BRS Emergency Medicine - L. Stead (Lippincott, 2000)

18. Toxicology Emergencies

I. Evaluation of the Poisoned Patient

§  Evaluation of the poisoned patient consists of thorough diagnostic tests of airway, breathing, and circulation (ABCs), followed by the history and physical examination.

A. Airway

In assessing the airway, evidence of compromise, such as would be suggested by stridor, snoring, loss of the gag reflex, or vomitus in the oropharynx, is looked for.

B. Breathing

The frequency and depth of breathing are noted. Slow, deep breathing may indicate the need for ventilatory support; rapid, shallow breathing may indicate an underlying metabolic acidosis or hypoxemia.

C. Circulation

Blood pressure (BP) and pulse are obtained to assess baseline circulatory status. Bradycardia may indicate cardiotoxicity or parasympathetic overload, whereas tachycardia may be due to cholinergic blockade or central nervous system (CNS) stimulation.

D. History

Because the poisoned patient often presents in a stuporous or at least somewhat altered mental state, obtaining the history may be challenging. It is important to obtain as much information as possible from the paramedics, the patient, the family, and anyone else who was at the scene or who has knowledge of the patient's medical and/or psychiatric history. The objective of the history is to answer the following questions:

1.   What poison is involved?

2.   How much was taken?

3.   By what route was the poison taken (e.g., by mouth, intravenous (IV), skin exposure)?

4.   When was it taken relative to evaluation in the emergency department (ED)?

5.   What else was taken with it? It is important to remember that the most common co-ingestant in adult poisonings is ethanol.

E. Physical examination

1.   Vital signs

§  Any abnormality in vital signs is especially significant in the poisoned patient. Pulse and respiratory rate are determined when the ABCs are checked. It also is important to obtain the temperature and BP. Disturbances in temperature regulation can result from alterations in the CNS (stimulation or depression) and from loss of thermoregulation, often seen with the phenothiazine class of drugs. Hypotension can result from cardiotoxicity, CNS depression, loss of vasomotor tone, and volume depletion (e.g., from diabetes insipidus secondary to lithium, or from diarrhea secondary to organophosphates). Hypertension can result from monoamine oxidase inhibitors (MAOI) overdose, sympathomimetics, and drug withdrawal.

2.   Pupillary size

§  Miosis can be seen in CNS depression, α-adrenergic blockade, and cholinergic stimulation (e.g., opiates, organophosphates, and barbiturates).

§  Mydriasis can be seen in α-adrenergic stimulation and cholinergic inhibition (e.g., atropine, cocaine, and ethanol).

3.   Oral examination

§  The odor of the breath is an important diagnostic clue. Table 18-1 lists the odors commonly associated with certain toxins.

§  Oral examination also permits examinations for burns, as evidence of caustic ingestions and assessment of mucosal hydration. Increased salivation is associated with organophosphates, strychnine, and arsenic, whereas dry mouth is seen with opiates, anticholinergics, and atropine.

Table 18-1. Odors Associated With Specific Toxins




Alcohol, salicylates

Bitter almonds



Gemloxin (water hemlock)


Ethanol, isopropanol, acetone


Arsenic, parathion, organophosphates




Camphor, naphthalene


Chloral hydrate

Shoe polish






4.   Examination of the skin

§  Track marks provide evidence of IV drug use.

§  Cyanosis refractory to oxygen therapy is suggestive of methemoglobinemia.

§  A red or unusually rosy complexion may be due to cyanide, carbon monoxide, boric acid, or anticholinergic poisoning.

§  Dry skin or lack of sweating is associated with anticholinergic poisoning, whereas moist skin indicates cholinergic or sympathomimetic overdose.

5.   Identification of toxidromes

§  Knowledge of the cluster of physical findings associated with a particular class of drug can be especially helpful in deciding the course of action. Knowing the type of drug enables the appropriate treatment and antidote to be administered, if available. Table 18-2 lists the common toxidromes.

Table 18-2. Toxidromes


Examples of toxins



Organophosphates (insecticides)
Some mushrooms

GI upset


Tricyclic antidepressants
Belladonna alkaloids
Anti-parkinsonian medications

Dry mucus membranes
Urinary retention
Flushed skin



Respiratory depression
Pinpoint pupils (miosis)





Many headache and cold medicines




Respiratory depression
Vesicles or bullae

F. Drugs

1.   The “coma cocktail,” administered to patients who are unresponsive, consists of thiamine, dextrose, and naloxone. The cocktail has three components, which commonly reverse many comas. Bedside serum glucose is checked before the cocktail is delivered. Glucose is checked just to make sure coma is not due to non-ketotic hyperosmolar (high sugar) coma. If glucose is high, dextrose should be omitted from the cocktail. The thiamine (100 mg IV) is given before the dextrose (50 g IV push) to prevent Wernicke-Korsakoff syndrome. The naloxone (.01 mg/kg) reverses opiate depression, thereby serving as both a therapeutic and diagnostic tool. Several doses of naloxone may be required for patients with a physiological dependence on opioids, or those who have ingested certain synthetic opiate preparations.

2.   If the patient is acutely agitated or psychotic, a cocktail of 5–10 mg of haloperidol given intramuscularly (IM) and 2–4 mg of lorazepam given IM or IV helps to calm the patient so that more definitive therapy may be instituted.

3.   Antidotes

§  There are antidotes for many of the common poisons encountered in the ED (Table 18-3).

G. Diagnostic tests

1.   Complete blood cell count (CBC): useful for detecting an infection. Absolute leukocytosis also may be produced by iron, theophylline, and hydrocarbons.

2.   Chemistry panel. This is especially useful for calculating the anion and osmolal gaps.

a.   The anion gap (AG) = [Na+ - (HCO3- + Cl-)].

1.   The normal value for an AG is between 8 and 12 mEq/L.

2.   The presence of an elevated AG means that there is an excess of unmeasured anions, resulting in metabolic acidosis. The differential diagnosis of an elevated AG is summarized by the acronym CARTMUDPILES:

§  Carbon monoxide (CO), cyanide, caffeine

§  Aspirin

§  Respiratory dysfunction

§  Toluene

§  Methanol

§  Uremia

§  Diabetic ketoacidosis (DKA)

§  Paraldehyde, phenformin

§  Iron, isoniazid, ibuprofen

§  Lithium, lactic acidosis

§  Ethanol, ethylene glycol

§  Strychnine, starvation, salicylates

b.   The osmolal gap = [calculated osm] - [measured osm].

§  Calculated osm = 2(Na+) + glucose/18 + BUN/2.8


§  Normal serum osm = 275–285

§  An elevated osmolal gap (> 10 mOsm/L) suggests the presence of low-molecular-weight solutes that were not measured. Common solutes include ethanol, methanol, ethylene glycol, isopropyl alcohol, mannitol, and glycerol. An elevated gap, therefore, suggests intoxication with one of these solutes. The gap also can be used to make a rough calculation of the amount of solute ingested.

3.   Arterial blood gases (ABGs) to determine acid–base status. Even the color of the blood—such as the chocolate-colored blood seen in methemoglobinemia—can be helpful.

4.   Abdominal radiograph to look for radiopaque substances. Some of the common radiopaque substances are summarized by the acronym CHIPES:

§  Chloral hydrate

§  Heavy metals (arsenic, lead)

§  Iron, iodide

§  Phenothiazines, psychotropics [tricyclic antidepressants (TCAs)], potassium

§  Enteric-coated, sustained-release preparations

§  Salicylates, salts

5.   Electrocardiogram (ECG) is useful to assess baseline rate and rhythm. Certain drugs have typical toxic patterns on ECG, although these patterns may not be universally present.

 .    Prolongation of QRS: TCAs (typical), phenothiazines, calcium channel blockers (CCB)

a.   Sinus bradycardia/AV block: β-blockers (BB), CCB, TCAs, digoxin, organophosphates

b.   Ventricular tachycardia (VT): cocaine, amphetamines, chloral hydrate, theophylline, digoxin, TCAs

Table 18-3. Antidotes for Common Toxins




N-acetylcysteine (Mucomyst)

Anticholinesterases, organophosphates

Atropine, pralidoxime

Antimuscarinics, anticholinergics


Arsenic, mercury, gold

Dimercaprol, D-penicillamine, British Anti-Lewisite (BAL)

α-adrenergic agonists






Carbon monoxide

100% oxygen, hyperbaric oxygen

Calcium channel blockers

Calcium gluconate




Amyl nitrate + Na-nitrite + thiosulfate


Anti-dig Fab fragments (Digibind)



Iron salts




Lead, arsenic, mercury


Lead, mercury


Methanol, ethylene glycol



Methylene blue*

Neuromuscular blockers




Organophosphates, carbamates

Atropine, pralidoxime

Tricyclic antidepressants


t-PA, streptokinase

Aminocaproic acid


Vitamin K

*Contraindicated in glucose 6-phosphate dehydrogenase deficiency. N-acetylcysteine (NAC) is being used investigationally for treatment of methemoglobinemia in GPD deficient patients.

H. Gastrointestinal (GI) decontamination

1.   Syrup of ipecac. There is very little use for syrup of ipecac. It is definitely contraindicated in caustic ingestions, and unless it will take longer than 1 hour to get from the site of injury to medical assistance, it should not be administered for other ingestions.

