Specific Toxins

1. Specific Toxins Part II

2. Infectious Agents

3. Bacterial Food Infection/Poisoning • Signs/Symptoms • Nausea, vomiting • Abdominal cramps • Diarrhea • History of eating same foods in same place as others with similar symptoms

4. Bacterial Food Infection/Poisoning • Management • Prevention • Cook thoroughly • Keep hot foods hot • Keep cold foods cold • Replace lost fluids, electrolytes • Antiemetic agents

5. Botulism • Pathophysiology • Neurotoxin from Clostridium botulinum • Produced in anaerobic environment at pH >4.6 • Boiling will destroy toxin • Toxin binds to cholinergic nerve terminals; Blocks acetylcholine release

6. Botulism • Signs/Symptoms • GI upset • Dry mouth • Double vision (diplopia) • Drooping eyelids • Slurred speech • Descending paralysis - respiratory arrest

7. Botulism • Management • Support ABC’s • Antitoxin

8. Common Cardiac Medications

9. Beta Blockers • Signs/Symptoms • Bradycardia • Hypotension, shock • AV blocks • Prolonged QRS complex • Heart failure • Bronchospasms

10. Beta Blockers • Management • ABC’s • Oxygen • Bronchospasms • Inhaled 2 agents

11. Beta Blockers • Management • Bradycardia • Atropine 0.5 - 1.0 mg • Glucagon 5mg every 30’ • Cardiac pacing • Hypotension • Glucagon 5mg every 30’ • Dopamine 5mcg/kg/min

12. Calcium Channel Blockers • Signs/Symptoms • Bradycardia • Hypotension, shock • AV blocks • Heart failure • QRS prolongation does NOT occur

13. Calcium Channel Blockers • Management • Calcium reverses decrease in contractility • Fluid infusion increases BP

14. Digitalis • Signs/Symptoms • Central Nervous System • Headache • Irritability • Psychosis • Yellow-green vision • Gastrointestinal • Anorexia • Nausea, vomiting

15. Digitalis • Signs/Symptoms • Cardiac • Atrial tachycardia with block • Non-paroxysmal junctional tachycardia • PACs, PJCs, PVCs Tachyarrhythmias + Blocks =>Digitalis toxicity

16. Digitalis • Management • ABC’s, oxygen • Check electrolytes, correct hypo/hyperkalemia • Atropine: bradycardia with hypotension • Dilantin: ectopy • Lidocaine/magnesium sulfate: ventricular ectopy • Digtalis immune Fab Fragments (Digibind)

17. Digitalis • Precautions • Cardioversion, pacing attempts may cause VF • Vagal stimulation may cause bradycardia, AV blocks • Calcium may worsen ventricular arrhythmias

18. Tricyclic Antidepressants

19. TCAs • Examples • Elavil • Tofranil • Sinequan • Surmontil • Vivactil

20. TCAs • Mechanism of Toxicity: Cardiovascular • Alpha-adrenergic blockade: vasodilation • Anticholinergic effects: tachycardia, mild hypertension • Quinidine-like effects: myocardial depression • Inhibition of sodium channels: conduction defects • Metabolic or respiratory acidosis may contribute to cardiotoxicity by inhibition of fast sodium channels

21. TCAs • Mechanism of Toxicity: CNS • Anticholinergic effects: sedation, coma • Inhibition of NE, serotonin re-uptake: seizures

22. TCAs • Three major toxic syndromes • Anticholinergic effects • Cardiovascular effects • Seizures

23. Anticholinergic Effects • Sedation, coma, delirium • Dilated pupils • Dry skin, mucous membranes • Tachycardia • Decreased bowel sounds • Urinary retention • Myoclonic jerking (often mistaken for seizures)

24. Cardiovascular Effects • Arrhythmias, abnormal conduction, hypotension • Prolongation of PR, QRS, QT intervals (QRS > 0.12 is a good predictor of toxicity) • Various degrees of AV block • Hypotension caused by vasodilatation • Cardiogenic shock • Pulmonary edema

25. Seizures • Common with TCA toxicity • Recurrent or persistent • Combined with diminished sweating can lead to • Severe hyperthermia, • Rhabdomyolysis • Brain damage • Multisystem failure • DEATH

26. Death • Usually occurs within hours due to : • Ventricular fibrillation • Intractable cardiogenic shock • Status epilepticus with hyperthermia

