SUBSTANCES THAT CAN KILL A TODDLER WITH ONE TABLET OR TEASPOON

1. SUBSTANCES THAT CAN KILL A TODDLER WITH ONE TABLET OR TEASPOON

2. Overview • Most substances ingested by a child in a small amount are harmless. • Few substances that are ingested in a small amount can be deadly to a child.

3. Most Toxic Pediatric Ingestions • Ethylene Glycol (Antifreeze) • Methanol (Windshield washer fluid) • Clonidine • Imidazoline decongestants (Visine) • Calcium Channel Antagonists (Verapamil) • Beta Blockers (Toprol)

4. Most Toxic Pediatric Ingestions • Sulfonylureas (Glyburide) • Camphor (Campho-Phenique) • Theophylline • Lomotil (Diphenoxylate)

5. Ethylene Glycol • Toxic alcohol found in antifreeze • Sweet to the taste, appealing green color • Relatively easy for child to access

6. Ethylene Glycol Range of Toxicity • As little as a teaspoon can be toxic in a toddler. • Child may drink small amount from a radiator or from radiator drainage. • Often found out of original container in garages

7. Ethylene Glycol Clinical Presentation • Initially child will appear inebriated and may act drowsy. • Ethylene Glycol itself is not toxic, its metabolites are toxic.

8. Ethylene Glycol NAD+ Lactic Acid Alcohol Dehydrogenase X Pyruvate NADH Glycoaldehyde Krebs Cycle Aldehyde Dehydrogenase Fomepizole Glycolic Acid Glycolic Acid Oxidase -Hydroxy--ketoadipic Acid Glyoxylic Acid Formic Acid Hippuric Acid Calcium Oxalate Crystals Oxalic Acid + Calcium

9. Ethylene Glycol Treatment • Start iv fluids if possible and transport to nearest facility that can provide adequate care. • If large ingestion child may need transfer to tertiary facility that can provide hemodialysis

10. Methanol • Methanol is major component found in windshield washer fluid. • As little as mouthful may be toxic in a toddler.

11. Methanol • Methanol is also toxic alcohol • Like EG, it is the metabolites that are toxic.

12. Fomepizole Lactic Acid Methanol NAD+ Alcohol Dehydrogenase X Pyruvate NADH Krebs Cycle Formaldehyde Aldehyde Dehydrogenase pH Formic Acid Formate dependent Folate Dependent Detoxification Folate / Leucovorin CO2 + H2O

13. Methanol Clinical Presentation • Initially child may have no noticeable symptoms, may appear normal. • May have long latent period as MEOH is converted to formic acid. • Can be dangerous as child appears normal and parents may be reluctant to transport. • If not treated after formic acid is formed will cause severe acidosis and death.

14. Methanol Treatment • Is bound by activated charcoal - again small molecule - will get minimal absorption • Start intravenous fluids if possible and transport to closest facility that can provide adequate care. • Child may need transfer to tertiary facility for possible hemodialysis.

15. Clonidine • Clonidine is medication used to relieve hypertension. • Sometimes used in children to treat ADHD (new treatment).

16. Clonidine • Clonidine can cause hypotension and severe drowsiness. • Has long half life, child may appear asymptomatic for several hours or may present with sever drowsiness.

17. Clonidine • Readily bound by activated charcoal • Narcan has been shown to reverse drowsiness – must be given in large doses, start with 5 mg and repeat if not effective. • Narcan effective in some case and not others, reason is not known.

18. Clonidine Treatment • Give activated charcoal (without sorbitol) if available. • Start intravenous fluids and give narcan, transport to nearest facility that can provide adequate care.

19. Imidazoline Decongestants • Imidazaoline decongestants found in many eye preparations and nasal preparations • Visine • Afrin

20. Imidazoline Decongestants • These drugs have structure and effects very similar to Clonidine. • Imidazolines have presynaptic alpha-2 stimulant effects just like clonidine. • Treatment will be similar

21. IMIDAZOLINE DECONGESTANTS Range of Toxicity As little as 7.5 ml of tetrahydrozoline has caused sedation in children. Deaths have been reported from IV administration but not from ingestion.

22. IMIDAZOLINE DECONGESTANTS Treatment Establish IV access Activated Charcoal per local protocol Contact Poison Control Supportive Care Transport

23. CALCIUM CHANNEL ANTAGONISTS Widely used medications to treat angina, hypertension, supraventricular tachycardia, and migraines Examples: Diltiazem (Cardiazem) Nifedipine (Procardia)

24. Calcium Channel Antagonists Mechanism of Toxicity • Slow influx of calcium through cellular calcium channels • Results in coronary and peripheral vasodilatation • Slowed AV nodal conduction and depressed sinus node activity.