2.   Activated charcoal (AC) is the method of choice for GI decontamination. Some drugs do not adsorb to charcoal, however. These include iron, lithium, hydrocarbons, borates, bromides, mineral acids and alkali, and ethanol. AC in these ingestions is not helpful. Drugs with significant enterohepatic circulation, such as theophylline, digoxin, aspirin, and some β-blockers, require multiple doses of AC (MDAC). Dosage is 1 g/kg.

3.   Gastric lavage (GL) is helpful for early presentation of ingestions (within 1 hour) and for recovery of pill fragments. It is not as effective in removing the toxin as AC. It is important to remember to use large-bore orogastric tubes (24–32 French in children, 36–42 French in adults) in order to retrieve pill fragments. GL is contraindicated in patients with an unprotected airway, and in ingestions of alkali. Complications include laryngospasm, aspiration pneumonia, and sinus bradycardia.

4.   Whole bowel irrigation is useful for sustained-release drug preparations, for late presentations, and to aid in massive ingestions in which a significant proportion of the drug may already be in the small bowel. Whole bowel irrigation is accomplished by oral ingestion of a polyethylene glycol electrolyte solution, which decreases transit time via the GI tract without causing electrolyte abnormalities. The dosage is 1.5–2 L/hr (adults), and 25 mg/kg/hr (children). Infusion is continued until the rectal effluent looks the same as the infusate.

5.   Cathartics are solutions of either saline (MgCitrate, MgSO4, NaSO4) or sorbitol that are administered to promote GI motility and enhance GI transit. They can be given in combination with AC or separately. Although they do reduce GI transit time, they have never been shown to improve morbidity or mortality and therefore are not widely used. They have the additional disadvantages of causing moderate electrolyte disturbances, including hypermagnesemia.

II. Acetaminophen

A. Mechanism of action

§  Approximately 10% of acetaminophen (APAP) gets converted in the liver to the toxic metabolite NAPQI, which requires glutathione to be metabolized either back to its precursor, or to less toxic compounds. APAP toxicity is thought to occur when glutathione stores drop to < 30%. Glutathione stores are depleted in many situations that put the patient at increased risk for APAP toxicity. These include malnutrition (as seen in patients with AIDS, cancer patients, and chronic alcoholics) and ingestion of drugs that induce the P450 system, including anticonvulsants, isoniazid, and rifampin.

B. Clinical features

§  Table 18-4 describes the stages of APAP toxicity.

C. Diagnostic tests

1.   Serum APAP level should be obtained 4 hours post-ingestion, when APAP levels peak. If ingestion time is unknown, draw one level immediately and another one in 2–4 hours.

2.   Liver function tests (LFTs), prothrombin time (PT), and bilirubin levels are obtained on initial presentation and several hours afterward to assess extent, if any, of liver damage. Elevated unconjugated bilirubin is suggestive of liver toxicity.

3.   Additional baseline tests that are done include CBC, chemistry panel, and a pregnancy test in women of childbearing age.

Table 18-4. Stages of Acetaminophen Toxicity


Time post-ingestion


1. Initial

0–24 h

Mostly asymptomatic
Mild anorexia, nausea, vomiting, diaphoresis

2. Latent

24–48 h

LFTs and PT begin to increase

3. Hepatic

72–96 h

Hepatic dysfunction peaks
Hepatic failure signaled by vomiting, metabolic acidosis, jaundice, hypoglycemia, coagulopathy, renal failure, and RUQ pain

4. Recovery

4–14 days

Recovery. Symptoms resolve in 3–5 days
LFTs return to normal in 1–3 weeks

LFT = Liver function test; PT = prothrombin time; RUQ = right upper quadrant.

D. Treatment

Figure 18-1. Rumack-Matthew nomogram for acetaminophen poisoning. (Reprinted with permission from Rumack BH, Matthew H: Pediatrics 55:871, 1975.)

1.   AC, with or without a cathartic.

2.   Antidote. N-acetylcysteine (NAC) reverses APAP toxicity by replenishing glutathione stores. The nomogram shown in Figure 18-1 helps determine whether treatment with an antidote is necessary. If the APAP level is ≥ 150 mg/ml at 4 hours post-ingestion, it usually is treated.

a.   Indications for antidote

§  APAP levels taken 4 to 12 hours post-ingestion that fall above treatment line on nomogram

§  Single APAP ingestion of > 140 mg/kg with plasma APAP level unavailable at the time

§  Acute liver failure has developed or is imminent.

b.   Dosage. NAC ideally should be given within 8 hours of ingestion, but can be administered up to 48 to 96 hours post-ingestion. Dosage of oral NAC 5% solution is 140 mg/kg initially, followed by 70 mg/kg every 4 hours, for a total of 17 doses. IV NAC is used in other countries, but is only available as an investigational agent in the United States.

3.   Blood sugar is monitored. Hypoglycemia is treated with a 10%–20% glucose drip.

4.   Ondansetron (0.15 mg/kg every 8 hours, 3 times) or metoclopramide (1 mg/kg for children; 10 mg for adults) to prevent nausea and improve tolerance to NAC

5.   Vitamin K for PT more than 1.5 times normal

6.   Fresh frozen plasma (FFP) for PT more than 3 times normal

7.   Lactulose enemas (30 ml every 6–8 hr) for encephalopathy

8.   Mannitol (0.5 g/kg given over 10 minutes) and fluid restriction for cerebral edema that may result from encephalopathy

E. Disposition

1.   Patients with negligible APAP levels who present after a known period of time following a single ingestion may be discharged home with outpatient follow-up.

2.   Patients with toxic APAP levels, liver damage (per LFTs), who present after an unknown time following ingestion, and who have had multiple ingestions should be admitted to the intensive care unit (ICU).

3.   All patients who have ingested substances with suicidal intent should receive psychiatric evaluation.

F. Prognosis

Poor prognostic factors include:

§  acidosis with pH < 7.3

§  PT > 180 seconds

§  Increasing PT between day 3 and 4

§  PT > 100 seconds with serum creatinine > 3.4 mg/dl

§  Factor V ≤ 10%

III. Salicylates

§  Salicylates include aspirin, many over-the-counter cold medications, certain prescription pain and migraine relievers, and methyl salicylate.

A. Mechanism of action

1.   Respiratory alkalosis: Salicylates increase the sensitivity of the medullary respiratory center to pH and pCO2, resulting in increased alveolar ventilation (hyperventilation).

2.   Emesis and hypokalemia: Salicylates stimulate the medullary chemoreceptor trigger zone, resulting in vomiting and hypokalemia. Compensation for respiratory alkalosis results in increased renal tubule permeability and increased excretion of ions, further exacerbating potassium loss.

3.   Hypoglycemia and hyperthermia: Salicylates disrupt the oxidative phosphorylation pathway, which results in increased heat production and enhanced glycolysis, causing hyperthermia (mild to moderate) and hypoglycemia.

4.   Anion gap metabolic acidosis: The gap comes from accumulation of unmeasured anions such as ketoacids, lactate, and salicylate. Acidosis stems from three different pathways:

a.   Uncoupling of oxidative phosphorylation results in increased lactate production by tissues.

b.   Inhibition of Krebs' cycle results in accumulation of pyruvate and lactate.

c.   As the buffering capability of the body via urinary excretion of bicarbonate and the Hb-OxyHb system dwindles, metabolic acidosis worsens.

d.   Pulmonary and/or cerebral edema are thought to result from increased capillary permeability, although the exact mechanism is unknown. Cigarette smoking and salicylate levels > 40 mg/dl are associated with increased risk of noncardiogenic pulmonary edema.

e.   GI bleed/hemorrhage: Salicylates disrupt the coagulation cascade at cyclo-oxygenase, preventing the formation of thromboxane A2, a factor required for platelet aggregation. Although some degree of prolonged bleeding time is associated with even a single dose of aspirin, hemorrhage is a rare complication of salicylate overdose.

B. Clinical features

§  Acute salicylate ingestion often is associated with suicidal intent but carries a low mortality.

§  Chronic intoxication usually is seen in very young or very old patients, often due to therapeutic mistakes (overdose). Pulmonary and/or cerebral edema, CNS effects, and hyperventilation are more pronounced and more frequent in chronic intoxication.

§  The high mortality (approximately 25%) stems from delay in presentation to the ED, delay in diagnosis (salicylate toxicity is mistaken for other illnesses), and greater systemic acidosis, resulting in higher tissue penetration.

1.   Symptoms may include:

§  tinnitus or hearing loss (reversible)

§  altered mental status

§  lethargy

§  hallucinations

§  seizures

2.   Physical examination findings may include:

§  mild to moderate hyperthermia

§  asterixis

§  tachycardia

§  tachypnea

§  coma

C. Diagnostic tests

1.   Serum salicylate levels correlate poorly with severity of intoxication. Use of the Done nomogram (Figure 18-2) is severely limited, so the treatment plan must be based on the patient's presentation and the dose ingested.

2.   Chemistry panel and serial ABGs to determine acid–base and electrolyte status and to check for hypoglycemia

3.   LFTs and PT to look for hepatotoxicity

4.   Ferric chloride test to look for salicylates: 1 ml of urine is mixed with 1 ml of reagent (Trinder reagent, 40 g HgCl2 with 40 g FeNO3 in deionized water and HCl). A purple color indicates positive test for salicylates.

5.   Urinary pH measurement: alkaline pH of 7.5–8.0 is desired, to promote renal excretion of salicylate.

6.   Pregnancy test for women of childbearing age

Figure 18-2. Done nomogram for salicylate poisoning. (Reprinted with permission from Done AK: Pediatrics 26:00, 1960.)

