Post on 16-Dec-2015
OTC Toxicology
Feb. 20, 2003Sarah McPhersonDr. David Johnson
Outline Antihistamines Decongestants Vitamins Iron Caffeine
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????
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 30-60 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 24-72 hr later extensive desquamation,
headache, nausea and vomiting
IIH: headache, blurred vision (from papillitis), diplopia (6th nerve palsy from increased ICP)
Investigations Serum vitamin A level
Elevated to 80-200 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 10-20 mg/kg
< 20 mg/kg toxicity unlikely > 60 mg/kg toxicity likely
Clinical presentation 5 stages:
1. Nausea , vomiting, abdo pain2. 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 200-400mg q4h Lethal dose in adults = 150-200 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 12-24 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