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BREVETOXINS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Red tides are caused by several non-protein, lipid soluble neurotoxins and hemolysins found in certain marine dinoflagellates such as Ptychodiscus brevis (formerly called Gymnodinium breve). Besides causing kills of large numbers of fish, these toxins produce various respiratory effects in man and other shore animals (Baden & Mende, 1982; Pierce, 1986). Humans become poisoned by consuming shellfish that have consumed the dinoflagellates containing brevetoxins. Possible sources of human poisoning include cockles, oysters, whelks and clams (Ishda et al, 1996; (Poli et al, 2000).
    B) These toxins appear to be primarily intracellular and do not leach out in appreciable amounts unless the cells disintegrate (Spiegelstein et al, 1973; Shilo, 1967).
    C) Saxitoxin type poisoning (Paralytic Shellfish Poisoning) may also be seen during "red tides" (Martin & Martin, 1976).
    D) BREVETOXIN CONTAINING ORGANISMS
    1) Karenia brevis (formerly Gymnodinium breve, formerly Ptychodiscus brevis)
    2) Karenia spp.
    3) Chatonella spp.
    4) Fibrocapsa japonica
    5) Ptychodiscus brevis (formerly Gymnodinium breve)
    6) Ptychodiscus veneficum (formerly Gymnodinium veneficum)

Specific Substances

    A) PbTx-1
    1) Brevetoxin A
    2) BTX-A
    3) T46
    4) References: Poli et al, 1986
    PbTx-2
    1) Brevetoxin B
    2) GB-2
    3) BTX-BT34
    4) T-Ald
    5) GbTX-B
    6) T2
    7) T47
    8) References: Lin et al, 1981; Nakanishi, 1985;
    9) Chou & Shimizu, 1982; Lin et al, 1981
    PbTx-3
    1) T17 GB-3T-Alc
    2) References: Chou & Shimizu, 1982; Baden et
    3) al, 1984
    PbTx-4
    1) GB-4
    PbTx-5
    1) GB-5
    PbTx-6
    1) GB-6
    PbTx-7
    1) GB-7
    PbTx-8
    1) Brevetoxin C (a chloromethyl ketone
    2) derivative of brevetoxin B)
    3) BTX-C
    CAUSATIVE ORGANISM
    1) Chatonella spp.
    2) Karenia spp.
    3) Karenia brevis
    4) Fibrocapsa japonica
    General Terms
    1) FISH POISONING, NEUROTOXIC SHELLFISH
    2) NEUROTOXIC SHELLFISH POISONING
    3) RED TIDE
    4) FLORIDA RED TIDE

