Poisoning (intoxication)

1. Poisoning(intoxication) 1

2. Poisoning Outline of lecture: Definition Epidemiology Clinicalsymptoms Treatment – antidotes Typesofpoisoning: Chemicals Drugs Animal toxins Plant and bacterialtoxins 2

3. Poisoning Poisoning is a morbidity induced by the presence of venom (nox) in the organism. • acutepoisoning: resultsfromexposure (ingestion, inhalation, injection) ofaneffectiveamountofpoison (e.g. consumptionoftoadstools green, snakebite) • chronicpoisoning:resulting as a consequenceoflong-term incomeoflowdosesofcumulativepoison (eg. heavy metal poisoning). 3

4. Basic principles of toxicology The dose makes the poisioning (Paracelsus 1493-1541) LD50: lethal dosis 50% specifies the relative toxicity of substances The concentration of the substanceat which 50% of animalsdies within 24 hours after administration of the poison (approximate value depends on weight and condition of the individual). 4

5. Epidemiology • In the Czech Republic ~ 100-200000 intoxications per year (excluding recreational use of cannabis and ethanol). • Accidental (unintentional): usually children under 6 years • Attempted suicide (intentional self-harm) • Improper use or abuse of freely available medicaments (excessive dosing, combinations, expectations of euphoric effect ...) • Mortality: • <1% of all intoxicated individuals • 1-2% of suicide attempts 5

6. Clinical symptoms Non-specific symptoms of acute poisoning: • ➢ Gastrointestinal discomfort, vomiting, abdominal pain, diarrhea ➢ Headache ➢ Respiratory disorders • ➢ Sweating, salivation • ➢ Convulsions ➢ Cardiac arrhythmias ➢ Loss of consciousness ➢ Hallucinations (LSD = lysergic acid diamid, Psilocybin, MDMA aka Ecstasis, Cannabis...) ➢ Mydriasis / Miosis 6

7. Clinical symptoms The pacient may be: Agitated/ Excited: • Increased heart rate, blood pressure, respiratory rate, temperature and neuromuscular activity (e.g. cocaine, selective beta-agonists, hallucinogens, but also withdrawal symptoms) Inhibited: Decreased heart rate, blood pressure, respiratory rate, temperature and neuromuscular activity (e.g. sympatholytic, opiates, cholinergic agents – stimulants of muscarinic and nicotinic receptors, sedatives, hypnotics) 7

8. Clinical signs of poisoning Discordant: • simultaneous occurrence of stimulation and inhibition of physiological functions, or a gradual transition from one state to another • e.g. substances causing hypoxia/ asphyxia (CO, carbon monoxide), substances causing metabolic acidosis (methanol, ethylene glycol, salicylates) substances leading to liver failure, kidney failure or respiratory disorders Normal: • substances that are slowly absorbed, distributed, and metabolically activated or affect metabolic processes (e.g. paracetamol, cumulative poisons), poisoning as by "toxic time bomb" 8

9. Diagnosis • Recognition of the poisoning • Identification ofinducing substances (analysisofurine, blood, vomit...) • Determination of clinical impact and appropriate management 9

10. Treatment • Support of vital functions (O2, intravenous fluids) • Preventing further absorption of the poison (decontamination) • Support of elimination of the poison from the body • Administration of the antidotes 10

11. 2 phases of poisoning: 1. PRERESORPTIVE– inactivation and removalofunabsorbedtoxicsubstace. E.g. vomiting, flushingofstomach, washingthethe skin... 2. POSTRESORPTIVE(managingofconsequencesofpoisoning) a) inactavationoftoxic substance: antidotes b) blockingofsubsatncetoxiceffects 11

12. Types of intoxication Foreign substance = xenobiotic Poison = noxa • Chemicals – alcohols, heavy metals, anions, pesticidesand other industrial chemicals • Pharmaceuticals • Addictive substances (drugs) • Animal and plant poisons 12

13. Most frequent intoxications • Paracetamol (Acetaminophen) • the most common intoxication requiring • hospitalization. • CO(carbon monoxide) • the most common lethal intoxication/ death usually occurs prior to the hospitalization. • 1st place among accidental poisoning in Europe. • in the Czech Republic CO poisoning causes 140-150 deaths per year. 13

