OTC Toxicology

1. OTC Toxicology Feb. 20, 2003 Sarah McPherson Dr. David Johnson

2. Outline • Antihistamines • Decongestants • Vitamins • Iron • Caffeine

3. Case #1 • 18 yo male brought to ED post ingestion of 100 50 mg tablets of Diphenhyramine 3 hr ago. • On exam: lethargic, garbled speech, BP 200/90, HR 140, RR 18, T 38.4, flushed dry skin, pupils were 6mm. No focal findings on neuro exam but occasional myoclonic jerks were noted • What is the cause of this guys symptoms and what are you going to do about it????

4. H1 Antihistamines • Bind central & peripheral H1 receptors preventing binding of histamine • Anticholinergic effects • Most well-absorbed orally with peak plasma levels at 2-3 hrs

5. Clinical manifestations • Most present with CNS depression and anticholinergic symptoms • Central anticholinergic symptoms: • Agitation • Hallucinations • Confusion • Sedation • Coma • seizures

6. Clinical Manifestations • Peripheral Anticholinergic symptoms: • Hypertension • Tachycardia • Hyperthermia • Mydriasis • Dry, flushed skin • Urinary retention • ECG: • Sinus tachycardia • Prolonged QRS/QTc

7. How do you manage these?? • Monitored bed, iv, cardiac monitor • Blood to check for coingestion of ASA or Tylenol • Charcoal 1 g/kg orally if possible • Fluids +/- pressors for hypotension • Treat agitation with benzos or physostigmine • Cooling measures for hyperthermia • Treat seizures with benzo’s or phenobarb

8. When should I use physostigmine • Indications: • Peripheral or central anticholinergic symptoms • Narrow QRS • No exposure to 1A or 1C drug • Cointraindications: • The opposite to the above

9. Administering Physostigmine • 1-2 mg slow iv push q 5-10 min • Administer until symptoms resolve and then q 30-60 min with minimum dose to prevent anticholinergic symptoms

10. Decongestants • Stimulate peripheral & central a2 receptors • Types of meds: • Ephedrine • Pseudoephedrine • Phenylephrine • Phenylpropanolamine • tetrahydrozoline

11. Clinical manifestations • CNS stimulation • headache • Hypertension • Tachycardia but may be bradycardic • Rarely cause MI, cerebral hemorrhage, dysrhythmias, ischemic bowel • Low systemic absorption via nasal sprays

12. management • 1g/kg activated charcoal • Benzo’s for seizures, hypertension, and tachycardia • Pentolamine or nitroprusside for hypertension • Lidocaine or propranolol for dysrhythmias

13. Case #2 • Vitamin case

14. Vitamin A • Vit A is stored in the liver (90%) • Toxicity is dependant on dose and duration of exposure • Acute dose of >25,000IU/kg or 4000IU/kg for 6-15 months

15. Effects of too much vit A • Thin skin and brittle nails • Bone abnormalities • IIH (pseudotumor cerebri) • Hepatitis/cirrhosis/portal hypertension • Retinoic acid syndrome (adverse effect of chemo for acute promyelocytic leukemia)

16. Clinical presentation of acute ingestion • Mild GI symptoms and headache • Drowsiness, vomiting, increase intracranial pressure • 24-72 hr later extensive desquamation, headache, nausea and vomiting • IIH: headache, blurred vision (from papillitis), diplopia (6th nerve palsy from increased ICP)

17. Investigations • Serum vitamin A level • Elevated to 80-200 ug/dL • May be inaccurate for chronic exposures

18. Management • Gastric decontamination • Stop vit A • Symptoms of IIH usually resolve in 1 week • If severe IIH then Lasix, Mannitol, Acetazolamide, prednisone and daily lumbar punctures

19. Pyridoxine • Toxicity low because of rapid excretion (water soluble) • Case reports of neuro toxicity with excessive doses (2-4g/d X 2-40 months, recommended daily dose = 2-4 mg) • Symptoms: sensory ataxia, loss of distal proprioception and vibration, diminished or absent DTR…..all resolve when pyridoxine is stopped