Available Forms Sources

    A) FORMS
    1) TOXIN STRUCTURES - These toxins are an eleven member hetrocyclic oxygen containing fused ring system ending with an unsaturated lactone on one end and an unsaturated aldehyde at the other (brevetoxin B). T17 is identical except that there is an alcohol group in place of the aldehyde in brevetoxin B. There are several other similar toxins including a chlorine containing analog (brevetoxin A) and 2 polycyclic ethers (Pierce, 1986).
    2) Red tides are not always red, but may be brown, yellow, or green, depending upon the pigmentation of the causative organisms, and their depth and concentration (Sasner, 1973). These toxins are especially toxic to fish. It was estimated that 100 tons of fish per day were killed in a 1971 bloom off the coast of Florida (Sasner, 1973).
    B) SOURCES
    1) Brevetoxins are endotoxins found in the dinoflagellates, Ptychodiscus brevis, the agent which causes "red tides" in the Gulf of Mexico (Pierce, 1986). There are at least 8 brevetoxins produced by P. brevis (Baden et al, 1988).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. The Centers for Disease Control and Prevention (CDC) has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdc.gov.
    b) ACUTE SYMPTOMS (WITHIN 48 HOURS)
    1) GI: Abdominal pain, cramping, nausea, vomiting, diarrhea. RESP: Conjunctival irritation, rhinorrhea, nonproductive cough, bronchoconstriction, exacerbation of underlying respiratory conditions (ie, asthma). NEURO: Confusion, paresthesias of face, throat and extremities, ataxia, distorted sensorium, vertigo. CV: Bradycardia. HEENT: Headache, salivation, ocular irritation and pupil dilation. DERM: Skin or nasal irritation, rash, dermatitis, hives, lacrimation and cough. SEVERE TOXICITY: Seizures, coma, or respiratory arrest may develop.
    c) CHRONIC SYMPTOMS
    1) Unknown.
    d) FATALITY RATE
    1) No human deaths reported.
    e) TIME TO ONSET OF SYMPTOMS
    1) INGESTION: Less than one hour up to 24 hours after eating contaminated seafood.
    2) AEROSOL: Immediate respiratory irritation.
    3) DERMAL: Immediate to delayed skin and mucous membrane irritation; symptoms most often within a few hours.
    f) DURATION
    1) INGESTION: Typically 6 to 72 hours.
    2) AEROSOL: Symptoms typically resolve once exposure is discontinued; however respiratory symptoms may persist days to weeks in individuals with underlying respiratory conditions.
    3) DERMAL: Unknown.
    g) CAUSATIVE ORGANISM
    1) The following organisms may produce illness: Karenia brevis (formerly Gymnodinium breve, formerly Ptychodiscus brevis), Karenia spp., Chatonella spp., Fibrocapsa japonica, and other marine microalgae that produce brevetoxins.
    h) TOXIN
    1) Brevetoxins: a suite of polyether toxins (CAS 98225-48-0).
    i) VECTOR
    1) Contaminated bivalve shellfish including: scallops, clams, mussels and oysters; contaminated water, aerosols, or foams/scum near the shore.
    j) ROUTE OF EXPOSURE
    1) Eating contaminated shellfish, inhaling contaminated sea aerosols, or direct skin/mucous membrane contact with contaminated seawater or sea foam/scum near the shore during a bloom.
    k) MECHANISM
    1) Sodium channel mediated depolarization resulting in a stimulatory nervous effect.
    l) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Gulf of Mexico, US Southeastern and mid-Atlantic coasts, New Zealand.
    m) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisoning, scombroid fish poisoning, pesticide poisoning including: organophosphate poisoning, cholinesterase inhibitor poisoning, microbial food poisoning and food allergies; inhalation of chemical respiratory irritants or skin contact of chemical/biological irritants (including possibly cyanobacteria).
    n) DIAGNOSIS
    1) Clinical presentation, history of shellfish consumption and meal remnant assay (mouse bioassay, ELISA, HPLC-MS/MS) or specimen assay (ELISA or HPLC-MS/MS).
    o) SUSPECT CASE
    1) INGESTION: Consumption of shellfish and onset of neurologic symptoms with or without GI symptoms within 30 minutes to 24 hours.
    2) AEROSOL: Exposure to ocean aerosols and immediate onset of new, or exacerbation of existing, respiratory symptoms.
    3) DERMAL: Exposure to ocean waters or aerosols and immediate onset of new, or exacerbation of existing, skin or mucous membrane symptoms.
    p) CONFIRMED CASE
    1) Suspect case and verification of brevetoxin in clinical specimen OR verification of brevetoxin in shellfish meal remnant OR confirmed bloom of Karenia brevis or other brevetoxin-producing organism in a relevant geographic area.
    q) ANIMAL SENTINEL DATA
    1) Seabird, manatee and dolphin fatalities have been reported.
    r) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)
    0.2.4) HEENT
    A) WITH POISONING/EXPOSURE
    1) Contact with contaminated water may produce mydriasis, irritation, lacrimation, rhinorrhea, and sneezing in humans.
    2) Salivation was reported in animals.
    0.2.5) CARDIOVASCULAR
    A) WITH POISONING/EXPOSURE
    1) Bradycardia has been noted in humans.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Coughing, sneezing, and difficulty in breathing has occurred in man and animals. Severely poisoned animals die of respiratory arrest.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Typical effects include paresthesias of the face, lips, and extremities, dystaxias, a feeling of confusion, and a distorted sensorium. More serious cases may develop seizures or coma.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Cramping, abdominal pain, and diarrhea may occur.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Swimming in red tides may produce pruritus.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

    A) No specific laboratory tests are useful in diagnosis of brevetoxin intoxication.
    B) Confirmatory testing (LC-MS) may be performed to measure brevetoxin metabolites in human urine if indicated. Bioassays, ELISA, HPLC-MS/MC) techniques have been used to detect brevetoxin in research and food (eg, meal remnants).