14. Paracetamol • Characterization: Paracetamol • (Acetaminophen, N-acetyl-p-aminofenol) • component of analgetics, antipyretics • (COLDREX, KORYLAN, PANADOL…) • the therapeutic dose for adults – from 325 to 650 mg/1 dose, • max. 4g/day. • - the therapeutic plasma level from 5-20 mg/ml. • - after oral administration the dose is absorbed within 0,5 to 1 hour. • - maximum plasma concentration is reached within 1 hour after administration • - passes well tissue including the placenta, overdose threatens the fetus Toxic dose: 100 mg/kg; adults: 7,5 g 14

15. Paracetamol Symptoms of acute poisoning: • Within few hours (0,5 - 24) after the overdose: nausea,loss of apettite, vomiting, sweating and drowsiness. • In extreme doses of 75-100 g for an adult may lead to coma and metabolic acidosis as early as 3-4 hours after ingestion. • After 3-4 days: increase in aminotransferases ALT, AST • After 5 and more days: liver and kidney failure, metabolic acidosis, myocardial injury, neurological symptoms and hematlogical disorders (trombocytopenia). 15

16. Paracetamol Mechanism: • Paracetamol is hepatotoxic, toxicity increases in combination with alcohol. • Paracetamol is metabolized in the liver by cytochrome P450 enzyme into the highly reactive metabolite N-acetyl-p- benzochinonimin (NAPQI), which is inactivated under physiological condition by conjugation with glutathioneand excreted by the kidneys as cysteine. • In overdose – fast depletion of available glutathione(decrease supplies under 30 %)- NAPQI metabolite attacks covalently cellular proteins in hepatocytes and causes their apoptosis. 16

17. Paracetamol First Aid: -Gastric lavage, vomiting, immediate administration of charcoal (50-100g) which binds well paracetamol. -Antidote is N-acetylcysteine -supplements glutathione reserves in the liver and renal tubular cell and thereby ensures inactivation of toxic metabolite NAPQI. -Administration of antidote up to 10 hrs after ingestion almost completely prevents fatal liver damage. 17

18. Carbon monoxide (CO) Characterization -Carbon monoxide is colorless and odorless, arises from incomplete combustion. -CO is part of each flue gas. -Exhaust gases gasoline or diesel engines contain a high percentage of CO. - CO in the atmosphere is normally present at a concentration of less 0,001% (or 10 ppm) -the most common cause of death for reasons of intoxication (death usually occurs prior to admission). -in the Czech Republic die for CO poisoning 140-150 pers./year (LD50): the concentration in air of 0.05% is already dangerous 18

19. Carbon monoxide (CO) Symptoms: - facial flushing, headache, vomiting, dizziness, visual disturbances, rapid breathing and heartbeat disturbances and loss of consciousness. 19

20. Carbon monoxide (CO)

21. Carbon monoxide (CO) • Mechanism: • CO binds to hemoglobin formingkarbonylhemoglobin (karboxyhemoglobin, COHb). • Affinityof CO to hemoglobin is200–300xgreaterthantheafinittyof oxygen. CO bindswiththesameaffinity to muscle myoglobin and heart myoglobin. • PhysiologicalconcentrationofCOHbis1-2%,forheavysmokers up to 10%). • COblocksthebindingsitesof hemoglobin for oxygen and causestissuehypoxia. • Physiologically CO as well as NO and SH2acts as a neurotransmiter (vasodilatoryeffect) and participate in theinflammatory response. 21

22. Carbon monoxide(CO) Mechanism II: • CO causes tissue hypoxia, tissue with high comsupntion of Oxygen (myocardium and brain) are the most affected. • CO blocks the activity of enzymes including P-450 and triggers metabolic acidosis. • Can cause neuronal apoptosis and consequently severe neurological disability leading to death. • CO is especially toxic to the fetus, which display a low partial pressure of Oxygen 22

23. Carbon monoxide (CO) • Firstaid: • Ensuringthesupplyoffresh air orartificialrespiration (due to highaffinityof CO to Hb has CO a long dissociation). • Medicalfirstaidinvolvestheadministrationof oxygen. • Hyperbaric oxygen therapy (HBO, applicationof 100% Oxygen underhighpressure). • HBOaccelerstesthedissociationofCOHb (from 90 to 20 min) and significantlyreducesthe risk ofischemia-reperfusioninjury. • In severe poisoningafterinitiationreoxygenation are developedreoxygenation, orischemia-reperfusioninjury (leads to execute a seriesofpathophysiologicalcascades, as activationneutrophiladhesion to endothelium and subsequentcapillarydamage, as well as theneuronalapoptosis). 23

