) SUMMARY
    a) Begin treatment immediately.
    b) Keep animal warm and do not handle unnecessarily.
    c) Remove the patient and other animals from the source of contamination or remove dietary sources.
    3) Treatment should always be done on the advice and with the consultation of a veterinarian.
    4) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
    5) ASPCA ANIMAL POISON CONTROL CENTER
    a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) EMESIS/GASTRIC LAVAGE -
    1) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
    2) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
    3) DOGS AND CATS
    a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
    b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.
    4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.
    b) ACTIVATED CHARCOAL/CATHARTIC -
    1) ACTIVATED CHARCOAL: Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    2) CATHARTIC: Administer a dose of a saline or sorbitol cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    3) ACTIVATED CHARCOAL/HORSES: Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water.
    4) ACTIVATED CHARCOAL/RUMINANTS: Administer 2 to 9 grams/ kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube. Sheep may be given 0.5 kilogram charcoal in slurry.
    5) CATHARTICS/HORSES: Mineral oil is administered 30 minutes after activated charcoal. DOSE: 4 to 6 liters in adult horses and 1 to 4 liters in neonates or foals.
    a) Magnesium sulfate: 0.2 to 0.9 grams/kilogram (500 grams for adults).
    b) The sulfate laxatives are especially effective when given 30 to 45 minutes after mineral oil administration.
    c) Carbachol (lentin): administer 1 milligram to an adult.
    6) CATHARTICS/RUMINANTS & SWINE: Adult cattle: administer 500 grams sodium or magnesium sulfate. Other ruminants and swine: administer 1 to 2 grams/kilogram.
    a) The sulfate laxatives are especially effective when given 30 to 45 minutes after cathartic administration.
    b) Mineral oil: Do not administer within 30 minutes of activated charcoal. DOSE: small ruminants and swine, 60 to 200 milliliters; cattle, 0.5 to 1 gallon.
    c) Magnesium oxide: (Milk of Magnesia) Small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os.
    d) Give these solutions via stomach tube and monitor for aspiration.

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