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) DECONTAMINATION
    1) Emesis is not recommended due to potential seizures, coma, and respiratory arrest. Gastrointestinal decontamination is unlikely to be useful once symptoms have developed; however, brevetoxins are large, organic molecules which may be adsorbed to activated charcoal. INHALATION: Move patient to fresh air. Monitor respiratory function for respiratory tract irritation or bronchitis. Exposure may exacerbate underlying respiratory conditions (eg, asthma). DERMAL: Remove contaminated clothing and wash exposed areas with soap and water. Persistent symptoms may require examination by a physician. OCULAR: Rinse eye with copious amounts of warm water. Ongoing symptoms may require further examination and treatment.
    B) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Bradycardia may develop. Based on limited animal data, atropine was found to reverse the bronchoconstrictive and the bradycardic effects of brevetoxins. Atropine: Usual starting dose: Adult: 0.5 to 1 mg IV; repeat every 5 minutes if symptoms persist. Pediatric: 0.02 mg IV or intraosseously (maximum single dose 0.5 mg or 1 mg in an adolescent ) repeat every 5 minutes. Respiratory symptoms may produce bronchitis or exacerbate underlying respiratory conditions. Give beta2 adrenergic agonists; inhaled ipratropium and systemic corticosteroids may be needed. Monitor vital signs. Hypotension may develop; give 0.9 NS, dopamine, norepinephrine.
    C) MANAGEMENT OF SEVERE TOXICITY
    1) Severe symptoms may include seizures, coma and respiratory arrest. Support airway and ventilate as necessary. Administer IV benzodiazepines, propofol, or barbiturates if seizures recur or persist.
    D) AIRWAY MANAGEMENT
    1) Usually unnecessary, but perform early if life-threatening cardiac toxicity (ie, conduction delays), coma, or significant CNS depression, or status epilepticus are present.
    E) ANTIDOTE
    1) None
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with symptoms limited to dermal or minor gastrointestinal effects can likely be management at home. GI symptoms typically resolve within 6 to 72 hours.
    2) OBSERVATION CRITERIA: Patients with neurological or exacerbation of underlying respiratory symptoms should likely be observed until symptoms resolve or clinical improvement with treatment.
    3) ADMISSION CRITERIA: Patients with evidence of cardiotoxicity, and/or seizures, or other persistent neurotoxicity (coma, agitation) should be admitted.
    0.4.3) INHALATION EXPOSURE
    A) Move patient to fresh air. Monitor respiratory function for respiratory tract irritation or bronchitis. Exposure may exacerbate underlying respiratory conditions (eg, asthma).
    0.4.4) EYE EXPOSURE
    A) Rinse eye with copious amounts of warm water. Ongoing symptoms may require further examination and treatment.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Remove contaminated clothing and wash exposed areas with soap and water. Persistent symptoms may require examination by a physician.