D. Treatment

1.   ABCs

2.   Hydration with D5NS or D51½2NS to maintain a urine output of 3 ml/kg/hr

3.   Electrolyte abnormalities must be corrected.

a.   Hypokalemia is a particularly bad prognostic factor. It should be corrected with KCl infusions: 40 mEq in 50–250 ml of D5W for 4 to 6 runs.

b.   Hypoglycemia is prevented by adding glucose to IV fluids.

c.   Hypocalcemia can result in tetany. It should be treated with calcium gluconate.

4.   Seizures are treated with IV diazepam.

5.   GI decontamination is important. If the patient presents within 24 hours after ingestion or has taken a sustained-release or enteric-coated preparation, then GL is indicated. It is necessary to use a tube large enough in diameter to recover pill fragments.

6.   AC is given, 1 mg/kg, while results of laboratory studies are awaited. Multiple doses are indicated, because salicylates have large volumes of distribution.

7.   Urine alkalinization promotes salicylate excretion and should be considered in patients with salicylate levels > 35 mg/dl or when clinical toxicity is evident. It is achieved via administration of sodium bicarbonate. Following an IV loading bolus of 1–2 mEq/kg, 3 ampules are added to glucose-containing IV fluids, to run at 1.5 to 2 times maintenance. The aim is to maintain urinary pH at 7.5–8.0. Urinary alkalinization should not be undertaken at the expense of causing serum acidosis, however. Serum pH should be maintained at 7.45–7.50.

8.   Indications for hemodialysis include:

a.   Severe acid–base disturbance

b.   Renal failure

c.   Hepatic failure

d.   Pulmonary edema

e.   Seizures

f.    Coma

g.   Salicylate level > 100 mg/dl in acute ingestions

h.   Salicylate level > 60 mg/dl in chronic ingestions

E. Disposition

1.   Patients who receive AC and are asymptomatic after 6 hours of observation (12 hours for sustained-release preparations) may be discharged home with outpatient follow-up.

2.   Patients who are symptomatic or have toxic levels should be admitted to the hospital, preferably to the ICU, for further management.

3.   All patients who have ingested salicylates with suicidal intent should receive psychiatric evaluation.

IV. β-Blockers

A. Mechanism of action (Fig. 18-3)

§  β-blockers (BB) competitively inhibit endogenous catecholamines at the β receptor, preventing activation of adenyl cyclase, the enzyme responsible for converting adenosine monophosphate (AMP) to cyclic AMP (cAMP).

§  Table 18-5 lists common β-blockers.

B. Clinical features

1.   Symptoms of toxicity usually are evident within 2 hours of ingestion and may include:

§  seizures (propranolol)

§  dizziness

§  fatigue

§  mydriasis

2.   Physical examination findings may include:

§  bradycardia

§  hypotension

§  respiratory depression

§  hypoglycemia

§  bronchospasm (with nonselective agents)

§  VT and ventricular fibrillation (VF)

§  mild hyperkalemia

Figure 18-3. β-blocker action

Table 18-5. Common β-Blockers


β1 selective
















C. Diagnostic tests

1.   Serum levels correlate poorly with clinical toxicity and therefore are of little use.

2.   ECG to look for rate and rhythm disturbances

3.   Cardiac enzymes to look for acute myocardial infarction

4.   ABG and chemistry panel to assess acid–base and electrolyte status

D. Treatment

1.   ABCs (IV, oxygen, monitor!)

2.   AC for early presentations. MDAC should be considered for all drugs that undergo enterohepatic circulation, including BB.

3.   Whole bowel irrigation for sustained-release preparations

4.   Atropine (0.5 mg adults, 0.02 mg/kg children) for symptomatic bradycardia. Atropine should be given immediately, before endotracheal intubation, to prevent unnecessary vagal stimulation. Atropine can be administered IV or via endotracheal tube (ETT).

5.   Glucagon for hypoglycemia and bradycardia

§  Adults: 5–10 mg bolus followed by 2–5 mg/hr infusion

§  Children: 0.05–0.10 mg/kg bolus, followed by 0.05–0.10 mg/hr

6.   Fluids for hypotension: Normal saline (NS) or Lactated Ringer's (LR) is infused at 20–40 ml/kg in an effort to expand intravascular volume.

7.   If hypotension persists despite fluids, a pressor agent is indicated. Infusions are titrated to BP.

a.   Isoproterenol: 4 µg/min (adults) or 0.05–2.0 µg/min (children)

b.   Dopamine: 5–20 µg/kg/min

c.   Epinephrine: 2–10 µg/min (adults) or 0.05–2.0 µg/min (children)

8.   Amiodarone is a phosphodiesterase inhibitor that increases cAMP and enhances contractility by increasing Ca2+ influx. The loading dose is 0.75 mg/kg; infusion rate is 5 µg/kg/min.

E. Disposition

1.   Because BB have a rapid onset of action, an asymptomatic patient at 4 hours post-ingestion (24 hours for sustained-release preparation) can be discharged home with outpatient follow-up.

2.   Symptomatic patients should be admitted to the coronary care unit (CCU).

V. Calcium Channel Blockers

A. Mechanism of action

1.   Inhibition of slow L-type calcium channels in myocardium results in decreased conduction at the sinoatrial node (SAN) and atrioventricular node (AVN).

2.   Inhibition of the fast calcium channels results in decreased myocardial contractility and vasodilation of smooth muscle.

B. Clinical features

1.   Symptoms may include:

§  dizziness

§  apnea

§  somnolence

§  seizures

2.   Physical examination findings may include:

§  metabolic acidosis

§  tachycardia

§  hypotension

§  tetany

C. Diagnostic tests

1.   ECG to look for conduction delays and blocks

2.   Cardiac enzymes to look for acute myocardial infarction

3.   ABG and chemistry panel to assess acid–base and electrolyte status

D. Treatment

§  Treatment is the same as for BB (see section IV D). The only difference is the addition of 10–20 ml of a 10% solution of CaCl2, administered IV, slowly over 10 min, followed by an infusion of 5–10 ml/hr until ECG normalizes and tetany resolves.

E. Disposition

1.   Because CCBs have a rapid onset of action, a patient who is asymptomatic at 6 hours post-ingestion (24 hours for sustained-release preparations) can be discharged home.

2.   Symptomatic patients should be admitted to the coronary care unit (CCU).

VI. Digitalis

§  Digoxin and digitoxin are the most common cardiac glycosides and forms of digitalis. They are compared in Table 18-6. Other cardiac glycosides include oleander, foxglove, and lily of the valley, which also can cause digitalis toxicity. Specifics in this section refer to digoxin, unless stated otherwise.

A. Mechanism of action

§  Digoxin inhibits Na+K+ATPase. The inhibition increases intracellular Na+ and Ca2+ and extracellular K+. Digoxin is used in the treatment of congestive heart failure and atrial fibrillation, where it increases the force of myocardial contraction and decreases conduction velocity through the Purkinje tissue.

B. Risk factors that increase cardiac sensitivity for digoxin include:

§  acute hypoxia

§  hypo- or hyperkalemia

§  hypercalcemia

§  hypomagnesemia

§  respiratory alkalosis

§  acute myocardial infarction (AMI)

§  advanced age

§  direct current (DC) cardioversion

C. Clinical features

1.   Symptoms may include:

§  nausea

§  vomiting

§  malaise

§  blurred vision (chronic)

§  altered mental status (chronic)

§  somnolence (chronic)

2.   Physical examination findings may include:

§  bradycardia

D. Diagnostic tests

Table 18-6. Digoxin vs. Digitoxin


Metabolized by



Enterohepatic circulation

Protein bound



30 h

6.0 L/kg





7 days

0.6 L/kg



VD = volume of distribution

1.   Serum digoxin level 6 hours post-ingestion is drawn to obtain steady-state level, which correlates with toxicity. A level of > 2 ng/ml is considered toxic. (There is considerable overlap between therapeutic and toxic levels.)

2.   Chemistry panel to look for:

a.   Hyperkalemia. Hyperkalemia often is present in acute toxicity. It is treated with glucose, insulin, and bicarbonate, as necessary. Administration of calcium in the setting of digoxin toxicity may be lethal and is therefore contraindicated.

b.   Hypomagnesemia. It is necessary to replace Mg2+, because magnesium has been shown to terminate even refractory VT/VF. Hypermagnesemia may be heralded by loss of deep tendon reflexes, and eventually by respiratory depression.

3.   ECG

a.   Acute findings: AV block and decreased cardiac output. The classic toxic digoxin rhythm is nonparoxysmal tachycardia with 2:1 block. Ventricular dysrhythmias are rare.

b.   Chronic findings: premature atrial junctional tachycardia with all grades of AV block, ventricular automaticity, and extrasystoles.

4.   Chest radiograph to assess patient's volume status. Many patients with congestive heart failure (CHF) easily become fluid overloaded, putting them at risk for pulmonary edema.

5.   Cardiac enzymes to rule out AMI as one of the causes of increased cardiac sensitivity to digoxin.

E. Treatment

1.   ABCs, including continuous cardiac monitoring

2.   Rhythm disturbances must be treated.

a.   Ventricular ectopy and tachydysrhythmias are treated with lidocaine (loading dose of 2 mg/kg IV followed by infusion at 1–4 mg/min) or phenytoin (loading dose of 10 mg/kg IV followed by infusion at 25–50 mg/min).

b.   Symptomatic bradycardia is treated with atropine.

