Animal and plant toxins

1. Animal and plant toxins

2. Animal toxins are produced by a variety of animals for the purpose of: 1- Defense 2- Obtaining prey 3- Metabolic byproduct (poisons)

3. Venomous Poisonous Toxic Animals • Produce toxin in a specialized secretory gland • Venom is a toxic substance injected through a bite, sting or spit • e.g. snakes, scorpions, jellyfish, bees and wasps • Some who have deadly bacteria in his mouth • Biting causes bacterial contamination of the wound that may spread • e.g. Komodo dragon • Produce toxin in various tissues • The poison is ingested or absorbed through the skin • e.g. some amphibians, fish or insect

4. I-Venomous animals 1- Snakes Snake venom is highly modified saliva that is produced by special glands of certain species of snakes It is injected through biting or absorbed through cuts or scratches through spitting

6. Snake venom is a mixture of proteins some with enzymatic activity: 1- Phosphodiesterases→ interfere with the prey's cardiac system → lowering theblood pressure. 2- ATPases→ breaking down ATP → disrupt the prey's energy fuel use. 3-Phospholipase A2 causes hemolysis by lysing the phospholipidcell membranes of RBCs.

7. There are three distinct types of snake venom: • Hemotoxicvenomsaffect blood coagulation (act on the heart & CVS). • Neurotoxicvenoms acts on the nervous system and brain. • Cytotoxicvenomshas a localized action at the site of the bite.

8. Neurotoxins • Fasciculins: • Dendrotoxins: • α-neurotoxins:

9. The beginning of a new impulse: • A) An exchange of ions across the nerve cell membrane sends a depolarising current towards the end of the nerve cell. • B) When the depolarising current arrives at the nerve cell terminus, the neurotransmitter Ach is released into synapse. It moves across the synapse to the postsynaptic receptors. • C) If ACh remains at the receptor, the nerve stays stimulated, causing incontrollable muscle contractions. This condition is called tetany. An enzyme called acetylcholinesterase destroys the ACh so tetany does not occur.

10. neurotransmitter Synaptic vesicle Reuptake pump Voltage gated ca channel Receptor

11. Fasciculins: • These toxins attack cholinergic neurons by destroying acetylcholinesterase (AChE). ACh therefore cannot be broken down and stays in the receptor. This causes tetany, which can lead to death. • The toxins have been called fasciculins since after injection into mice, they cause severe, generalized and long-lasting (5-7 h) fasciculations. • Snake example: found mostly in venom of Mambas and some rattlesnakes

12. Neurotoxins: • These toxins attack cholinergic neurons by destroying AChE. Ach is not broken down & stays in the receptor, Causing tetany & death. • Dendrotoxinsinhibit neurotransmissionsby blocking the exchange of ions across the neuronal membrane ==> no nerve impulse,paralysis. • α-neurotoxins attack cholinergic neurons. They mimic the shape of the Ach and therefore fit into the receptors→ they block the ACh flow → feeling of numbness and paralysis.

13. Cytotoxins • Phospholipases: An enzyme transforming the phospholipid molecule into a lysophospholipid (soap) ==> rips a hole in the cell membrane. Consequently water flows into the cell and destroys the molecules in it. That is called necrosis.

14. Cardiotoxins: Muscle venoms. They bind to particular sites on the surface of muscle cells causing depolarisation ==> preventing muscle contraction. On the heart muscle: the heart will beat irregularly and stop beating, which will cause death. • Haemotoxins: The toxin destroys red blood cells (haemolysis). As it is a very slowly progressing venom it would probably not kill a human - another toxin in the snake’s venom would most certainly have caused death by then.

15. Local Toxicity: Local tissue necrosis due to direct enzymatic action → pain, swelling, edema and discoloration of the site of bite. Cardiovascular Toxicity: Initial tachycardia, and mild hypertension followed by hypotension or cardiovascular shock.