Range Of Toxicity

    A) Although no specific data exist on the amount necessary to cause human intoxication, eating a few contaminated shellfish may produce symptoms.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. The Centers for Disease Control and Prevention (CDC) has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdc.gov.
    b) ACUTE SYMPTOMS (WITHIN 48 HOURS)
    1) GI: Abdominal pain, cramping, nausea, vomiting, diarrhea. RESP: Conjunctival irritation, rhinorrhea, nonproductive cough, bronchoconstriction, exacerbation of underlying respiratory conditions (ie, asthma). NEURO: Confusion, paresthesias of face, throat and extremities, ataxia, distorted sensorium, vertigo. CV: Bradycardia. HEENT: Headache, salivation, ocular irritation and pupil dilation. DERM: Skin or nasal irritation, rash, dermatitis, hives, lacrimation and cough. SEVERE TOXICITY: Seizures, coma, or respiratory arrest may develop.
    c) CHRONIC SYMPTOMS
    1) Unknown.
    d) FATALITY RATE
    1) No human deaths reported.
    e) TIME TO ONSET OF SYMPTOMS
    1) INGESTION: Less than one hour up to 24 hours after eating contaminated seafood.
    2) AEROSOL: Immediate respiratory irritation.
    3) DERMAL: Immediate to delayed skin and mucous membrane irritation; symptoms most often within a few hours.
    f) DURATION
    1) INGESTION: Typically 6 to 72 hours.
    2) AEROSOL: Symptoms typically resolve once exposure is discontinued; however respiratory symptoms may persist days to weeks in individuals with underlying respiratory conditions.
    3) DERMAL: Unknown.
    g) CAUSATIVE ORGANISM
    1) The following organisms may produce illness: Karenia brevis (formerly Gymnodinium breve, formerly Ptychodiscus brevis), Karenia spp., Chatonella spp., Fibrocapsa japonica, and other marine microalgae that produce brevetoxins.
    h) TOXIN
    1) Brevetoxins: a suite of polyether toxins (CAS 98225-48-0).
    i) VECTOR
    1) Contaminated bivalve shellfish including: scallops, clams, mussels and oysters; contaminated water, aerosols, or foams/scum near the shore.
    j) ROUTE OF EXPOSURE
    1) Eating contaminated shellfish, inhaling contaminated sea aerosols, or direct skin/mucous membrane contact with contaminated seawater or sea foam/scum near the shore during a bloom.
    k) MECHANISM
    1) Sodium channel mediated depolarization resulting in a stimulatory nervous effect.
    l) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Gulf of Mexico, US Southeastern and mid-Atlantic coasts, New Zealand.
    m) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisoning, scombroid fish poisoning, pesticide poisoning including: organophosphate poisoning, cholinesterase inhibitor poisoning, microbial food poisoning and food allergies; inhalation of chemical respiratory irritants or skin contact of chemical/biological irritants (including possibly cyanobacteria).
    n) DIAGNOSIS
    1) Clinical presentation, history of shellfish consumption and meal remnant assay (mouse bioassay, ELISA, HPLC-MS/MS) or specimen assay (ELISA or HPLC-MS/MS).
    o) SUSPECT CASE
    1) INGESTION: Consumption of shellfish and onset of neurologic symptoms with or without GI symptoms within 30 minutes to 24 hours.
    2) AEROSOL: Exposure to ocean aerosols and immediate onset of new, or exacerbation of existing, respiratory symptoms.
    3) DERMAL: Exposure to ocean waters or aerosols and immediate onset of new, or exacerbation of existing, skin or mucous membrane symptoms.
    p) CONFIRMED CASE
    1) Suspect case and verification of brevetoxin in clinical specimen OR verification of brevetoxin in shellfish meal remnant OR confirmed bloom of Karenia brevis or other brevetoxin-producing organism in a relevant geographic area.
    q) ANIMAL SENTINEL DATA
    1) Seabird, manatee and dolphin fatalities have been reported.
    r) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)

Heent

    3.4.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Contact with contaminated water may produce mydriasis, irritation, lacrimation, rhinorrhea, and sneezing in humans.
    2) Salivation was reported in animals.
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) MYDRIASIS may be seen (Johnson et al, 1985).
    2) Eye irritation has been reported in people who swim in "red tides" (Ellis, 1985).
    3) MICE - LACRIMATION was reported in mice injected with brevetoxins T17 or T34 (Baden & Mende, 1982).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) RHINORRHEA may occur in persons exposed to aerosolized toxin (Hughes et al, 1977).
    2) SNEEZING may occur in persons exposed to aerosolized toxin (Pierce, 1986).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) MICE - SALIVATION was reported in mice injected with brevetoxins T17 or T34 (Baden & Mende, 1982).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Bradycardia has been noted in humans.
    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Bradycardia persisting for up to 12 hours has been reported in humans (McFarren et al, 1965), in dogs (Johnson et al, 1985), and in cats (p 355).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) BIPHASIC BLOOD PRESSURE RESPONSE
    a) Low doses administered to animals caused hypotension, while high doses (160 mcg/kg intravenous) caused hypertension (Borison et al, 1985).