§  Adults: 0.5–1.0 mg every 3–5 min, to a maximum dose of 3 mg

§  Children: 0.01–0.02 mg/kg IV or via ETT if present every 3–5 min, to a maximum dose of 0.04 mg/kg

§  Equipment for transvenous pacing must be ready in case of refractory bradycardia.

3.   GI decontamination

a.   GL for early (within 24 hours of ingestion) presentations. Use may be limited, because it produces vagal stimulation, which may be undesirable.

b.   AC is appropriate for oral overdose. MDAC should be considered for digitoxin due to its large volume of distribution (VD).

4.   Antidote therapy

§  Digoxin-specific Fab fragments are available as an antidote to digoxin poisoning. They prevent digoxin from binding to its receptor.

a.   Indications include:

§  severe, life-threatening dysrhythmias

§  symptomatic bradyarrhythmias unresponsive to atropine

§  coingestion of other cardiotoxic drugs (BB, CCB)

§  serum K+ > 5 mEq/L

§  single ingestions of > 10 mg in adults, 4 mg in children

§  serum steady-state digoxin level > 10 ng/ml in adults, or > 0.5 ng/ml in children

§  cardiac arrest, imminent cardiac arrest, or shock

§  rapid clinical deterioration: progressive obtundation, worsening conduction defects, rapidly increasing serum K+

b.   Disadvantages: the major disadvantage is cost.

c.   Dosing: can be given empirically, or calculated as follows:

§  If amount ingested is known: # vials Fab = (total body load)/VD = (amount ingested × 0.8)/0.6 mg/L given IV

§  If serum steady-state digoxin level is known: # vials Fab = (serum level) × (weight in kg) given IV

§  If neither amount ingested nor serum level is known: 10 vials over 30 minutes for acute ingestions; 4 vials over 30 minutes for chronic ingestions; 20 vials for cardiac arrest

F. Disposition

1.   Patients with acute ingestions who presented early, have received AC, and remain asymptomatic 8 hours post-ingestion can be discharged home.

2.   All patients with chronic ingestion are admitted to the CCU for monitoring.

3.   All patients who have ingested digoxin with suicidal intent are admitted for psychiatric evaluation and cardiac monitoring.

VII. Ethylene Glycol

A. Mechanism of action

§  Ethylene glycol is metabolized to glycolaldehyde and then to glycolic acid and glycolyxic acid. Glycolyxic acid can be broken down into six metabolites, the most toxic of which is oxalic acid. Cofactors pyridoxine and thiamine are required to generate the less toxic metabolites.

B. Toxicokinetics

§  Volume of distribution = 0.8 L/kg

§  Plasma protein binding = 0%

§  Elimination half-life = 3–8 hours

§  Peak plasma level time = 1–4 hours

§  Lethal dose = 1.0–1.5 ml/kg

C. Clinical features

§  The patient with acute ethylene glycol intoxication presents much like one with ethanol intoxication. The clinical picture unwinds in three stages (Table 18-7).

D. Diagnostic tests

1.   Serum levels of methanol, formate, ethylene glycol, and ethanol

2.   Serum osmolarity and serum electrolytes to calculate osmolal gap

3.   ABGs to assess acid base status

4.   Urinalysis to look for calcium oxalate crystals and fluorescence to ultraviolet light

5.   ECG to look for dysrhythmias (rare)

6.   Chest radiograph to look for pulmonary edema

7.   Computed tomographic (CT) scan for patients with severe alterations in mental status

E. Treatment

Table 18-7. Stages of Ethylene Glycol Intoxication


Time of onset post-ingestion

Signs and symptoms

1. CNS stage

30 min–12 h

Slurred speech, ataxia, hallucinations, convulsions, coma

2. Cardiopulmonary stage

12–24 h

Hypertension, tachycardia, tachypnea, congestive heart failure

3. Renal stage

24–72 h

Flank pain, oliguria, crystalluria, acute tubular necrosis, acute renal failure

1.   ABCs. Patent airway must be ensured.

2.   GI decontamination: GL if patient presents within 1 hour of ingestion

3.   Sodium bicarbonate for metabolic acidosis with pH < 7.2

4.   IV fluids and Foley catheter to promote aggressive diuresis

5.   Pyridoxine 50 mg IV every 6 hours to aid in detoxification of metabolites

6.   Thiamine 100 mg IV every 6 hours to aid in detoxification of metabolites

7.   Antidote therapy

a.   Indications include:

§  suspicion of ethylene glycol poisoning

§  metabolic acidosis

§  increased osmolal gap

b.   Fomepizole

§  Fomepizole is a competitive inhibitor of alcohol dehydrogenase.

§  Loading dose is 15 mg/kg infused over 30 minutes.

c.   Ethanol

§  Dosage is 0.8mg/kg followed by an infusion at 130 mg/kg/hr.

§  Serum EtOH levels must be obtained every hour to maintain a target blood ethanol level of 100–150 mg/dl.

8.   Hemodialysis is indicated in the presence of:

§  serum ethylene glycol level > 25 mg/dl

§  acidosis refractory to bicarbonate therapy

§  crystalluria

§  renal failure

§  pulmonary edema

F. Disposition

§  All patients with ethylene glycol ingestions, even if asymptomatic, should be admitted to the ICU, because some of the toxic manifestations may not become evident until as late as 72 hours post-ingestion.

VIII. Methanol

A. Mechanism of action

§  Methanol is oxidized to form formaldehyde and then formate, an ophthalmic toxin that produces metabolic acidosis.

B. Toxicokinetics

§  Volume of distribution = 0.6 L/kg

§  Plasma protein binding = 0%

§  Elimination half life = 14–30 hours

§  Peak plasma level time = 30–90 minutes

§  Lethal dose = 15–30 ml (adults)

C. Clinical features

1.   Symptoms and physical examination findings are much like those seen with ethanol intoxication.

2.   Symptoms may include:

§  euphoria

§  confusion

§  abdominal pain

§  nausea

§  vomiting

§  seizures

§  coma

§  blurred vision

3.   Physical examination findings may include:

§  decreased visual acuity (“snowstorm effect”)

§  slow-reacting pupils, retinal edema, and optic disc hyperemia seen on funduscopic examination

D. Diagnostic tests

1.   Serum levels of methanol, formate, ethylene glycol, and ethanol

2.   Serum osmolarity and serum electrolytes to calculate osmolal gap

3.   ABGs to assess acid–base status

4.   Urinalysis to look for myoglobinuria

5.   Visual acuity testing to evaluate toxicity

6.   ECG to look for dysrhythmias (rare)

7.   CT scan for patients with severe alterations in mental status

E. Treatment

1.   ABCs. Ensure patent airway.

2.   GI decontamination: GL if patient presents within 1 hour of ingestion

3.   Sodium bicarbonate for metabolic acidosis with pH < 7.2. Loading dose is 1–2 mg/kg IV bolus, followed by 3 ampules in 1 L IV fluid, to run at 200–250 ml/hr.

4.   Folic acid 50 mg IV every 4 hours to aid in detoxification of formate

5.   Antidote is ethanol.

a.   Loading dose is 0.8 mg/kg, followed by an infusion at 130 mg/kg/hr until target blood ethanol level of 100–150 mg/dl is reached.

b.   Indications include:

§  peak methanol level > 20 mg/dl

§  metabolic acidosis

§  increased osmolal gap

6.   Hemodialysis is indicated in the presence of:

§  peak methanol level > 50 mg/dl

§  peak formate level > 20 mg/dl

§  acidosis refractory to bicarbonate therapy

§  visual impairment

§  renal failure

F. Disposition

§  All patients with methanol ingestions, even if asymptomatic, should be admitted to the ICU, because some of the toxic manifestation may not become evident until as late as 72 hours post-ingestion.

IX. Tricyclic Antidepressants

§  Tricyclic antidepressants (TCAs) are among the most commonly prescribed drugs in the United States. They are used to treat a variety of conditions, including depression, anxiety, panic disorder, obsessive compulsive disorder, eating disorders, enuresis, attention deficit disorder, chronic pain syndromes, and migraine headache. Their wide use and narrow therapeutic window make them responsible for more intentional drug overdose related deaths than any other prescribed drug.

A. Mechanism of action

1.   Inhibition of fast Na+ channels

2.   K+ channel blockade

3.   Antagonism of ACh at muscarinic receptors

4.   Inhibition of α-adrenergic receptors

5.   Inhibition of GABA receptors

6.   Inhibition of amine uptake

B. Clinical presentation

1.   Na+ channel blockade produces negative inotropy and results in cardiac rhythm disturbances including sinus tachycardia, and wide QRS and PR intervals.

2.   K+ channel blockade results in prolongation of the QT interval.

3.   GABA receptor antagonism can produce seizures.

4.   Antagonism of α-adrenergic receptors causes hypotension with reflex tachycardia.

5.   Inhibition of serotonin uptake can result in myoclonus and hyperreflexia.

6.   Inhibition of norepinephrine produces sympathomimetic effects and may exacerbate cardiac dysrhythmias.

7.   Central antimuscarinic effects include agitation, delirium, hallucinations, slurred speech, ataxia, sedation, and coma.