24. Cyanidepotassium • Characterization: • Cyanide potassium (KCN): potassium salt of hydrocyanic acid. • White, crystalline, hygroscopic substance, lethal dose of 100–250 mg. • Reaction of KCN with atmosperic carbon dioxide forms extremely poisonous gas hydrogen cyanide (HCN), smelling of bitter almonds. • 2 KCN + CO2 + H2O (vzd.) → K2CO3 + 2 HCN • Potassium cyanide poison was used for executions during WW2 (cyklonB) or suicides of chieftains of the Nazi regime (Heinrich Himmler and Hermann Göring). • HCN may arise as a photodissociation product of the decay of nitroglycerin (angina pectoris). 24

25. Cyanidepotassium • Mechanism: • In the stomach the interaction of KCN with hydrochloric acid (HCl) releases highly poisonous hydrogen cyanide HCN. • Toxic effect: blocking the enzymes of respiratory chain in mitochondria. • The most important is the inhibition of cytochromeoxidase. - CN- binds to the ferric iron (Fe3+) contained in cytochromeoxidase thus blocking cellular respiration. Asa consequence the lactate concentration is increasing causing the metabolic acidosis, resulting in tissue suffocation, especially the brain centers. • Transport of oxygen in blood is maintained, because the iron in the hemoglobin is in the divalent form (Fe2 +). • Poisoning after ingestion of small amounts may take up to several hours. • When a large dose of hydrogen cyanide isreleased in the body (or when inhaled) death occurs in a few seconds. 25

26. Cyanidepotassium • First Aid: • After contact of KCN with skin, wash the affected area by water. • If swallowed, and the victim is conscious, induce vomiting immediately. • Antidotes: • i.v. administration of hydroxocobalamin (compound of B12) at high dose (~grams). The exchange of hydroxide group formsnon-toxic cyanocobalamin. • thiosulphate sodium - forms non-toxic thiocyanate (rhodanide),excreted in the urine. • Isoamylester of nitrous acid mediates binding of HCN to methemoglobin containing Fe3+ to form nontoxic kyanohemoglobin (HbCN). 26

27. Ethanol • Characteristic: ethyl alcohol, alcohol CH3CH2OH • Colorless hydrophilic liquids, lighter than water, former by fermentation of sugar by east (especially Saccharomyces genus) • It is easily absorbed (stomach, small intestine), and rapidly enters into the circulation. • The euphoric effects known from Middle Ages. • Metabolism: • ~10 % of the dose is excreted in the urine and breath • Most of the dose is metabolized in the liver by the enzyme • alcohol dehydrogenaseto produce highly toxic metabolite: • acetaldehyde - attacking S-S bridges of proteins – crosslinking cellular proteins, causing apoptosis of hepatocytes • final metabolites: acetate, CO2, H2O, fatty acids 27

28. Ethanol • Stages of intoxication: • The excitation stage • Increased mental and physical activity. Impaired coordination of movements with the extension of reaction time. • The narcotic stage • Vasodilatory effects, i.e. engorgement and redness of the skin, particularly on the face. Double vision and dizziness, especially when eyes are closed and lying. Increases blood pressure and pulse. Vomiting may occur and diuresis. After the previous euphoria started a major downturn, indifference and passivity accompanied by a loss of sense of reality. • The comatose stage • Started coma with complete motor weakening. Breathing is deep and slow (due to respiratory acidosis). When vomiting danger of aspiration of gastric contents and apnea. • Alcohol hypoglycemic coma • Ethanol inhibits gluconeogenesis from amino acids, lactic acid and glycerol • In liver. Hypoglycemia occur 4-12 hours after ingestion. 28

29. Ethanol • Physiological action: • toxic is particularly the metabolite acetaldehyde. • damage of hepatocytes, liver cirrhosis • damage to other organs, peripheral nerve disorders of brain activity • Treatment: • early vomiting. • gastric lavage. • hemodialysis. 29