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Coughing, sneezing, and difficulty in breathing has occurred in man and animals. Severely poisoned animals die of respiratory arrest.
    3.6.2) CLINICAL EFFECTS
    A) RHINITIS
    1) WITH POISONING/EXPOSURE
    a) Sneezing has been reported due to aerosolized brevetoxins created by wind action on red tide (Pierce, 1986).
    B) COUGH
    1) WITH POISONING/EXPOSURE
    a) Coughing has been reported due to aerosolized toxin created by wind action on red tide (Ellis, 1985). The respiratory irritant zone is generally within a few kilometers of the beach (Pierce, 1986).
    C) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) Brevetoxin B (PBTX) may precipitate asthma attacks in susceptible individuals or cause respiratory irritation in non-asthmatics. The toxin causes an activation of sodium channels which produces contraction as a result of acetylcholine release (Watanabe et al, 1988; Shimoda et al, 1988; Richards et al, 1990; Shimoda et al, 1987).
    b) In a study of 59 patients with asthma, exposure to aerosolized brevetoxins (walking along the beach for one hour during a red tide) was associated with significant increases in self reported symptoms of cough, wheezing, chest tightness, eye and throat irritation and small but significant decreases in FEV1 (forced expiratory volume in 1 second, mean decrease 38 mL +/-118 ml) and FEF25-75 (forced expiratory flow between 25% and 75%, mean decrease 95 mL/sec +/- 296 mL/sec) (Fleming et al, 2005). These differences were not seen when the subjects walked along the beach when there was no red tide.
    1) Similar results occurred among 97 patients with asthma who were exposed to aerosolized brevetoxins while walking along the beach during a red-tide. There were small, but statistically significant, decreases in FEV1 and the FEF25-75 (mean decreases of 36.4 +/-107.9 mL and 87.1 +/- 271.4 mL/sec, respectively) (Fleming et al, 2007).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOVENTILATION
    a) Labored breathing and death were reported in mice given brevetoxins T17 or T34 by ingestion or injection (Baden & Mende, 1982). Bradypnea was also seen in poisoned cats (Borison et al, 1985).
    b) Guinea pigs poisoned with brevetoxin have an initial increase in respiratory rate that is followed by respiratory depression (Franz & LeClaire, 1989).
    2) BRONCHOSPASM
    a) Although T34 toxin has some bronchoconstrictive effect, T17 appears to be the agent which causes the respiratory discomfort of coughing and sneezing during red tide episodes. This conclusion was based on animal studies (Baden & Mende, 1982).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Typical effects include paresthesias of the face, lips, and extremities, dystaxias, a feeling of confusion, and a distorted sensorium. More serious cases may develop seizures or coma.
    3.7.2) CLINICAL EFFECTS
    A) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) Distorted sensorium may occur. Warm fluids may taste cold or the skin may feel like "cold rain" (Johnson et al, 1985). Temperature reversal has also been reported (Morris et al, 1991).
    B) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures may occasionally develop after ingestion (Poli et al, 2000; Ellis, 1985).
    C) COMA
    1) WITH POISONING/EXPOSURE
    a) Coma has also been reported after ingestion (Poli et al, 2000; Borison et al, 1985).
    D) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) Paresthesias of the face, lips, and extremities may develop after ingestion (Poli et al, 2000; Ellis, 1985; Morris et al, 1991).
    b) The best documented and largest outbreak occurred in North Carolina in 1987 when a K. brevis bloom traveled up the eastern seaboard. Forty-eight cases were identified, and paresthesia was a prevalent symptom in 81% of cases (Watkins et al, 2008).
    E) ATAXIA
    1) WITH POISONING/EXPOSURE
    a) Weakness and/or difficulty with walking may develop after ingestion (Ellis, 1985; Morris et al, 1991).
    b) The best documented and largest outbreak occurred in North Carolina in 1987 when a K. brevis bloom traveled up the eastern seaboard. Forty-eight cases were identified, and ataxia was a prevalent symptom in 27% of cases (Watkins et al, 2008).
    F) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) Confusion or a feeling of drunkenness may be noted in humans (Johnson et al, 1985).
    G) TREMOR
    1) WITH POISONING/EXPOSURE
    a) Tremor and vertigo have been reported (Morris et al, 1991).
    b) The best documented and largest outbreak occurred in North Carolina in 1987 when a K. brevis bloom traveled up the eastern seaboard. Forty-eight cases were identified, and vertigo was a prevalent symptom in 61% of cases (Watkins et al, 2008).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CHOLINERGIC SYNDROME
    a) MICE - "Slud syndrome" (lacrimation, salivation, urination, and defecation) was observed in mice injected with brevetoxins T17 or T34 (Thampi et al, 1966).
    2) TREMOR
    a) MICE - T34 and T17 toxins produced tremors and muscle fasciculations (Baden & Mende, 1982).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Cramping, abdominal pain, and diarrhea may occur.
    3.8.2) CLINICAL EFFECTS
    A) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Ingestion of brevetoxins may cause nausea, vomiting, and intestinal cramping (Poli et al, 2000; Ellis, 1985; Morris et al, 1991).
    b) The best documented and largest outbreak occurred in North Carolina in 1987 when a K. brevis bloom traveled up the eastern seaboard. Forty-eight cases were identified, and abdominal pain was a prevalent symptom in 48% of cases. Nausea was reported in 44% of cases (Watkins et al, 2008).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea may be seen after ingestion of brevetoxins (Johnson et al, 1985; Morris et al, 1991).
    b) The best documented and largest outbreak occurred in North Carolina in 1987 when a K. brevis bloom traveled up the eastern seaboard. Forty-eight cases were identified, and diarrhea was a prevalent symptom in 33% of cases (Watkins et al, 2008).