25. Calcium Channel Antagonist Clinical Effects • Hypotension • Bradycardia • Nausea/Vomiting • Stupor/Confusion

26. Calcium Channel Antagonist Range of Toxicity NO AMOUNT IN A CHILD IS SAFE TO OBSERVE AT HOME.

27. Calcium Channel Antagonist Treatment • Administer activated charcoal without cathartic if available - per local protocol • Establish IV Access • Contact Poison Control • Transport to Nearest ED - Child will need admission

28. BETA BLOCKING AGENTS Agents are widely used for treatment of hypertension, angina, arrhythmias, and migraines. Names Generally end in -olol Examples: Atenolol (Tenormin, Toprol) Labetalol (Normodine)

29. BETA BLOCKING AGENTS Mechanism of Toxicity • Blockade of beta-adrenergic receptors - specificity seen in therapeutic use is lost in overdose amounts • Propranolol and other similar agents will further decrease myocardial contractility • Sotalol - has type III antiarrhythmic activity and may produce torsades

30. BETA BLOCKING AGENTS Clinical Presentation • Hypotension • Bradycardia • CNS Depression • Seizure Activity (Propranolol) • Hypoglycemia (Esp in children)

31. BETA BLOCKING AGENTS Range of Toxicity • Calculation is done based on child’s weight, mg amount ingestion and propranolol equivalency dosing. • CONTACT LOCAL POISON CENTER WHILE ON SCENE FOR THIS CALCULATION.

32. BETA BLOCKING AGENTS Equipotency Calculation Mg amount ingestion/child’s weight (KG)/equipotent dose

33. BETA BLOCKING AGENTS Drug Adult Dose Equipotent Dose • Acebutolol 400-800 6.70 • Atenolol 50-200 2.00 • Betaxolol 5-20 2.00 • Bisoprolol 2.5-5 2.00 • Carteolol 2.5-5 2.00 • Carvedilol 24-50 4.00 • Labetalol 200-400 4.00 • Metoprolol 100-450 2.00 • Nadolol 40-320 2.00 • Oxprenolol 120-480 2.00 • Penbutolol 20-80 0.33 • Pindolol 10-60 0.33 • Propranolol 40-480 2.00 • Sotalol 160-480 2-8 6.70 • Timolol 20-60 0.33

34. BETA BLOCKING AGENTS Example Calculation 15 kg child ingested one 50 mg atenolol. 50mg/15mg/2(atenolol BBEC) = 1.66 Child must be transported as BBEC is greater than 1

35. BETA BLOCKING AGENTS Treatment • Contact Poison Center • Activated Charcoal - If available • Consider IV access • Transport

36. Sulfonylureas Oral medications used to lower blood glucose levels. Widely used medication Glypizide, Glyburide

37. Sulfonylureas Mechanism of Toxicity • Lower blood glucose levels - primarily by stimulating endogenous pancreatic insulin secretion. • Secondarily by enhancing the peripheral insulin receptor sensitivity and reducing overall glycogenolysis.

38. Sulfonylureas Clinical Presentation • Hypoglycemia may be delayed in onset • Manifestations of hypoglycemia include: agitation, confusion, tachycardia, seizure activity. • These drugs have a delayed peak and prolonged duration of action.

39. Sulfonylureas Range of Toxicity NO AMOUNT MAY BE SAFLEY OBSERVED AT HOME, MUST BE ADMITTED FOR MIN 23 HOURS

40. Sulfonylureas Treatment • Contact Poison Center • Consider Activated Charcoal • IV Access • Transport • Do not give Glucose unless child has documented hypoglycemia.

41. Camphor Strong smelling essential oil derived from plants. Usually found in over the counter products such as BenGay, Vicks Vapor Rub. Largest percentages is in products such as Campho-Phenique (10.8%) and Camphorated oil (20%)

42. Camphor Mechanism of Toxicity • Rapidly absorbed from GI Tract • CNS stimulant - leads to seizure activity • Exact mechanism is unknown - may be from metabolites.

43. Camphor Clinical Presentation • Oral irritation • Nausea/Vomiting • Typically results in abrupt seizure activity - 20-30 minutes after ingestion • Death may occur from CNS depression or respiratory arrest due to status epilepticus.

44. Camphor Range of Toxicity • Serious symptoms and death have occurred from ingestion of as little as 1 Gram of camphor • This is 10 ml of Campho-Phenique or 5 ml of camphorated oil

45. Camphor Treatment • Contact Poison Center • Protect Airway • Consider Activated Charcoal - must protect airway • Seizure precautions • Transport

46. THEOPYLLINE Older drug used in treatment of asthma Most commonly used in sustained release tablets Absorption may be delayed

47. THEOPYLLINE Mechanism of Toxicity Exact mechanism is not known - antagonist of adenosine receptors. Releases endogenous catecholamines - may stimulate beta-adrenergic receptors.

48. THEOPYLLINE Clinical Presentation • Vomiting • Tremors • Anxiety • Tachycardia • With higher doses will see hypotension and seizures.

49. THEOPYLLINE Range of Toxicity • An acute ingestion of 8-10 mg/kg can raise serum levels by 15-20 mg/L. • Therapeutic serum level are10-20 mg/L • Less than one tablet may be observed at home depending on the child’s weight and the availability of family for follow-up

50. THEOPYLLINE Treatment • Contact Poison Center - determine if dose was toxic • Activated Charcoal • Transport