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

Outline Antihistamines Decongestants Vitamins Iron Caffeine

Case #1 18 yo male brought to ED post ingestion of 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????

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

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

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

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

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

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

Decongestants Stimulate peripheral & central  receptors Types of meds: Ephedrine Pseudoephedrine Phenylephrine Phenylpropanolamine tetrahydrozoline

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

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

Case #2 Vitamin case

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

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)

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

Investigations Serum vitamin A level Elevated to ug/dL May be inaccurate for chronic exposures

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

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

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

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

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

Clinical presentation 5 stages: 1. Nausea, vomiting, abdo pain 2. Latent stage (6-24 hr) 3. Shock stage (12-24hr) 4. Hepatic failure (2-3 day) 5. Gastric outlet obstruction for strictures & scarring (2-8 wk)

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)

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

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

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

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

Caffeinism Chronic toxicity Anxiety Tachycardia Diuresis Headache diarrhea

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

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,  agonist,  blocker for hypotension Benzos & CCB for SVT (effect of adenosine blocked) Rx hypokalemia

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

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