30. Methanol • Characteristic: methyl alcohol, wood alcohol CH3OH • Colourless, alcoholic smelling liquid unlimitedly miscible with water. Volatile, flammable and highly toxic. • Solvent, an ingredient of antifreeze solutions, denaturant. • Mechanism: • The toxicity of methanol is based on the action of its metabolites. • Very slow metabolism, elimination about 7 times slower than ethanol. • Is metabolized in the liver by alcohol dehydrogenase forming the toxic formaldehyde. This is further converted by aldehyde dehydrogenase into the formic acid. The ultimate metabolite is carbon dioxide. • Peak levels of formic acid - about 2 days after ingestion. • Result: metabolic acidosis, impaired cell metabolism by formic acid and lactate. • disablement of CNS (similar to Parkinson symptoms), impaired vision, retinal disorders -light-sensitive nerve endings and the basal ganglia, where HCOOH accumulates. 30

31. Methanol • Symptoms : • Early symptoms: narcoticintoxication, drunkenness, drowsiness. • After 8 to 36 hours: headache, dizziness, comaorconvulsions. • First Aid: • Gastriclavage • As soon as possibleafteringestion – enzyme saturation by innfusionofethanol, (competitiveoxidationofethanol, 20xhigheraffinityforalcoholdehydrogenasethanmethanol), maintainingbloodethanollevelsofabout 1,5g/kg • Antidotealsofomepizole= 4-methylpyrazole, a specificinhibitor ofalcoholdehydrogenase. 15 mg/kg  after 12hours, leveldoesn`t has to bemonitored. • Long termhemodialysis (recommendedapproximately 5 days). • Regulationof plasma pH, natrium bicarbonateinfusion + folic acid, whichacceleratestheoxidationofformic acid. 31

32. Ethyleneglycol Characteristic:1,2-ethandiol • Viscousliquid, sweet taste, odorless and colorless. • Substance ofantifreezesolution in thecars (Fridex). • Symptomsofpoisoning: • CNS depression, euphoricintoxication, narcoticeffects as alcohol, later GI problems, thedevelopmentofacuterenalfailure • Toxicmetabolites are: glycolaldehyde, glyoxylate, oxalate • Metabolites cause acidosis, anuria, pulmonaryedema and brain, acuterenalfailure. 32

33. Ethyleneglycol • First Aid: • Gastric lavage • Blocking the formation of toxic metabolites – antidotes administration: ethanol • (per os, intravenous) maintain the level of 1-2 g/kg, fomepizole (15 mg/kg ). • Hemodialysis in severe poisoning • Correction of acidosis – Sodium bicarbonate infusion (NaHCO3). 33

34. Organophosphates • Characteristics: • Organophosphates are phosphoric acid esters. • The most widely used organic phosphorus compounds. • Series of essential biomolecules, including DNA and RNA and many cofactors, e.g. Adenosine triphosphaet (ATP), nucleotiesy (ATP, UTP, GTP, CTP and their deoxy derivatives) • Basis of - insecticides: (malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos) • - herbicides(tricresylphosphates) • - nerve paralysis weapons (soman, sarin, tabun • nebo VX). 34

35. Organophosphates • Mechanism: • nerve paralytic • Inhibitorsofacetylcholinesterase (AChE),whichcatalyzesthedegradationoftheneurotransmitteracetylcholineintocholine and acetate in thesynapticcleft. • Theresultisaccumulationof acetylcholine in thesynapticclefts and subsequentneuromuscularparalysis (sustainedcontractionofthemuscles) throughoutthe body. • Death by suffocation • Symptoms: • Salivation, lacrimation, urinaryurgency and defecation, motility ofthe digestive system, vomiting and downloadthepupils. May occurbronchospasm and bradycardia. • First Aid: • Antidote: atropine, blocksperipheralactionof acetylcholine 35

36. Heavy metals • Lead, mercury, copper, cadmium • Characterization: • The cumulative poisons, minimaly excreted and stored in the body, e.g. In fat, hair, bones, livers. • During the food chain leads to increasing concentrations in organisms. • Carcinogenic. • Lead: Plumbum Pb • Symptoms of poisoning: facial pallor, constipation, loss of appetite, colic, anemia, headache, convulsions, chronic nephritis, brain damage and disorders of the central brain system • - Disruption of porphyrin metabolism (ALAD, FCH – sideroblasts) • Treatment: consists in the formation of the complex and the masking Pb by strong chelating agent. • . 36