8.   Peripheral effects include dilated pupils, blurred vision, tachycardia, and decreased secretions (opposite of SLUDGE acronym—See section XX B later in this chapter).

C. Diagnostic tests

1.   ECG to look for prolonged PR, QRS, and QT intervals

2.   ABGs to assess need for mechanical ventilation

3.   Chemistry panel to look for electrolyte abnormalities, especially hypokalemia

D. Treatment

1.   ABCs. Patent airway must be ensured.

2.   GI decontamination. GL may be considered for early presentations; otherwise, AC is used. In most cases 1–2 doses (1 mg/kg) are sufficient.

3.   Sodium bicarbonate infusion for all dysrhythmias

4.   IV fluids for hypotension

5.   Vasopressor infusion (norepinephrine, dopamine) if hypotension is refractory to fluids and bicarbonate

6.   Benzodiazepines for seizures

7.   Flumazenil and physostigmine are contraindicated in the treatment of TCA overdose, because both can induce seizures.

E. Disposition

1.   Patients in stable clinical condition after 6 hours of cardiac monitoring can be discharged home.

2.   Symptomatic patients or patients with cardiac abnormalities should be admitted to the ICU.

3.   All patients with suicidal ingestions should receive a psychiatric evaluation.

X. Lithium

§  Lithium is the drug of choice for bipolar disorder. It also is used in the treatment of schizoaffective disorder and alcoholism, for prophylaxis against cluster headaches, and for chemotherapy-induced leukopenia.

A. Mechanism of action

§  Lithium interferes with hormonal response to cAMP and prevents the reuptake of norepinephrine. It is not known how these mechanisms produce mood stabilization.

B. Toxicokinetics

§  Volume of distribution = 0.6 L/kg

§  Plasma protein binding = 10%

§  Elimination half-life = 25 hours

§  Peak plasma level time = 30 minutes to 2 hours; up to 72 hours in overdose

§  Bioavailability > 95%

§  Toxic dose = 2 mEq/ml, or a single ingestion of 40 mg

C. Clinical features

1.   The main systems affected are the CNS and the kidneys.

2.   Symptoms and physical examination findings may include the following, in order of increasing toxicity:

§  vomiting

§  diarrhea

§  polyuria

§  blurred vision

§  weakness

§  drowsiness

§  vertigo

§  increasing confusion

§  slurred speech

§  muscle fasciculation

§  myoclonus

§  urinary and fecal incontinence

§  restlessness

§  stupor

§  coma

§  seizures

D. Diagnostic tests

1.   Serum lithium level: correlates reasonably well with clinical toxicity

2.   Chemistry panel to monitor electrolytes and renal function. Some degree of renal insufficiency is common with lithium therapy.

3.   Urinalysis and urine electrolytes. High volumes of dilute urine are expected. Lithium interferes with antidiuretic hormone (ADH) and causes a transient nephrogenic diabetes insipidus.

4.   ECG to look for cardiac dysrhythmias (rare)

5.   Thyroid function tests (TFTs). Lithium inhibits thyroid hormone synthesis and metabolites at several stages. Lithium intoxication can worsen preexisting hypothyroidism to the point of myxedema coma.

6.   Pregnancy test for women of childbearing age. Lithium is mildly teratogenic and is associated with Ebstein's anomaly. It should be discontinued prior to all planned pregnancies, and immediately in the case of an unplanned one.

E. Treatment

1.   ABCs

2.   GI decontamination. AC is not useful, because lithium does not bind to charcoal. GL should be considered in early presentations. Whole bowel irrigation is especially useful for sustained-release preparations.

3.   For lithium levels < 2.5 mEq/L, IV saline is useful not only for replacing volume and sodium, but also for enhancing lithium elimination. 1–2 L are given over 6 hours. A Foley catheter is placed to monitor input and output.

4.   With lithium levels > 2.5 mEq/L, or in the presence of significant neurotoxicity or underlying renal or cardiac disease, hemodialysis is the treatment of choice.

F. Disposition

1.   Asymptomatic patients with lithium levels < 2.5 mEq/L may be discharged home after 4–6 hours of observation.

2.   Symptomatic patients or patients with lithium levels > 2.5 mEq/L should be admitted to the CCU.

3.   All patients who have ingested lithium with suicidal intent should receive a psychiatric consult.

XI. Neuroleptics

§  The class “neuroleptics” comprises the antipsychotics, including the phenothiazines, butyrophenones, and thioxanthenes. Examples of drugs in this class are haloperidol, thioridazine, chlorpromazine, clozapine, and thiothixene.

A. Mechanism of action

§  Neuroleptics exert their effects via inhibition of dopamine uptake.

§  Antipsychotic effects are produced by inhibition in the limbic system.

§  Inhibition at the basal ganglia results in the movement disorders associated with neuroleptics.

§  The antiemetic properties of neuroleptics are due to inhibition of dopamine uptake at the chemoreceptor trigger zone. An exception is the atypical neuroleptic clozapine, which exerts its action via a different subclass of dopamine receptors. It has a lower incidence of tardive dyskinesia but carries a risk of agranulocytosis, requiring weekly monitoring of WBCs.

B. Clinical features

1.   The hallmark of neuroleptic overdose is CNS depression, which can range from mild sedation to coma.

2.   Other symptoms and physical examination findings may include:

§  miosis

§  extrapyramidal symptoms (e.g., akathisia, rigidity, dystonia, tremors)

§  seizures

3.   Neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptics, characterized by hyperthermia, muscular rigidity, altered mental status, tachycardia, and labile BP.

C. Diagnostic tests

1.   Serum drug levels are not useful.

2.   Toxicology screen to look for coingestants

3.   Chemistry panel, creatinine kinase (CK), and urinalysis to look for electrolyte abnormalities and rhabdomyolysis

4.   ECG to look for VT/VF, torsades de pointes, and heart block

5.   WBC count for clozapine ingestions to look for agranulocytosis

6.   CT can be considered in cases of altered mental status.

D. Treatment

1.   ABCs. Patent airway must be ensured.

2.   GI decontamination. AC 1 g/kg is administered orally.

3.   IV fluids for dehydration and hypotension

4.   Vasopressors for hypotension. Choices include high-dose dopamine (10–20 (µg/kg/min), norepinephrine, and phenylephrine.

5.   Benzodiazepines or phenytoin for seizures

6.   Lidocaine or external pacing for ventricular dysrhythmias

7.   Magnesium sulfate 2 g IV for torsades de pointes

8.   Diphenhydramine or benztropine for dystonic reactions

a.   Diphenhydramine 25–50 mg every 6 hours (adults) or 5 mg/kg/day (children) IV, IM, or orally

b.   Benztropine 2 mg/day IM or IV

c.   Symptoms resolve in 15–30 minutes. Medication should be continued for 48–72 hours longer in order to prevent further episodes.

9.   ED treatment of NMS: ABCs, benzodiazepines to relieve muscular rigidity, cooling measures, and intubation with neuromuscular blockade as necessary

E. Disposition

1.   Patients who are asymptomatic 4 hours post-ingestion can be discharged home.

2.   Patients with CNS or respiratory depression, seizures, or cardiac dysrhythmias should be admitted to the ICU.

3.   Patients with non–life-threatening symptoms should be admitted to a monitored bed.

4.   All patients who have ingested neuroleptics with suicidal intent should receive psychiatric evaluation.

XII. Benzodiazepines

A. Mechanism of action

§  Benzodiazepines stimulate the inhibitory neurotransmitter γ-aminobutyric acid (GABA), which binds to the GABAb receptor, opening the chloride channels. The equalization of gradient prevents further nerve impulses from being conducted.

§  Many drugs belong to the benzodiazepine group, each of which has a different duration of action and varying sedative, anxiolytic, anticonvulsant, and muscle relaxant properties. Table 18-8 compares some of the more common preparations.

B. Toxicokinetics (see Table 18-8)

Table 18-8. Toxicokinetics of Common Benzodiazepines


Generic name

Trade name

Half-life (h)

VD (L/kg)

Peak serum concentration (no. hours post-ingestion)

Protein binding (%)






















VD = volume of distribution

C. Clinical features

1.   The patient with benzodiazepine overdose presents with signs of CNS depression.

2.   Symptoms and physical examination findings may include:

§  drowsiness

§  lethargy

§  apathy

§  ataxia

§  short-term memory loss

§  hypotonia

§  hypotension

§  respiratory depression

§  coma

D. Diagnostic tests

1.   Serum benzodiazepine levels do not necessarily correlate with clinical toxicity and therefore are not useful for management.

2.   Urine toxicology screen to look for coingestants

3.   Bedside glucose testing to look for hypoglycemia

4.   ECG to look for dysrhythmias (rare)

E. Treatment

§  Pure benzodiazepine overdose is almost never fatal. Only supportive treatment is required, because it wears off and resolves in 12–36 hours.

1.   ABCs. Patent airway must be ensured.

2.   IV fluids for BP support

3.   AC for GI decontamination

4.   Antidote therapy. Flumazenil is a competitive inhibitor of benzodiazepines that binds to the same GABAb receptor. It reverses all effects of benzodiazepines. Use of flumazenil usually is limited to reversal of benzodiazepine-induced anesthesia (conscious sedation) for minor surgical procedures. The major adverse effect of flumazenil is seizure activity. It is therefore contraindicated in patients in the following categories:

a.   those who are on benzodiazepine therapy for seizure prophylaxis

b.   patients who chronically use or abuse benzodiazepines for their anxiolytic effect

c.   patients who have ingested combinations of benzodiazepines and drugs that are epileptogenic, such as TCAs and antihistamines

F. Disposition

1.   Asymptomatic patients who are awake following a pure benzodiazepine overdose can be discharged home.

2.   Patients with mixed ingestions, patients with respiratory or CNS depression, and patients who received flumazenil should be admitted.