Hematologic

    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEMOLYSIS
    a) A hemolytic agent has been associated with the red tide organism (Kim & Padilla, 1976). The Gymnodinium brevetoxins were found to have 1/6 the anticoagulant activity of carrageenan and 1/70 the activity of heparin (Doig & Martin, 1973). Hemolysis has not been reported in humans.

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Swimming in red tides may produce pruritus.
    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) WITH POISONING/EXPOSURE
    a) Itching and skin irritation has been reported in people who swim in red tides (Ellis, 1985).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory tests are useful in diagnosis of brevetoxin intoxication.
    B) Confirmatory testing (LC-MS) may be performed to measure brevetoxin metabolites in human urine if indicated. Bioassays, ELISA, HPLC-MS/MC) techniques have been used to detect brevetoxin in research and food (eg, meal remnants).

Methods

    A) CHROMATOGRAPHY
    1) THIN-LAYER CHROMATOGRAPHY has been used to isolate and purify brevetoxins (Baden et al, 1981).
    2) LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY (LC-MS/MS) has been used to identify brevetoxin metabolites from urine samples (Abraham et al, 2008).
    B) IMMUNOASSAY
    1) Baden et al (1988) also discuss a radioimmunoassay which is being investigated as a means to detect brevetoxins in foods. They found that while radioimmunoassay reflected structural similarities, a synaptosome assay (using rat brain synaptosomes) better reflected potency of each brevetoxin (Baden et al, 1988).
    2) Trainer & Baden (1991) have more recently described an enzyme linked immunoassay (ELISA) that can detect brevetoxin concentrations as low as 0.04 pM (Trainer & Baden, 1991) . ELISA has been used to isolate brevetoxins in shellfish and urine extracts (Abraham 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) ADMISSION CRITERIA: Patients with evidence of cardiotoxicity, and/or seizures, or other persistent neurotoxicity (coma, agitation) should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) HOME CRITERIA: Patients with symptoms limited to dermal or minor gastrointestinal effects can likely be management at home. GI symptoms typically resolve within 6 to 72 hours.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) OBSERVATION CRITERIA: Patients with neurological or exacerbation of underlying respiratory symptoms should likely be observed until symptoms resolve.

Monitoring

    A) No specific laboratory tests are useful in diagnosis of brevetoxin intoxication.
    B) Confirmatory testing (LC-MS) may be performed to measure brevetoxin metabolites in human urine if indicated. Bioassays, ELISA, HPLC-MS/MC) techniques have been used to detect brevetoxin in research and food (eg, meal remnants).

