Otc toxicology
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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 100 50 mg tablets of Diphenhyramine 3 hr ago.

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OTC Toxicology

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Otc toxicology

OTC Toxicology

Feb. 20, 2003

Sarah McPherson

Dr. David Johnson


Outline

Outline

  • Antihistamines

  • Decongestants

  • Vitamins

  • Iron

  • Caffeine


Case 1

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

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

Clinical manifestations

  • Most present with CNS depression and anticholinergic symptoms

  • Central anticholinergic symptoms:

    • Agitation

    • Hallucinations

    • Confusion

    • Sedation

    • Coma

    • seizures


Clinical manifestations1

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

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

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

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

Decongestants

  • Stimulate peripheral & central a2 receptors

  • Types of meds:

    • Ephedrine

    • Pseudoephedrine

    • Phenylephrine

    • Phenylpropanolamine

    • tetrahydrozoline


Clinical manifestations2

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

management

  • 1g/kg activated charcoal

  • Benzo’s for seizures, hypertension, and tachycardia

  • Pentolamine or nitroprusside for hypertension

  • Lidocaine or propranolol for dysrhythmias


Case 2

Case #2

  • Vitamin case


Vitamin a

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

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

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

Investigations

  • Serum vitamin A level

    • Elevated to 80-200 ug/dL

    • May be inaccurate for chronic exposures


Management1

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

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

Niacin

  • Regular doses cause flushing, vasodilation, headache and pruritis

  • also causes amblyopia, hyperglycemia, hyperuremia, coagulopathy, myopathy, hyperpigmentation

  • High doses nausea, diarrhea, hepatitis


Otc toxicology

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

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

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)


Investigations1

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)


Management2

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

Disposition

  • No GI symptoms: observe 6 hours

  • Develop GI symptoms: admit to ward

  • Severe symptoms (acidosis, potential hemodynamic instability, lethargy) admit to ICU


Caffeine

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

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

Caffeinism

  • Chronic toxicity

    • Anxiety

    • Tachycardia

    • Diuresis

    • Headache

    • diarrhea


Caffeine withdrawal syndrome

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


Management3

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


  • Management4

    Management

    • Rx CNS Symptoms:

      • Benzos

      • Seizures often resistent to benzos then go to barbs and

    • Metabolic

      • Watch for hypo/hyperkalemia and hypocalcemia


    Enhanced elimination

    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


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