XIII. Cocaine and Amphetamines

A. Mechanism of action

§  The euphoria and “power high” are due to sympathetic nervous system (SNS) stimulation. Cocaine and amphetamines stimulate the release of norepinephrine while blocking its reuptake. The blockade floods synapses with neurotransmitter, causing sustained stimulation of the postsynaptic receptors.

B. Clinical features

1.   Symptoms may include:

§  mydriasis

§  euphoria

§  agitation

§  paranoia (cocaine)

§  visual hallucinations

§  formication (cocaine)

§  hyperthermia

§  tremor

§  seizures

§  chest pain

§  palpitations

2.   Physical examination findings may include:

§  tachycardia

§  hypertension

§  tachypnea

§  dyspnea

C. Diagnostic tests

1.   Urine toxicology screen to confirm drug ingestion and to look for coingestants

2.   Cardiac enzymes and ECG: over 50% of patients who present to the ED with chest pain following cocaine abuse have AMI.

3.   ABG: to determine acid–base status and to look for A-a gradient if pulmonary pathology is suspected

4.   CBC, chemistry panel, LFTs, and coagulation studies to rule out other causes for presentation, including infection and ethanol withdrawal

5.   Chest radiograph to look for pneumothorax, pulmonary edema, and pneumonia

6.   Abdominal radiograph to look for cocaine packets in body packers

7.   Blood cultures in patients who are septic or who have a new-onset cardiac murmur. IV drug abusers are at increased risk of endocarditis.

8.   Urinalysis to look for RBC, Hb, rhabdomyolysis

9.   Pregnancy test in women of childbearing age: cocaine is a known teratogen, and use should be discontinued immediately upon discovering pregnancy.

D. Treatment

§  There is no specific treatment for cocaine or amphetamine overdose.

§  Treatment is directed at addressing individual manifestations and complications.

§  Benzodiazepines are the mainstay of treatment, controlling agitation, seizures, tachycardia, and hypertension. The drug of choice is diazepam. Alternatives to diazepam include lorazepam (0.05 mg/kg IV) and midazolam (0.2 mg/kg IV). Other drugs may be used in addition to benzodiazepines if they are not sufficient on their own.

1.   ABCs. Supplemental oxygen is given for increased myocardial demand.

2.   Diazepam 2.5–10 mg IV push every 5 minutes as needed to control anxiety, agitation, tachycardia, hypertension, and hyperthermia

3.   Advanced Cardiac Life Support (ACLS) protocol for cardiac arrest, myocardial infarction

4.   Phenytoin 15 mg/kg IV slowly, or diazepam, for seizures. (Dosing for diazepam for children under 5 years of age: 0.05–0.3 g over 3 minutes, maximum dose 5 g; for children over 5 years of age: same dose, maximum dose is 10 g; adults: 10 mg every 15–30 minutes, maximum dose is 30 mg)

5.   Lidocaine 1 mg/kg loading dose, then 2–4 mg/kg infusion for ventricular dysrhythmias

6.   Ice baths, cool water mist with fanning to promote evaporative loss for hyperthermia

7.   Nitroprusside drip 0.5–10 mg/kg/min IV for malignant hypertension

8.   For body packers: GI decontamination including AC, gastric lavage, and whole-bowel irrigation with cathartics are appropriate. In cases of rupture, emergent abdominal laparotomy is required.

9.   Certain drugs should be used with caution or avoided in the treatment of sympathomimetic overdose. These include:

a.   β-blockers—which can potentiate coronary artery vasoconstriction and aggravate bronchospasm

b.   Aspirin—which binds to protein-bound thyroxine and may aggravate missed thyroid storm and hyperthermia

c.   Haloperidol and phenothiazines—which may increase risk of seizures and malignant hyperthermia

E. Disposition

1.   Asymptomatic patients may be discharged after 4–6 hours of observation.

2.   Patients with evidence of cardiac or neurologic dysfunction (AMI, CVA) should be admitted to the ICU.

3.   Symptomatic patients without evidence of cardiac or neurologic dysfunction can be admitted to the regular ward.

4.   All patients should be referred to drug counseling and rehabilitation.

5.   All patients who have ingested cocaine or amphetamines with suicidal intent should have a psychiatric evaluation.

XIV. Phencyclidine (PCP)

A. Mechanism of action

§  PCP acts as a false neurotransmitter, preventing the reuptake of dopamine, 5HT, norepinephrine, and GABA. The psychoactive effect is due to the inability of the brain to translate sensory input into meaningful behavior.

B. Clinical features may include:

§  nystagmus

§  hypertension

§  normal-sized pupils

§  blank stare

§  violent agitation

§  confusion

§  profuse diaphoresis

§  cholinergic signs

C. Diagnostic tests

1.   Toxicology screen to document ingestion and look for mixed ingestions

2.   Urinalysis and CK to look for rhabdomyolysis

3.   Chemistry panel to look for hypoglycemia and electrolyte abnormalities

D. Treatment

1.   Physical and chemical restraint for violently agitated patients. Haloperidol 5–20 mg IM is used for chemical restraint.

2.   ABCs

3.   Sedation with benzodiazepines to control tachycardia, hypertension, anxiety, and seizures

4.   Sodium nitroprusside for life-threatening hypertension

5.   Fluids and urine alkalinization with sodium bicarbonate for rhabdomyolysis

E. Disposition

1.   Patients with life-threatening symptoms and violent agitation beyond 4 hours should be admitted to the hospital.

2.   Patients who are stable and without agitation or psychoses following 4–6 hours of observation can be discharged home.

XV. Lysergic Acid Diethylamide (LSD)

A. Mechanism of action

§  Inhibition of 5HT release at the postsynaptic neuron

B. Toxicokinetics

§  Half-life: 4 hours

§  Onset of action: 30 minutes

§  Duration of psychoactive effects: 12 hours

§  Drug is marketed in mg quantities, so overdose is rare. Pure LSD intoxication rarely is fatal.

C. Clinical features

1.   Symptoms may include:

§  euphoria

§  visual hallucinations

§  loss of boundaries between self and the world, making everything fascinating and awe-inspiring

2.   Physical examination findings may include:

§  mydriasis

§  tachycardia

§  mild hypertension

3.   The environment in which the user takes the drug impacts the experience. The same drug taken in a threatening environment can produce an intensely frightening experience (a “bad trip”) instead of a “beautiful” one.

D. Diagnostic tests

§  No specific diagnostic tests are necessary if the diagnosis is clear. If the diagnosis is unclear, proceed with a general toxicology work-up.

E. Treatment

§  The mainstay of treatment involves reassurance and the provision of a relaxing, non-threatening atmosphere. Benzodiazepines help in alleviating anxiety.

F. Disposition

1.   Most patients calm down after a few hours of observation and can be discharged home.

2.   Patients with persistent anxiety, massive ingestions, or mixed ingestions should be admitted.

XVI. Opioids

§  The opioids are a group of drugs that are widely used therapeutically for analgesia and anesthesia but unfortunately also have high abuse potential. Examples of drugs in this group include heroin, methadone, codeine, morphine, meperidine, fentanyl, and propoxyphene.

A. Mechanism of action

§  Opioids bind competitively to opioid (mu, kappa, delta) receptors to produce decreased affective pain perception by reducing neurotransmitter release, mimicking endorphins.

B. Toxicokinetics

§  See Table 18-9 for toxicokinetics of common opioids.

C. Clinical features may include:

§  miosis (note: meperidine may cause pupillary dilatation secondary to its antimuscarinic activity).

§  respiratory depression

§  coma

§  euphoria

§  nausea

§  vomiting

§  pruritus

§  seizures (meperidine and propoxyphene)

§  noncardiogenic pulmonary edema (NCPE)(heroin)

§  cardiac dysrhythmias (propoxyphene)

Table 18-9. Toxicokinetics of Common Opioids


Duration of action

Weak analgesic agonist

2 h
4 h

Strong analgesic agonist

30 min
2 h
4 h
4 h
6–8 h


< 5 min

D. Diagnostic tests

1.   Serum drug levels are not useful for immediate management.

2.   ABGs to assess need for mechanical ventilation

3.   ECG for suspected propoxyphene ingestion

4.   Chest radiograph for suspected heroin ingestion

5.   Pregnancy test for all women of childbearing age. Many opioids are teratogenic.

E. Treatment

1.   ABCs. Patent airway must be ensured. 100% oxygen may be administered.

2.   Antidote therapy: Naloxone (both diagnostic and therapeutic)

§  In adults: 0.4 mg test dose for diagnosis, then 2 mg every 3 minutes to a total of 10 mg until patient is awake

§  In children: 0.01 mg/kg, repeated as necessary to a maximum of 0.2 mg/kg

3.   Loop diuretics for NCPE

4.   Antiarrhythmics for dysrhythmias. Class Ia drugs (e.g., quinidine, procainamide) should be avoided.

F. Disposition

1.   Known heroin abusers who respond to naloxone and remain without respiratory depression for 6 hours can be discharged home.

