Toxicology Handout

Definition: The study of poisonous chemicals, which includes drugs at unsafe doses

Result of Unintentional (80%), Intentional (16%), and Adverse Reactions (4%)

Children are the most common victims of accidental poisoning
Also common among the elderly

Most Common Medication-Related Exposures Percent of Total Cases

1. Analgesics 12.2%
2. Sedatives/Hypnotics/Antipsychotics 10.5%
3. Antidepressants 6.6%
4. Cardiovascular drugs 5.9%
5. Alcohols 4.6%

General Management:
ABC  airway, breathing, and circulation
D: Decontamination
E: Enhanced elimination
F: Focused antidote therapy
G: Get help from a poison control center or toxicologist

Ingestions:
Medication history and reconciliation should be done
Timing and route of the exposure, strengths and amounts
History from family members or other pre-hospital care providers

Toxidrome Signs and Symptoms

Anticholinergic Mydriasis, tachycardia, anhidrosis, dry mucous
membranes, hypoactive bowel sounds, altered
mental status, delirium, urinary retention
Cholinergic Diarrhea, involuntary urination, bronchospasm,
lacrimation, salivation, tachycardia, hypertension
Opioid Sedation, miosis, decreased bowel sounds,
decreased respirations, bradycardia, hypotension
Sympathomimetic Agitation, delirium, myoclonus, mydriasis,
tachycardia, hypertension, hyperthermia

Gastric Decontamination:
Remove toxins to prevent further absorption
Ipecac Syrup – No longer recommended
 MOA: induce vomiting through irritation of the gastric mucosa and chemoreceptor trigger zone
stimulation
 No evidence of increased benefit
Activated Charcoal
 MOA: binds toxins throughout the GI tract to reduce systemic absorption
 Within 60 minutes of ingestion to maximize efficacy
 Alcohol binds poorly (large doses needed which makes it difficult)
 Contraindications: unconscious state or inability to protect airway
Acetaminophen (APAP) Overdose

Most common toxic drug exposure

150 mg/kg or 7.5 g in adults (200 mg/kg in children) considered toxic
Active metabolite NAPQI leads to oxidant cell injury, hepatic failure and death

APAP Overdose Symptom Phases

Phase 1 First 24 hours
Minimal or no signs of distress
Phase 2 24-48 hours
Initial damage to hepatocytes
Right upper quadrant pain, increased ALT/AST,
increased bilirubin
Phase 3 72-96 hours
Peak hepatotoxic effect
Lactic acidosis, acute renal failure, acute
pancreatitis
Phase 4 1 week
Recovery phase

Treatment:
Goal  prevent hepatic toxicity and reduce mortality

Gastric Decontamination
Activated charcoal
 Within first hour after exposure, no vomiting, no AMS
 Do NOT give if patient is sedated and unable to protect airway

N-acetylcysteine (NAC)
MOA: increased synthesis/bioavailabity of glutathione and supply a substrate for sulfation, thereby
increasing the non-toxic metabolism
 Within 8 hours if they can be stratified as having possible or probable hepatotoxicity
 Any length of time if: increased ALT concentration, APAP concentration > 20 mcg/mL
 IV advantageous
1. Decreased administration time (21 hours vs 72 hours)
2. PO “rotten egg” smell/taste

NAC Dosing
Oral Loading: 140 mg/kg

Maintenance: 70 mg/kg every 4 hours for 72

hours (total of 17 doses)
Intravenous Loading: 150 mg/kg (max: 15 g) over 60 min

Maintenance: 50 mg/kg (max: 5 g) over 4 hours,

then 100 mg/kg (max: 10 g) over 16
hours
Methanol and Ethylene Glycol Overdose

Not as common
Methanol: windshield washer fluid, antifreeze, brake fluids, cooking products
Ethylene glycol: antifreeze, de-icing solutions
Calcium Channel Blocker (CCB) & Beta-Blocker Overdose

BB overdose symptoms: hypotension, bradycardia, and prolonged atrioventricular conduction

CCB overdose symptoms: above + lethargy, hyperglycemia, depressed consciousness
Opioid Overdose
Most common associated with toxicologic event: tramadol, oxycodone, methadone, morphine
Most common associated with toxicologic death: methadone, oxycodone, fentanyl, morphine
Symptoms: Respiratory depression (< 12 bpm), coma, miosis, hypoactive bowel sounds

Gastric decontamination – single dose activated charcoal (within first hour, awake, intact airway)
Naloxone
 IV (preferred), IM, intranasal, or via trachea/nebulized
 Initial: 0.4 mg; if no response, repeat dose every 2-3 minutes
 Continuous infusion (2/3 of the effective bolus dose per hour) (naloxone lasts 60-90 mins, shorter
than t1/2 of most opioids)

Digoxin Overdose
Narrow therapeutic index  toxicity reported in as many as 35% of patients on digoxin
Normal therapeutic range 0.8-2.1 ng/mL
Cardiac symptoms: tachyarrhthmias and bradyarrhythmias
Non-cardiac symptoms: N/V, lethargy, headaches, visual disturbances

Gastric decontamination – multidose activated charcoal beneficial

Correct electrolyte abnormalities
 K goal 3.5-4 mEq/L
 Mag goal 1.5-2.2 mg/dL
 Ca goal 8.5-10.5 mg/dL
Treat symptomatic bradyarrhythmias with atropine 0.5 mg

Digoxin Immune Fab (Digifab)