20. Niacin • Regular doses cause flushing, vasodilation, headache and pruritis • also causes amblyopia, hyperglycemia, hyperuremia, coagulopathy, myopathy, hyperpigmentation • High doses nausea, diarrhea, hepatitis

21. Iron • Toxic via local and systemic effects • Local GI irritation causes vomiting, abdo pain diarrhea and potentially GI bleed • Metabolic acidosis: • Hypotension from GI loss • Hydrogen ion released in conversion of ferrous iron to ferric • Oxidative phosphorylation disrupted • Direct negative ionotropy to myocardium decreases cardiac output

22. How much iron do you have??? • Ferrous fumarate 33% • Ferrous chloride 28% • Ferrous sulphate 20% • Ferrous gluconate 18% • Toxic doses • Symptoms at 10-20 mg/kg • < 20 mg/kg toxicity unlikely • > 60 mg/kg toxicity likely

23. Clinical presentation • 5 stages: • Nausea , vomiting, abdo pain • Latent stage (6-24 hr) • Shock stage (12-24hr) • Hepatic failure (2-3 day) • Gastric outlet obstruction for strictures & scarring (2-8 wk)

24. Investigations • Xray: only ~ 1/30 cases will be visible in kids, higher is adults but absence of pills on xray does not rule out disease • Labs: • WBC > 15 • Elevated glucose • Iron level at 4-6 hours (peak levels)

25. Management • Initial stabilization • Decontamination: charcoal NOT effective, can try whole bowel irrigation • Antidote: Defuroxamine chelates iron • Indications for defuroxamine: • Metabolic acidosis • Repetitive vomiting • Toxic appearance • Lethargy • Hypotension • GI bleed • Shock • Iron level > 500 ug/dL

26. Disposition • No GI symptoms: observe 6 hours • Develop GI symptoms: admit to ward • Severe symptoms (acidosis, potential hemodynamic instability, lethargy) admit to ICU

27. Caffeine • Bioavailable via all routes • Metabolized to theophylline and theobromine via cytochrome P450 (rate is age dependant) • Therapeutic dose 200-400mg q4h • Lethal dose in adults = 150-200 mg/kg • Death associated with serum level > 80ug/mL

28. Effects of caffeine • GI: nausea and protracted vomiting • Vomiting in 75% of acute theophylline toxicity • CVS: tachycardia, HTN, tachydysrhythmias (SVT), at elevated levels may cause hypotension b/c of beta agonism, cerebral vasoconstriction • Resp: stimulates resp center • Neuro: elevate mood, decreased drowsiness, improved performance on manual tasks, seizures • MSK: increased striated contractility, tremor, myoclonus, rhabdo, wt loss

29. Caffeinism • Chronic toxicity • Anxiety • Tachycardia • Diuresis • Headache • diarrhea

30. Caffeine withdrawal syndrome • Will develop in ~ 50% of coffee drinkers • Onset 12-24 hr post cessation last up to 1 wk • Symptoms: • Headache • Drowsiness • Yawning • Nausea • Rhinorrhea • Lethargy • Disinclination to work • Depression • nervousness

31. Management • Decontamination: • Consider lavage if toxic dose or patient requires intubation • Charcoal: very effective gut dialysis for theophlline(not shown for caffeine MDAC likely useful because of metabolism to theophylline • Rx CVS symptoms • Fluid, a agonist, b blocker for hypotension • Benzos & CCB for SVT (effect of adenosine blocked) • Rx hypokalemia

32. Management • Rx CNS Symptoms: • Benzos • Seizures often resistent to benzos then go to barbs and • Metabolic • Watch for hypo/hyperkalemia and hypocalcemia

33. Enhanced elimination • MDAC : gut dialysis • Charcoal hemoperfusion (most effective) • Hemodialysis (most effective in combo with charcoal hemoperfusion) • Indications for hemoperfusion +/- hemodialysis: • Theophylline or caffeine level > 90 ug/mL • Acute overdose with seizure or CVS compromise • Chronic theophylline or caffeine level > 40 ug/mL AND: • Seizures OR • Hypotension not responding to fluids OR • Ventricular dysrhythmias