2.   Patients with long-acting ingestion (methadone) should be admitted.

3.   Patients who sustained hypoxia secondary to opioid overdose should be admitted for 24 hours of observation.

4.   All patients should receive referral for drug counseling and rehabilitation.

5.   All patients who have ingested opioids with suicidal intent require psychiatric evaluation.

XVII. Iron Toxicity

A. Mechanism of action

§  Iron toxicity is the condition of free iron present in the circulation. This occurs after 100% of transferrin becomes saturated and results in tissue penetration of iron.

B. Clinical features

§  Clinical features can range from mild GI upset to severe cardiovascular collapse, depending on the amount ingested. Mild symptoms occur with ingestions of 20 mg/kg or less. Moderate symptoms are associated with ingestions of 20–60 mg/kg, and severe toxicity is seen with ingestions exceeding 60 mg/kg. Table 18-10 summarizes the stages of acute iron poisoning. Note that not all stages occur in all patients.

C. Diagnostic tests

1.   Serum iron levels. The first level should be drawn 3–5 hours post-ingestion, or immediately if time of ingestion is unknown. A second level is drawn 6–8 hours post-ingestion to account for sustained-release preparations. A serum level of < 350 µg/dl indicates minimal toxicity, whereas a level > 500 µg/dl is potentially fatal. Because iron is rapidly metabolized, serum levels can be deceptively low, even as the patient is going into shock.

2.   CBC to look for leukocytosis. A white cell count > 15,000 in the presence of hyperglycemia suggests high serum iron levels, and warrants antidote therapy.

3.   ABGs to assess need for mechanical ventilation

4.   Chemistry panel to look for hyperglycemia and electrolyte imbalances

5.   PT/APTT and LFTs to look for liver dysfunction

6.   Abdominal radiograph: iron is radiopaque unless it is completely dissolved.

Radiographs are useful to assess the amount of the ingestion and the effectiveness of GI decontamination.

7.   Type and crossmatch for cases of severe toxicity where transfusion may become necessary

Table 18-10. Stages of Iron Toxicity


Time after ingestion

Signs and symptoms

I. Initial

0–6 h

Tachycardia, tachypnea, metabolic acidosis, hypotension, nausea, vomiting, diarrhea, seizures, lethargy, coma

II. Pseudo-recovery

6–24 h

Patient appears clinically stable

III. Recurrent

12–48 h

Anion gap metabolic acidosis, hyperglycemia, cyanosis, pulmonary edema, hypotension, cardiovascular collapse, leukocytosis, gastrointestinal bleeding, lethargy, seizures, coma

IV. Hepatic

2–5 days

Acute hepatic failure, coagulopathy, hypoglycemia

V. Late

2–7 wk

Small bowel obstruction, gastrointestinal scarring, stricture formation

D. Treatment

1.   ABCs

2.   GI decontamination

§  AC is useless because iron does not adsorb to charcoal.

§  GL with NS is indicated. It is necessary to use a tube with a diameter large enough to retrieve pill fragments.

§  Whole bowel irrigation is helpful when abdominal radiograph reveals iron tablets retained in the stomach or small bowel.

3.   Antidote therapy: Deferoxamine mesylate should be administered to all symptomatic patients, without waiting for serum levels. If patients are asymptomatic, a deferoxamine “challenge” of 50 mg/kg IM or 10 mg/kg IV over 1 hour is administered. If the urine turns a “vin rosé” color (reddish brown) or changes color at all, the test is considered positive, and antidote therapy should be administered to the patient despite being asymptomatic. Dosages are:

a.   IV: 15 mg/kg/hr. Hypotension and rash should be checked for.

b.   IM: 40–90 mg/kg up to a maximum of 6 g/day. Injections should be administered 4–12 hours apart.

c.   Antidote therapy should be continued until the urine is clear and the patient becomes asymptomatic.

4.   Exchange transfusion for severely symptomatic patients and for those with serum iron levels > 1000 µg/dl

5.   Hemodialysis for patients who develop shock or coma

E. Disposition

1.   Patients with serum iron levels < 300 mg/dl, who remain asymptomatic 6 hours post-ingestion can be discharged home.

2.   Patients with severe toxicity should be admitted to the ICU.

XVIII. Carbon Monoxide

A. Mechanism of action

§  Carbon monoxide (CO) competes with oxygen for hemoglobin (Hb) with 250 times the affinity of oxygen, resulting in hypoxia to all tissues. Historical clues that may point to CO poisoning include confined space fires, presentation of several household members who are sick at the same time, history of a car engine left on, malfunctioning furnaces, and cold weather.

B. Toxicokinetics

1.   Elimination: 100% via lungs

2.   Half-life

§  320 minutes on room air

§  82 minutes on 100% oxygen via non-rebreather mask

§  23 minutes on 3.0 atmospheres of hyperbaric oxygen (HBO)

C. Clinical features

1.   Symptoms, in order of severity, may include:

§  headache

§  nausea

§  vomiting

§  malaise

§  chest pain

§  weakness

§  apathy

2.   Physical examination findings, in order of severity, may include:

§  cherry red skin

§  abnormal reflexes

§  altered mental status (may be subtle)

§  hypotension

D. Diagnostic tests

1.   Carboxyhemoglobin (CoHb) level makes the diagnosis.

2.   ABGs to look for low O2 saturation. Pulse oximetry in the setting of CO poisoning will reveal a falsely normal O2 saturation.

3.   ECG and cardiac enzymes to look for myocardial damage

4.   Head CT to look for white matter changes (poor prognosis) and to rule out other causes of altered mental status

5.   Chemistry profile to look for metabolic acidosis

6.   Methylated hemoglobin and cyanide levels may be checked, based on clinical suspicion.

E. Treatment

1.   ABCs. Oxygen is the cornerstone of therapy. Oxygenation with a 100% non-rebreather mask should be done.

2.   HBO therapy

a.   Indications include:

§  asymptomatic patients with CoHb levels > 20%

§  symptomatic patients (e.g., neurologic impairment, ischemia/chest pain, nausea, vomiting, headache)

§  pregnant patients

§  patients who experienced loss of consciousness (syncope)

b.   Risks and complications include:

§  barotrauma in closed spaces (including sinus, middle ear, and stomach)

§  O2 toxicity (convulsions, pulmonary edema)

F. Disposition

1.   Patients who are asymptomatic and have a normal ECG can be discharged after 4–6 hours of observation.

2.   All patients with chest pain, ECG changes, or altered mental status should be admitted.

XIX. Anticholinergics

A. Mechanism of action

§  Anticholinergic drugs such as atropine, scopolamine, benztropine, and diphenhydramine inhibit muscarinic cholinergic receptors at parasympathetic end-organs. Muscarinic receptors regulate sweat, salivary, and mucosal gland activity and are present in the smooth muscle of the eye, the GI tract, and the urinary bladder.

§  Excessive stimulation of these receptors results in the cholinergic syndrome discussed in section XIX B.

§  Cholinergic receptors in the myocardium regulate AVN conduction.

B. Clinical features

1.   The clinical features of a patient with anticholinergic poisoning can be summarized with the following expression: mad as a hatter, dry as a bone, red as a beet, blind as a bat, and hot as Hades.

2.   Symptoms may include:

§  absence of sweating

§  flushed skin

§  fever

§  altered mental status

§  hallucinations

3.   Physical examination findings may include:

§  mydriasis

§  dry mucous membranes

§  decreased bowel sounds

§  bladder distention

C. Diagnostic tests

1.   Serum drug levels are not useful. Because many over-the-counter preparations of anticholinergics include APAP or aspirin, however, APAP and salicylate levels may reveal a mixed poisoning.

2.   ECG to look for dysrhythmias (rare). Usually only sinus tachycardia is seen.

3.   ABGs to look for signs of respiratory compromise (rare)

4.   CBC and chemistry panel as part of general work-up

D. Treatment

1.   ABCs. Patent airway must be ensured.

2.   Benzodiazepines for agitation

3.   Cooling measures and antipyretics for hyperthermia

4.   GI decontamination: MDAC is indicated.

5.   Antidote therapy: Physostigmine is an anticholinesterase inhibitor that can reverse both the peripheral and central effects of anticholinergic drugs. Use of physostigmine should be limited to patients with seizures, severe hallucinations, or delirium.

a.   Dosage is 1–2 mg for adults and 0.5 mg for children infused IV slowly. Dose can be repeated if needed (rare).

b.   Contraindications

§  Significant conduction abnormalities on ECG

§  Evidence or suspicion of TCA or other cardiotoxic drug ingestion

E. Disposition

1.   Patients who have received AC and have been symptom-free for 6 hours in the ED can be discharged home with outpatient follow-up.

2.   Patients with moderate to severe symptoms, or those who required physostigmine, should be admitted to a monitored bed.

3.   Psychiatric evaluation for all suicidal ingestions

XX. Organophosphates

§  Organophosphates are a class of compounds commonly found in pesticides and weapons of mass destruction such as nerve gas.

A. Mechanism of action

1.   Competitive inhibition of acetylcholinesterase (ACE) results in prolongation of the actions of acetylcholine (ACh).

2.   ACh acts at three different types of receptors:

a.   Nicotinic: sympathetic, parasympathetic, skeletal muscle

b.   Cholinergic: postganglionic sympathetic (e.g., sweat glands)

c.   Muscarinic: parasympathetic

B. Clinical features

1.   The clinical features of a patient with cholinergic poisoning are summarized in the acronym SLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis).