37. Heavy metals • Mercury: Hydrargyrum, Hg • The use of dental amalgamfillings. • Is stored primarily in the kidney and to a lesser extent in the liver and spleen. In the organism persists for decades. • Symptoms of chronic poisoning are often nonspecific: • hair loss, digestive disorders, neurological and psychiatric problems, anemia, chronic candidiasis treatment contrary, rheumatic disease, or kidney disease (glomerular). •When a single high dose of mercury always occur abdominal pain, diarrhea and vomiting. • Treatment: milk or white (insoluble precipitates Hg-albuminate), chelating agents (dimerkaptopropan sulfonate), hemodialysis 37

38. Animal poisons • Snakes 2.Amphibians • Insects • Coelenterates 4.Microorganisms 38

39. Animal poisons - snakes Poisonoussnakesinjectvenom by canals in teeth. Venomisformed in glandlocated on the oral floor. Glandevolvedfromthesalivaryglands and has externally and internallysecretoryfunction. • Venomcomposition:highlyviscous, stickyliquid, white to orangecolour. • Multicomponent.Themaintoxiccomponent are enzymes, aminoacids and peptides, whichacts as: -neurotoxines (pre a post synaptic) • -cardiotoxin • -vasoaktivní -cirkulační toxines • -hemolysiny • -componentaffectingcoagulation • Enzymes: • Hyaluronidase: cleaves ECM • Phospholipase: cleaves lipids. It works neurotoxic (bungarotoxin, taipotoxin, myotoxic or heamolytic. • Proteolytic enzymes: decomposition of the tissue protein, tissue damage and circulatory disturvances. They may affect the coagulation, e.g. Thrombin or anticoagulant activity. Hemorhaginy cause re-endothelializationof blood and lymphatic capillaries. Also cause the release of histamine and bradykinine (vasodilatation). 39

40. Animal poisons - snakes • European adder (Vipera berus) – the only venomous snake • of the Czech Republic. Forests, meadows, clearings and • stony and rocky terrain of the Central Europe to 1500m. -Aktive mostly in the daytime and at nightfall. -Poison contains mainly hemorhagine, circulating toxins and coagulation-active substances. Bite: Vipers regulate the amount of venom injected at defensive bites intoxication occurs in less than 50 % of cases. For an adult does not mean most serious threat. In the Czech Republic, dozens of bites/year. Symptoms:swelling (due to paralysis lymphatics vessels), greater response to pain lymph nodes, nausea, vomiting, sweating, elevated temperature. When possible allergic reaction, anaphylactic shock, circulation shock, contraction of smooth muscle in the gastrointestinal tract and bronchi due to histamine and subsequent asphyxia, colic, diarrhea. Symptoms generally persist for longer than 48 hours. First Aid:immobilization of the affected limb, sedatives, analgesics, rest, fluids Antidote: the specific recombinant antibody. 40

41. Animal poisons - snakes • Indian cobra(Naja naja): India, 1-2m, • The distinctive marking on the cephalothorax • Poison - synaptic neurotoxins that paralyze muscles thus affecting the respiratory and cardiac activity. • Bite symptoms manifest from 15 minutes to 2 hours and can be fatal in less than one hour. Black mamba (Dendroaspis polylepis) 2-4m, the most venomous snake in Africa. • Poison contains neurotoxins, paralysis, high death rate. • Immediate life support, antiserum most difficult to reach. 41

42. Animal poisons - snakes • Eastern diamondback rattlesnake (Crotalus adamanteus) Vipers, the most venomous snake and the largest in North America. Occurrence southeast USA. Poison: proteolytic enzymes Symptoms: Intense local reaction with severe hemorrhages to necrosis (leads to expose the long bones of the limbs). For the overall reaction is characterized by severe coagulopathy and hypovolemic shock. Coastal taipan (Oxyuranus scutellatus). The family of the coral Up to 3 meters, are among the most venomous snakes of the world. Occurance: coast of Australia and Papua-New Guinea -Mortality bite approaching 90%. -the Antiserum, early application provides a high chance of rescue. 42

43. Animal poisons - frogs • Kokoe poison frog (Phyllobatesaurotaenia)South American frog – skin glands contain steroidal alkaloid batrachotoxin. • The secretion is used as a South American Indians curare. • Venom is excreted in colorless glands located at the back. • Frogs don`t synthesize thevenom, but they ingest in the food. • Batrachotoxin: selectively activates the Na+ion channel without reciprocal changes K and Ca ions, which leads to depolarization of neuronal membranes and subsequent paralysis. • One of the most toxic poisons: lethal dose of less than 200 pg. ~ 15x more potent than curare. • Neurotoxic (CNS and periphery) cardiotoxic (arrhythmia to • cardiac arrest). There is no antidote • Used by the Indians of western Colombia for hunting (used to produce poisoned arrows into blowpipes). • Common toad (Bufobufo): skin glands contain the steroids bufotoxin and bufogenine. Influence of ion transport in the cardiac muscle. Arrhythmias, dizziness. Due to the low concentration of neurotoxins - minimaldanger. 43