16. Hematologic toxicity: • Some venoms have anticoagulant effect and interfere with the action of clotting factors → → Serious hemorrhage. • In addition to thrombocytopenia. • Hemorrhage may be due to: • Increase in fibrinolytic activities of plasminogen • Direct effect on phospholipids of red cell membranes

17. Bite victims may show bleeding from nose or gums, the bite site & in saliva, urine & stools.

18. Neurologic Toxicity: Many types produce neurotoxicity through: • Direct binding to postsynaptic Ach receptors causing neuromuscular weakness and paralysis. • Inhibitingcholinesterase→↑ Ach→the prey lose muscle control

19. Neurotoxins produce neuromuscular paralysisranging from ophthalmoplegia, flaccid facial muscle paralysis & inability to swallow to larger muscle paralysis & finally to paralysis of respiratory muscles & asphyxiation.

20. Renal toxicity: Acute renal failure either due to: • direct effect of the venom • complication of anticoagulant effect or cardiovascular shock.

22. Management of toxicity: 1- First aid: • Wash the bite. • Immobilize the bitten area & keep it lower than the heart. • A bandage is wrapped above the bite, not cutting blood flow. • Get medical help. 2- In hospital: • Endotracheal intubation in case of respiratory failure. • Saline & vasopressor in case of hypotension • Blood component therapy (plasma or packed RBCs) • Anticholinesterase as neostigmine to treat paralysis

23. Antidote Correct identification of the offending snake is important, the dead snake should be brought with the patient There is nearly an antivenom for most venoms.

24. 2- Scorpions Scorpion venom is neurotoxic in nature however hemiscorpiusleptutrus iscytotoxic. Scorpion venom causes local and systemic effects.

25. Mechanism of neurotoxicity: • Venom contains a neurotoxic protein, which activates Na-channels →increase Na influx →continuous depolarization (causing sudden release of catecholamines) & repetitive contraction of muscle fibers → paralysis. • Both sympathetic and parasympathetic neurons are stimulated → autonomic storm.

26. Local effect: Local pain, numbness at site of sting • Systemic effect: • Initial Parasympathetic stimulation; vomiting, sweating, increase in pulmonary secretions, bradycardia, and hypotension (hypovolemia, peripheral cholinergic & central vagal stimulation). • Pulmonary edema (severe impairment in left ventricular systemic function). • Peripheral vasoconstriction and dilated pupil secondary to sympathetic stimulation (long lasting).

27. In children jerking of the extremities mistaken for seizures • Death may occur due to ventricular arrhythmias, pulmonary edema or several allergic reaction. • Management of toxicity: 1- First aid: Immobilize bitten part Apply cold packs over the site of sting

28. In hospital: • Local severe pain relieved by local anaesthetic (xylocaine) and administration of NSAIDs. • Fluid replacement (electrolyte imbalance & hypotension) • Sedation with BZs to control anxiety • Tracheal intubation & hyperventillation (pulmonary edema) Antidote: • Scorpion venom is poor antigen thus it is difficult to prepare a potent antivenin. • Prazosin (α- blocker) counter act venom systemic effects.

29. 3- Jellyfish: • Stinging cells (nematocysts) penetrate the dermis & inject venom. • Symptoms range from: cutaneous rash to cardiovascular & respiratory collapse.

30. Mechanism of toxicity: • Act by causing abnormalities in Na & Ca, disrupting cellular membrane, releasing inflammatory mediators & direct toxic effects.

31. Symptoms: Immediate local effects: Pain, erythema, linear purple red marks (tentacle prints) & pruritic lesions. Systemic effects: Neurologic (agitation & confusion) due to severe pain & hypoxia. For box jellyfish: cardiovascular collapse, bronchospasm, pulmonary edema & respiratory failure due to respiratory muscle spasm & paralysis Death due to cardiovascular collapse, neuromuscular paralysis & respiratory failure.