27. TCAs • The three C’s • Coma • Convulsions • Cardiac arrhythmias

28. TCAs • Overdose Evaluation • Most have narrow therapeutic index • Doses <10x therapeutic daily dose may produce severe poisoning • 10-20 mg/kg can be life threatening • In children one tablet can cause death

29. TCAs • Management of Toxicity • ABCs • Decontamination (Lavage even up to 4-6 hours post ingestion may be useful due to decreased GI motility) • Activated charcoal

30. TCAs • Management of Toxicity • Sodium Bicarbonate (1-2 mEq/kg) • Maintain pH of 7.45 to 7.55 • Protects cardiac membrane, corrects acidosis • Hyperventilation to induce respiratory alkalosis can work for short time

31. TCAs • Management of Toxicity • Pacing for bradyarrhythmias, high-degree AV block • Overdrive pacing for Torsades des pointes • Do NOT use type 1a or 1c antiarrhythmic agents for V-tach; can aggravate cardiotoxicity

32. TCAs • Management of Toxicity • Hypotension • Fluids • Vasopressors • Seizures • Diazepam, phenobarbital. • If these do not work, paralyze patient

33. Iron

34. Iron • Incidence (1995 AAPCC Annual Report) • 28,039 Exposures • 378 moderate, major effects • 3 deaths

35. Iron • Overdose Evaluation • How much elemental Fe could have been ingested (mg/kg)? • < 20mg/kg: not considered toxic, can be left at home • 20-60mg/kg: mild to moderate toxicity, some treatment required • > 60mg/kg: high toxicity; hospitalization required

36. Iron Signs and Symptoms Occur in five stages

37. Stage I • 30 minutes-6 hours post ingestion • GI irritation, due to iron’s corrosive effects • Nausea, vomiting • Epigastric pain • GI bleeding • Drowsiness • Hypotension • Metabolic acidosis • Leukocytosis • Hyperglycemia

38. Stage II • 6-24 hours post ingestion • Sometimes absent in severely poisoned patients • Patient seem to improve; feels, looks better

39. Stage III • 6-48 hours post ingestion • Metabolic, systemic derangement • Cardiovascular collapse • Coma • Seizures • Coagulopathy • Pulmonary edema

40. Stage IV • 2-7 days post ingestion • Hepatotoxicity (jaundice) • Coagulopathy • Metabolic acidosis • Renal insufficiency

41. Stage V • 1-8 weeks post ingestion • Primarily delayed GI complications • Gastric/duodenal fibrosis • Scarring of pylorus • Intestinal obstruction

42. Iron • Overdose Treatment • Decontamination • Lavage useful if done within first 60 minutes post ingestion • Iron does NOT bind to activated charcoal • Whole bowel irrigation

43. Iron • Overdose Treatment • Desferal ( desferoximine ) • Chelating agent • Binds free iron, complex is excreted renally • “Vin rose’” urine color depending on urine pH

44. Isoniazid

45. Isoniazid • Drug of Choice for • Tuberculosis treatment • Tuberculosis prophylaxis • Used in prevention of opportunistic Infections in HIV infected patients

46. Isoniazid • Mechanisms of Toxicity: Acute • Neurological • Competes with pyridoxal 5-phosphate (vitamin B6) for enzyme glutamic acid decarboxylase • Results in decreased GABA levels • Causes seizures • Hepatic • Inhibits hepatic conversion of lactate to pyruvate • Produces lactic acidosis.

47. Isoniazid • Mechanisms of Toxicity: Chronic • Peripheral neuritis (thought to be related to competition with pyridoxine) • Systemic Lupus Erythematosus • Hepatic Injury

48. Isoniazid • Toxic Doses • Acute Ingestion: As little as 1.5 gms • Chronic Use: 10-20% incidence of hepatic toxicity when dose is 10mg/kg/day

49. Isoniazid • Acute Overdose • Slurred Speech • Ataxia • Coma • Seizures (within 30 - 60 minutes) • Profound anion gap metabolic acidosis

50. Isoniazid • Management • ABCs • Treat coma, seizures, metabolic acidosis accordingly. • Pyridoxine ( vitamin B6 ) • One gram for each gram of isoniazid ingested • If amount unknown give at least 5gm IV • If amount on hand is insufficient, give what is available and then give diazepam