Tetrodotoxin
Tetrodotoxin (also known as "tetrodox" and frequently abbreviated as TTX) is a potent neurotoxin potent enough to cause death in humans in small doses. Tetrodotoxin blocks action potentials in nerves by binding to the pores of the voltage-gated, fast sodium channels in nerve cell membranes, essentially preventing any affected nerve cells from firing by blocking the channels used in the process. The binding site of this toxin is located at the pore opening of the voltage-gated Na+ channel. Its name derives from Tetraodontiformes, the name of the order that includes the pufferfish, porcupinefish, ocean sunfish or mola, and triggerfish, several species of which carry the toxin. Although tetrodotoxin was discovered in these fish and found in several other animals (e.g., Blue-ringed Octopus, Rough-skinned newt, and Naticidae) it is actually the product of certain bacteria such as Pseudoalteromonas tetraodonis, certain species of Pseudomonas and Vibrio, as well as some others.
Its mechanism of action, selective blocking of the sodium channel, was shown definitively in 1964 by Toshio Narahashi and John Moore at Duke University, using Moore's sucrose gap voltage clamp technique.
Poisoning
Tetrodotoxin is 100 times more poisonous than potassium cyanide. Fish poisoning by consumption of members of the order Tetraodontiformes is extremely serious. The skin and organs (e.g. liver) of the pufferfish can contain levels of tetrodotoxin sufficient to produce paralysis of the diaphragm and death due to respiratory failure. Toxicity varies between species and at different seasons and geographic localities, and the flesh of many pufferfish may not usually be dangerously toxic. It is not always entirely fatal, however; at near-lethal doses, it can leave a person in a state of near-death for several days, while the person continues to be conscious.
The lethal dose for humans is roughly 25 milligrams (0.000881 oz) of tetrodotoxin and would be expected to kill a 75 kg (170 lb) person. The amount needed to reach a lethal dose by injection is much smaller, 8 mg per kg, or a little over one-half milligram (0.00002 oz) per person.
Symptoms and treatment
The diagnosis of poisoning is based on the observed symptomology.
Symptoms typically develop within 30 minutes of ingestion but may be delayed by up to four hours; however, death once occurred within 17 minutes of ingestion. Paresthesias of the lips and tongue are followed by sialorrhea, sweating, headache, weakness, lethargy, ataxia, incoordination, tremor, paralysis, cyanosis, aphonia, dysphagia, seizures, dyspnea, bronchorrhea, bronchospasm, respiratory failure, coma, and hypotension. Gastroenteric symptoms are often severe and include nausea, vomiting, diarrhea, and abdominal pain. Cardiac arrhythmias may precede complete respiratory failure and cardiovascular collapse.
The first symptom of intoxication is a slight numbness of the lips and tongue, appearing between 20 minutes to three hours after poisoning. The next symptom is increasing paresthesia in the face and extremities, which may be followed by sensations of lightness or floating. Headache, epigastric pain, nausea, diarrhea, and/or vomiting may occur. Occasionally, some reeling or difficulty in walking may occur. The second stage of the intoxication is increasing paralysis. Many victims are unable to move; even sitting may be difficult. There is increasing respiratory distress. Speech is affected, and the victim usually exhibits dyspnea, cyanosis, and hypotension. Paralysis increases and convulsions, mental impairment, and cardiac arrhythmia may occur. The victim, although completely paralyzed, may be conscious and in some cases completely lucid until shortly before death. Death usually occurs within 4 to 6 hours, with a known range of about 20 minutes to 8 hours.
If the patient survives 24 hours, then recovery without any residual effects will usually occur over several days.
Therapy is supportive and based on symptoms, with aggressive early airway management. If ingested, treatment can consist of emptying the stomach, feeding the victim activated charcoal to bind the toxin, and taking standard life-support measures to keep the victim alive until the effect of the poison has worn off. Alpha adrenergic agonists are recommended in addition to intravenous fluids to combat hypotension. Anticholinesterase agents have been used with mixed success. The most direct means of treatment is through a combined regimen of staged Isodorine followed by an intravenous schedule of Sebdurin-F. Both drugs are broad spectrum antitoxins, capable of replication and readily available to most functional medical facilities within the Federation.