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/ NOT RECOMMENDED
    1) Emesis is not recommended due to potential seizures, coma, and respiratory arrest.
    B) ACTIVATED CHARCOAL
    1) Usually it is not known that food is contaminated until neurotoxic symptoms have occurred; gastrointestinal decontamination is unlikely to be useful once symptoms have developed. Brevetoxins are large, organic molecules which may be adsorbed to activated charcoal. Although no specific data exist, activated charcoal may be of some use soon after ingestion.
    2) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    3) 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).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) EMESIS IS CONTRAINDICATED due to potential seizures, coma, and respiratory arrest. Usually it is not known that food is contaminated until neurotoxic symptoms have occurred; gastrointestinal decontamination is unlikely to be of benefit once symptoms have developed.
    B) ACTIVATED CHARCOAL
    1) Brevetoxins are large, organic molecules which may be adsorbed onto activated charcoal. Although no specific data exist, activated charcoal may be of some use if administered soon after ingestion.
    2) 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.
    3) 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) ATROPINE
    1) In animal studies, 0.5 milligram/kilogram of atropine reversed the bronchoconstrictive effects of brevetoxin T17, as well as the rhinorrhea, lacrimation, salivation, urination, and defecation usually present (Baden & Mende, 1982).
    2) Atropine also reversed the bradycardic effects seen with brevetoxin administration in dogs, but did not alter the blood pressure effects (Johnson et al, 1985).
    3) No human studies are available.
    a) ATROPINE/DOSE
    1) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
    2) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.
    a) There is no minimum dose (de Caen et al, 2015).
    b) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).
    B) SEIZURE
    1) 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).
    2) 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 .
    3) 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).
    4) 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, 2010; Chin et al, 2008).
    5) 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).
    6) 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).
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) AIRWAY MANAGEMENT
    1) Usually unnecessary, but perform early if life-threatening cardiac toxicity (ie, conduction delays), coma, or significant CNS depression, or status epilepticus are present.

Inhalation Exposure

    6.7.2) TREATMENT
    A) SUPPORT
    1) Systemic symptoms are generally not seen with inhalation, and the symptoms of irritation are self-limited.
    B) BRONCHOSPASM
    1) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    2) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    3) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    4) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    5) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Although no specific data exist on the amount necessary to cause human intoxication, eating a few contaminated shellfish may produce symptoms.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) Human deaths attributed strictly to brevetoxins have not been reported (Ellis, 1985).
    2) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    2) Eating one meal of shellfish that have been contaminated with brevetoxins may cause neurotoxic effects. The exact amount of brevetoxin necessary to produce symptoms in humans has yet to be determined.

Pharmacology Toxicology

Toxicologic Mechanism

    A) There are several toxins isolated from Ptychodiscus brevis. T34 is lethal to fish and mice and inhibits cell culture systems. It causes respiratory arrest in fish and mice (Baden et al, 1981).
    B) Both T17 and T34 produce symptoms of muscarinic stimulation, such as increased salivation, runny nose, increased defecation, and urination in animals (Baden & Mende, 1982).
    C) T17 is thought to be the agent responsible for neurotoxic shellfish poisoning. T17 is more potent (in mice) than T34, regardless of the route of administration (Baden & Mende, 1982).
    D) T17 and T34 both cause complete block of neuromuscular transmission in animal models. T34 is more potent than T17 at neuromuscular blockade. Tissues used experimentally were able to recover from low concentrations of T17, but not from T34. Neuromuscular blockade does not appear to be due to acetylcholine depletion, but to persistent nerve depolarization (Baden et al, 1984).
    E) The principle mechanism of action appears to involve sodium channel mediated depolarization (Wu et al, 1985). Although the initial muscle contracture seen in muscle tissue experiments is inhibited by curare and tetrodotoxin and enhanced by acetylcholinestrase inhibitors and 4-aminopyridine. Baden et al (1984) concluded that neuromuscular block is NOT a result of neurotransmitter depletion.
    F) The brevetoxins are unlike saxitoxin in that they produce a stimulatory rather than a depressant nervous effect and that the brevetoxins block open the sodium channels in nerves while saxitoxin closes them (Wu et al, 1985; (Sheridan & Adler, 1989).
    G) Brevetoxins, in animal and human tissue studies, produced lower airway smooth muscle spasm by sodium channel stimulation in the cholinergic nerve fibers (Shimoda et al, 1987; Shimoda et al, 1988). They produce airway contraction and depolarization of airway smooth muscle (Richards et al, 1990).

Physicochemical

Physical Characteristics

    A) T34: crystalline solid (Baden et al, 1981)
    B) T17: fluffy white powder (Baden & Mende, 1982)
    C) STRUCTURE OF BREVETOXINS: These toxins are an eleven member hetrocyclic oxygen containing fused ring system ending with an unsaturated lactone on one end and an unsaturated aldehyde at the other (brevetoxin B). T17 is identical except that there is an alcohol group in place of the aldehyde found in brevetoxin B. There are several other similar toxins, including a chlorine containing analog (brevetoxin A) and 2 polycyclic ethers (Pierce, 1986).

Molecular Weight

    A) BREVETOXIN B: 894

References

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