MOA: antibodies that bind to digoxin molecules that are renally excreted
 Life-threatening arrhythmias
 Evidence of end-organ damage
 Hyperkalemia (greater than 5-5.5 mEq/L)

Unknown amount ingested:

 10-20 vials for acute toxicity or 6 vials for chronic toxicity
Known amount ingested:
 Dose (vials) = Total body load (0.8 x mg of digoxin ingested)/0.5
Known digoxin concentration:
 Dose (vials) = [serum digoxin conc (ng/mL) x weight (kg)]/100
 Drug Overdose Symptoms/Treatment
Anticoagulants Phytonadione (Vitamin K)  warfarin
(warfarin, direct thrombin inhibitors, factor Xa Prothrombin complex concentrate (Kcentra) 
inhibitors, heparin, LMWH) warfarin, factor Xa inhibitors
Protamine  heparin, LMWH
Idarucizumab (Praxbind)  dabigatran
Andexant Alfa (Andexxa)  apixaban,
rivaroxaban
Benzodiazepines Flumazenil (Romazicon)
Cyanide Hydroxocobalamin (Cyanokit)
(smoke inhalation, nitroprusside) Sodium thiosulfate + sodium nitrite (Nithiodote)
5-Fluorouracil (5-FU) Uridine triacetate (Vistogard/Xuriden)
Heavy Metals Dimercaprol  arsenic, gold, mercury, lead (with
(arsenic, copper, gold, lead, mercury) calcium disodium edetate)
Penicillamine  copper
Succimer  lead
Hydrocarbons Do NOT induce vomiting
(gasoline, kerosene, mineral oil, paint thinners) Keep NPO to minimize aspiration risk
Insulin and other Hypoglycemics Dextrose injection or infusion
Glucagon
Sulfonylurea-induced  Octreotide (Sandostatin)
Isoniazid Pyridoxine (Vitamin B6)  Benzodiazepines
IV for neurotoxicity symptoms
Iron Deferoxamine (Desferal), Deferiprone
(Ferriprox), Deferasirox (Exjade)
Iron overload from blood transfusions
Methotrexate Leucovorin, glucarpidase
Salicylates Weak base: Acidify the urine
Wake acid: Alkalize the urine
Sodium bicarbonate (alkalinizing agent)
Tricyclic Antidepressants (TCAs) Sodium bicarbonate
Valproic Acid Levocarnitine (Carnitor)
1. A 56-year-old man is admitted to the intensive care unit (ICU) after a β-blocker overdose. After
administering 2 L of 0.9% sodium chloride and 3 g of calcium gluconate, his vital signs are as follows:
BP 70/40 mm Hg, HR 52 beats/minute, and RR 22 breaths/minute. Which therapy is most appropriate at
this time?
A. Glucagon 5 mg.
B. Atropine 1 mg.
C. Insulin 0.1 unit/kg.
D. Dopamine 2 mcg/kg/minute.

2. A 76-year-old woman is admitted to the emergency department (ED) with the chief concern of
decreased mental status. Her vital signs are as follows: BP 118/72 mm Hg, HR 57 beats/minute, and RR
17 breaths/minute. She is experiencing nausea, but her physical examination is otherwise normal. Her
husband is concerned that she may not be taking her medications properly. Given her presentation, which
common toxidrome is most likely in the patient?
A. Anticholinergic.
B. Cholinergic.
C. Opioid.
D. Sympathomimetic.

3. A 57-year-old male patient on the medical floor is incorrectly administered a dose of methadone 40 mg
by mouth that was written for the patient in the adjoining bed. Two hours later, the nurse finds him
unresponsive with the following vital signs: BP 105/67 mm Hg, HR 61 beats/minute, RR 8
breaths/minute, and temperature 98.7°F. The nurse calls for the rapid response team, and as the team
pharmacist, you are asked for a recommendation. Which treatment is most appropriate at this time?
A. Activated charcoal 50 g.
B. Naloxone 0.04 mg intravenously.
C. Whole bowel irrigation.
D. 1 L of 0.9% sodium chloride.

4. A 56-year-old female patient is admitted to the ED after an intentional overdose of 25 amlodipine 10-
mg tablets. She is given activated charcoal 50 g, 2 L of 0.9% sodium chloride, and 3 g of calcium
gluconate. Her current vital signs are as follows: BP 90/50 mm Hg, HR 107 beats/minute, RR 17 breaths/
minute, and temperature 98.7°F. Serum chemistries are as follows: Na 141 mEq/L, K 2.5 mEq/L, Cl 101
mEq/L, HCO3 24 mEq/L, blood urea nitrogen (BUN) 19 mg/dL, serum creatinine (SCr) 0.9 mg/dL, and
glucose 215 mg/dL. The ED physician wants to initiate hyperinsulinemic euglycemic therapy (HIET).
Which is most appropriate to initiate first with respect to HIET?
A. Give insulin 1 unit/kg.
B. Give 50 mL of 50% dextrose in water.
C. Warn the physician that full effects may take up to 30 minutes.
D. Give 20 mEq of potassium chloride intravenously every hour for four doses.

5. The patient in the previous question is not responding to HIET initiation. Her BP remains low at 70/40
mm Hg, and her HR is now 58 beats/minute. Which is most appropriate to initiate at this time?
A. Continue HIET and initiate norepinephrine.
B. Continue HIET and increase the insulin infusion rate
C. Continue HIET and initiate epinephrine.
D. Discontinue HIET and begin intravenous lipid therapy.