44. Insect • Hymenoptera • Spiders • Scorpions Hymenoptera Bees, wasps, hornets, ants Sting contains: • Biogenic amines: histamine, serotonin, acetylcholine • peptides: melitin to 50% by volume (disruption of membrane mast cell, degranulation), kinin (vasodilation, muscle contraction) enzymes: hyaluronidase, phospholipase A (ECM cleavage, disruption of membranes, allow the penetration of tissues other components poison. The fundamental problem that causes an allergic reaction, anaphylactic shock, apnea. Treatments: Desinfection injection, antihistamines, glucocorticoids 44

45. Insect - spiders (Arachnida) Black widow (Latrodectus mactans) the most common venomous representative of the American continent also occurs in southern Europe, for example Croatia. • Poison: a-latrotoxin(neurotoxin, affects neuromuscular endings) further protease, hyaluronidase, phosphodiesterase. • Symptoms: edema, erythromycin, pain, tremor, dyspnoe. The bite is not fatal, there is an effective antidote. 45

46. Insect - spiders (Arachnida) Funnel-web spider (Atrax robustus) - Astralian funnel-web spider, one of the largest in the world, it occurs primarily in New South Wells (Sydney). Poison:robustoxin - neurotoxin acts on presynaptic terminals, atrotoxin, acts on neuromuscular terminals and releasing neurotransmitters, hyaluronidase. Symptoms: spasms of whole muscle groups in the upper half of the body, abdominal cramps bites to lower limbs. Irritation of the parasympathetic nervous systém, increased secretion of glands: sweating, tearind and overproduction of mucus in the airways. 46

47. Coelenterates • Octopus • Corals • Anemones Poison of coelenterates form mostly proteolytic enzymes, low molecular weight peptidesand glycoproteins - e.g. congestin, thalassin, eginatoxin. Cnidocysts (nematocysts) - unicellular poison glands, covering tentacles and sometimes all over the body • Inside is the spiral fiber with a thin tip that coelenterates shoot into the body of animals. Fiber and tip are dipped into poison. • After touching the local reaction occurs (stinging, erythema to vesicles), tissue necrosis. • On the mucous membranes and corneal can occur ulceration, which is only slowly healing. When massive intoxication - the overall reaction with nausea and vomiting, muscle cramps, breathing disorders, kidney damage, heart failure. 47

48. Jellyfish Sea wasp (Chironex fleckeri) • Deadly species of sea jellyfish from the family of Chirodropidae • Lives in coastal waters of Australia. • Head approximetaly 25 cm in diamater. • Up to 3 meters long, thin sticky tentacles covered by number of stinging cells. • Stinging cells in contact with the human skin causes severe pain followed by swelling and often shock, causing heart failure leading to drowning swimmer Portuguese man o' war (Physalia physalis) Atlantic shore of Portugal and Spain. Accidentaly passes gibraltar in to the Mediterranean Sea. 48

49. Octopus Blue-ringed octopus and Greater blue-ringed octopus( species of Hapalochlaena ) • They occur in shallow waters from northern Australia to Japan. • Size to 20cm Poison is consists of tetrodotoxin(TTX) – a neurotoxin, blocks the fast Na+ channels during depolarization, is among the strongest animal poisons. • hurt and intoxication beak. Symptoms: numbness of the tongue, blurred vision, subsequent blindness. Poison paralyses the muscles. Systemic paralysis occurs within three minutes, including respiration. Cyanosis, choking. • Octopuses have two venom glands (comparable in size with the brain), and each has a different composition toxins. First gland produces a toxin which stuns prey, which then feeds. Poison from the second gland is used as a defense. • There is still no antidote ! 49

50. Octopus Blue-ringed octopus and Greater blue-ringed octopus(species of Hapalochlaena ) • First Aid: is necessary immediate and long-term support of vital functions, artificial respiration and heart massage. If the patient is treated, the poison is eliminated from the body upon 24 hours without sequelae. 50