32. Management: 1- first aid: • Apply vinegar (acetic acid inactivate stinging cells before they release their venom) • Remove any adherent tentacles. • CPR in case of cardiac arrest 2- In hospital: • Pain: apply ice, analgesic & antihistamines • narcotic analgesic in severe pain • Fluid infusion, Tredelenburg position & vasopressors in case of hypotension • Hyperventilation • Box jellyfish antivenin should be given within minutes

33. 4- Bees and wasps: Their sting may result in symptoms ranging from minor local pain and swelling to life threatening respiratory and cardiovascular effects.

34. Bee stings typically produce immediate, sharp or burning pain, slight local erythema & edema followed by itching. • It’s said that 50 stings can lead to respiratory dysfunction, intravascular hemolysis, hypertension, myocardial damage, hepatic changes, shock & renal failure. • With 100 or more stings, death can occur.

35. In allergic individuals (previously stung) severe allergic Rx may occur. In extreme cases anaphylactic shock due to IgE mediated system allergic response may result in death. Antidote: Adrenaline is the drug of choice for systemic sting Rx

37. Plant produce toxins as defense mechanism 1- Anticholinergic plants: Plants containing alkaloids as: atropine, hyoscyamine, hyoscine and scopolamine • The most common plants containing anticholinergic alkaloids are:Atropa belladonna & Datura species

38. They are all M-blockers → Anticholinergic syndrome: Mydriasis, tachycardia, Urinary retention, Increased intraocular pressure; dangerous for people with glaucoma. In CNS; Delirium, confusion, Disorientation & agitation.

39. Antidote: Acute anticholinergic syndrome is completely reversible and subsides once all of the toxin has been excreted. Previously, reversible cholinergic agents such as physostigmine were used. The current recommended treatment is symptomatic and supportive management.

40. 2- Cardiac glycosides plants: Plants that produce toxicity similar to digoxin In the heart they inhibit Na + /K + pump and increase Ca2+ available for contraction of the heart muscle and improves contractility.

41. Digoxin also increases vagal activity via its action on the CNS, thus decreasing the conduction of electrical impulses through the AV node. CV signs appears as toxicity increases, cardiac conductance abnormalities, bradycardia, AV block and hypotension.

42. Hypokalemia is common with acute overdose CNS effects; include, headache, drowsiness, hallucinations and confusion in severe cases.

43. Antidote: Digoxin Immune Fabis the generic name for an antidote for overdose of digitalis It is made from immunoglobin fragments from sheep who have already been immunized with a digoxin derivative. It is administered by iv injection in emergency cases.

44. 3- Cyanogenic Glycoside plants These are plants that release CN during digestion or during cooking. An example of these is amygdalin from almonds. Cyanogenic glycosides can be found in the fruits including cherries, apples, plums, almonds, peaches, apricots, and raspberries.

45. The cyanide anion is an inhibitor of the enzyme cytochrome c oxidase. It attaches to the ferric ion within this protein. As a result, the electron transport chain is disrupted, meaning that the cell can no longer aerobically produce ATP for energy.

46. The effects of cyanide ingestion are very similar to the effects of suffocation because cyanide stops the cells of the body from being able to use oxygen.

47. Tachypnea and hyperpnea followed by respiratory depression and severe apnea. Cardiovascular collapse with bradycardia and hypotension Headache, agitation, tremor and coma may occur.

48. Antidote: • Serious clinical effects treat with sodium nitrite, iv injection. Nitrites + Hb → oxidationFe2+ → Fe3+ thus converting Hb → met Hb. CN- binds to metHb rather than cytochrome oxidase enzyme Met Hb → cyano metHb

49. In the last step, the intravenous sodium thiosulfate converts the cyanomethemoglobin tothiocyanate,sulfite, and hemoglobin & The thiocyanate is excreted. CyanometHb + Na2S2O3 → metHb + NaSCN

50. Another antidote: Hydroxycobalaminreacts with cyanide to formcyanocobalamin. Cyanocobalamin can be eliminated by the kidneys. This method has the advantage of avoiding the formation of methemoglobin.