Toxicology

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CHAPTER 30 Toxicology

I. Basic Definitions

A. Toxicology refers to the study of poisons and toxins and how they interact with the body, both internal and external.
B. Clinical toxicology focuses on the toxic effects of therapeutic agents and nontherapeutic agents including drugs of abuse, household products, pesticides, metals, radiation, and other chemicals entities.

II. General Approach

A. ABCs and D

1. Airway
2. Breathing
3. Circulation
4. Decontamination

B. Medical history

1. Medications (Prescription, over-the-counter [OTC], herbals, supplements, vitamins, illicit drugs)
2. Alcohol use
3. Allergies
4. Occupation

C. Physical examination

1. Vital signs: blood pressure, heart rate, respiratory rate, temperature
2. Mouth
3. Pupils
4. Breath sounds
5. Bowel sounds
6. Skin
7. Urination
8. Neurologic exam

D. Laboratory tests and imaging

1. Complete blood cell (CBC) count
2. Electrolytes
3. Urinalysis
4. Blood glucose
5. Blood urea nitrogen (BUN)

E. Diagnosis, antidotes

1. Decontamination

a. Skin

1. Protect yourself
2. Remove clothing
3. Flush with water or normal saline

b. Eye

1. Remove contact lens and discard it
2. Flush with water or normal saline

c. Inhalation

1. Observe for airway obstruction
2. Intubate if necessary

d. Gastrointestinal

1. Induce emesis

a. Syrup of ipecac

1) Consume within minutes of ingestion (30 mL repeated after 20 minutes if ineffective)
2) Contraindicated when the patient is comatose, lethargic, having convulsions, unable to protect his/her airway, caustic or alkali ingestions
3) Rarely given; no longer recommended by the American Association of Poison Control Centers

2. Gastric lavage

a) Use for ingestions of highly toxic substances and substances not well absorbed by active charcoal (lithium, lead, iron); patients with altered mental status or alertness

3. Activated charcoal

a) Cannot bind acids, bases, ethanol (EtOH), methanol, ethylene glycol, hydrocarbons, iron, lead, lithium, potassium, mercury
b) Commonly used for poisonings with carbamazepine, phenytoin, salicylates, digitalis, and theophylline
c) Multiple dosing: 1 g/kg every 2–6 hours
d) Most effective when given within 2 hours of ingestion
e) Most useful for poisons that are enterohepatic recycled
f) Adverse effects: chemical pneumonitis caused by charcoal aspiration

4. Cathartics

a) Purgative agent used to evacuate the bowels
b) Example: sorbitol

III. Specific Toxins and Management

A. Acetaminophen

1. Narrow therapeutic range. Maximum dose: 4 g daily or 90 mg/kg daily (children); lower in patients with hepatic disease or with concomitant alcohol use.
2. Presentation

a. Stage I (0–24 hours): nausea, vomiting (primarily asymptomatic)
b. Stage II, latent stage (24–48 hours): increase in liver function tests (e.g., Alanine Aminotransferase [ALT], Asparate Aminotransferase [AST], and bilirubin)
c. Stage III, hepatic stage (3–4 days): liver failure, jaundice, vomiting, hypoglycemia, renal failure, metabolic acidosis
d. Stage IV, recovery stage (4 days–2 weeks): resolution of hepatic dysfunction

3. Influential factors of toxicity

a. Chronic alcoholics and the elderly are at an increased risk for hepatic disease even at therapeutic doses
b. Glucose 6 phosphate dehydrogenase (G6PD) deficiency

4. Management

a. GI decontamination with activated charcoal
b. Antidote: in patients with toxic blood levels, N-acetylcysteine 140 mg/kg loading dose, then 70 mg/kg every 4 hours for 17 doses

B. Anticholinergics

1. Agents with anticholinergic properties

a. Atropine
b. Antihistamines (e.g., diphenhydramine, meclizine, promethazine)
c. Antipsychotics (e.g., clozapine, thioridazine)
d. Antispasmodics (e.g., dicyclomine, oxybutynin)
e. Tricyclic antidepressants (e.g., amitriptyline, imipramine)
f. Mydriatics (e.g., homatropine)
g. Botanicals (e.g., Atropa belladonna, Datura stramonium)

2. Presentation: dry mucous membranes, altered mental status, flushed skin, mydriasis, fever, tachycardia, hypertension, urinary retention, seizures
3. Laboratory evaluation: no specific diagnostic studies exist
4. Management

a. ABCs
b. GI decontamination
c. Activated charcoal
d. Supportive care

1) Tachycardia: crystalloid infusions
2) Agitation: benzodiazepines
3) Fever: fluids, antipyretics

e. Antidote: physostigmine 2 mg IV at a slow, controlled rate (no faster than 4 minutes)

C. Benzodiazepines

1. Presentation: drowsiness, slurred speech, nystagmus, ataxia, hypotension, coma with respiratory depression
2. Management

a. Gastric lavage
b. Antidote: flumazenil (Romazicon)

1) Used in severe overdose (i.e., comatose patient) and patients with significant cardiorespiratory depression
2) IV dose: 0.2 mg IV in 30 seconds; repeat doses of 0.3 mg in 30 seconds at 1-minute intervals
3) Do not exceed 3 mg in 1 hour
4) Avoid in patients with mixed overdose particularly those who have taken tricyclic antidepressants; flumazenil may induce seizures

D. Digoxin

1. Presentation: nausea, vomiting, diarrhea

a. Acute: asytmptomatic for hours followed by gastrointestinal symptoms; bradydysrhythmias or supraventricular with AV block, high digoxin levels, hyperkalemia, visual changes (halos, blurred vision, changes in color perception)
b. Chronic: altered mental status, flu-like symptoms, gastroenteritis, dysrhythmias, lower potassium levels

2. Complications: hyperkalemia, arrhythmias (initially as sinus bradycardia, followed by atrial tachyarrhythmias with or without heart block)
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