2.   Other symptoms and physical examination findings may include:

§  rhinorrhea

§  excess bronchial secretions

§  miosis

§  involuntary twitches

§  muscle fasciculations

§  rancid breath and vomitus

C. Diagnostic tests

1.   RBC cholinesterase levels represent “true” levels of activity, whereas plasma levels represent “pseudo” levels and are not as accurate. Unfortunately, tests are not readily available for either level in many hospitals. If available, serial levels should be obtained to assess toxicity.

2.   ABG to assess respiratory status

3.   ECG to look for dysrhythmias (rare)

4.   CBC, chemistry panel, and LFTs as part of the general work-up

D. Treatment

1.   ABCs. Suctioning of secretions and maintaining the airway are especially important.

2.   Dermal decontamination. The patient's clothing must be removed and the exposed skin flushed thoroughly with water. This is extremely important to reduce chances of health care worker poisoning.

3.   GI decontamination: may be of limited benefit because of the rapid absorption of organophosphates and carbamates. May be more appropriate in the pre-hospital setting.

4.   Atropine: given until control of secretions is achieved. Dosage is 2–5 mg IV push every 5 minutes for adults and 0.05 mg/kg in children. Atropine effect produces tachycardia and mydriasis, and works only on muscarinic receptors.

5.   Pralidoxime: reverses effects at both nicotinic and muscarinic receptors. Dosage is 1 g IV in adults, 20–40 mg/kg IV in children (maximum dose is 1 g for both adults and children). Dose can be repeated in 1 hour and then again every 6–8 hours over a 48-hour period until signs and symptoms resolve. Best if administered within first 24 hours.

6.   Benzodiazepines for seizures

E. Disposition

1.   Patients with minimal exposure who remain asymptomatic 6–8 hours post-ingestion can be discharged home.

2.   Symptomatic patients and those who received antidote therapy should be admitted to the ICU. Full recovery generally occurs within 10 days.

XXI. Carbamates

A. Mechanism of action

§  Carbamates are another class of anticholinesterase inhibitors. Their major difference from organophosphates is their short duration of action and reversible (transient) inhibition of cholinesterase, resulting in lesser toxicity than organophosphates.

B. Clinical features

§  are the same as for organophosphates (see section XX)

§  Pralidoxime is not administered for pure carbamate poisoning, because patients are not sick enough to need it (risk vs. benefit ratio).

C. Diagnostic tests

§  are the same as those for organophosphates (see section XX C)

D. Treatment

§  is the same as that for organophosphates (see section XX D)

§  The only exception is that the use of pralidoxime in pure carbamate poisoning is controversial, and thus not usually given. However, it is not withheld in cases where mixed or uncertain ingestions are suspected.

E. Disposition

§  Due to the short duration of action of carbamates, patients are rarely symptomatic beyond 6–8 hours, and most can be discharged home safely.

XXII. Corrosive Ingestions

§  Corrosive ingestions include strong acids such as HCl, H2SO4, and H3N, and strong alkalis such as NaOH and KOH.

A. Mechanism of action

§  Acids exert their effect via a coagulation necrosis, which has a slow penetration.

§  Alkalis exert their effect via a liquefaction necrosis, which has a more rapid penetration.

B. Clinical features

1.   Acids

§  Acute complications of acid ingestion include corrosive gastritis, hemorrhage, and perforation.


§  Delayed complications include gastric outlet obstruction and achlorhydria.

§  The esophagus is mostly spared in acid ingestions.

2.   Alkalis

§  Esophageal injury is prominent.

§  Acute manifestations include perforation and infection.

§  Delayed complications include strictures and altered motility.

C. Diagnostic tests

1.   CBC, chemistry panel for significant ingestions

2.   ABGs to assess need for mechanical ventilation

3.   Type and crossmatch for significant blood loss

4.   Chest and abdominal radiographs to look for perforation

D. Treatment

1.   For both acid and alkali ingestions:

a.   ABCs. Patent airway must be ensured.

b.   Haloperidol for acute psychosis as needed

c.   Narcotic analgesia as needed

d.   Endoscopy to determine severity of injury

e.   Methylprednisolone, 125 mg IV, for injuries that penetrate the mucosa

f.    Antibiotic coverage of oral flora if infection is anticipated or if steroids are used

2.   For acid ingestions:

a.   Emetics, AC, and neutralizing solution are contraindicated.

b.   Ice water GL is indicated.

3.   For alkali ingestions:

a.   Ingested foreign body (e.g., alkaline battery) should be removed.

b.   GL is contraindicated.

E. Disposition

1.   Patients who are asymptomatic 6 hours post-ingestion may be discharged home.

2.   Symptomatic patients should receive endoscopic evaluation, which may require admission.

3.   All patients who have ingested acid or alkali substances with suicidal intent should receive psychiatric evaluation.

Review Test

1. A 72-year-old woman has a shoulder dislocation reduced in the emergency department (ED) under a conscious sedation protocol that used midazolam and fentanyl. Ten minutes after successful reduction of the shoulder, the patient is still quite lethargic. You decide to try a dose of flumazenil. Which of the following is the mechanism of action of this drug?

(A) Competitive inhibition of benzodazepines at GABA inhibitory receptors

(B) Competitive inhibition of barbiturates at GABA inhibitory receptors

(C) Non-competitive inhibition of benzodiazepines at GABA stimulatory receptors

(D) Non-competitive inhibition of barbiturates at GABA stimulatory receptors

(E) Up-regulation of benzodiazepine receptor sites

1-A. Flumazenil is a benzodiazepine antidote that works via competitive inhibition of GABA inhibitory receptors. Because of its major adverse effect of producing seizures, its use is limited to situations where the cause of altered mental status, lethargy, or coma is known to be a pure benzodiazepine ingestion, such as iatrogenic administration for conscious sedation protocols or witnessed pediatric ingestions (See section XII A).

2. In which of the following situations may flumazenil be used?

(A) A patient with a history of seizure disorder treated with benzodiazepines

(B) A patient with a history of anxiety disorder treated with benzodiazepines

(C) A patient with a history of chronic benzodiazepine use/abuse

(D) A patient with a concomitant tricyclic antidepressant ingestion

(E) A patient with a concomitant ethanol ingestion

2-E. The major adverse effect of flumazenil is seizure activity. It is therefore contraindicated in patients who are on benzodiazepine therapy for seizure prophylaxis, such as phenobarbital, and in those patients who chronically use or abuse benzodiazepines for their anxiolytic effect. Flumazenil also is contraindicated in mixed ingestions of benzodiazepines and drugs that are epileptogenic, such as tricyclic antidepressants and antihistamines. Ethanol is not a known epileptogenic toxin and would therefore not promote seizure activity (See section XII E 4).

3. A 25-year-old man is brought to the emergency department (ED) because he was found unconscious. Upon arrival, he is acutely agitated and restless. Physical examination reveals a well-developed male, with fever of 102°F, pulse rate 100 beats per minute (bpm), and blood pressure (BP) of 140/100. His mental status is waxing and waning. His pupils are 2 mm bilaterally, and reactive to light. There is bidirectional nystagmus. He denies any past medical history and admits only to “partying with friends” a few hours earlier. Which of the following agents is the most likely toxin in this scenario?

(A) Cocaine

(B) Crystal methamphetamine



(E) Ethanol

3-C. The most consistent clinical finding in phencyclidine (PCP) intoxication is bidirectional nystagmus. The waxing and waning of mental status also is characteristic of PCP overdose. In cocaine and amphetamine overdose, there is an early peak of euphoria and agitation, after which the patient “crashes.” Note also that the patient's pupil size is 2 mm. If this were a cocaine or amphetamine overdose, you would expect to see mydriasis. The findings of hyperthermia and tachycardia are common to sympathomimetic and PCP overdose; diaphoresis and significant hypertension are more common with sympathomimetics. In terms of mental status, agitation is common to all choices listed. Whereas cocaine and amphetamine toxicity is associated with paranoia and hallucinations, however, LSD toxicity commonly manifests with the patient reporting a feeling of dissociation and the presence of synesthesias. Ethanol intoxication usually is not associated with extreme agitation, fever, or bidirectional nystagmus (See section XIV B).

4. A 20-year-old college student is brought to the emergency department (ED) by her roommate. The patient had been vomiting since the previous evening, following the university provost's luncheon. She took two 10 mg tablets of prochlorperazine. The vomiting has subsided, but she now presents with sustained spasm of the sternocleidomastoid and trapezius muscles, and is unable to turn her head to the left. Her vital signs are within normal limits. Which of the following is the most appropriate treatment at this time?

(A) Observation for 4–6 hours

(B) Diphenhydramine

(C) Diazepam

(D) Ibuprofen

(E) Dantrolene

4-B. This patient is experiencing an acute dystonic reaction, which is an extrapyramidal side effect associated with the phenothiazine class of drugs, to which prochlorperazine belongs. The reaction is a non–dose-related, idiosyncratic one. Treatment consists of 25–50 mg of intravenous diphenhydramine and/or 2 mg of intramuscular benztropine mesylate, so diphenhydramine is the correct answer. Symptoms should resolve within 15–30 minutes after administration of the drug. To prevent recurrence of symptoms once the medication effect has worn off, the patient should be discharged with oral medication to cover the next 72 hours. Observation will only prolong the patient's suffering and anxiety and is therefore inappropriate, although the symptoms probably will resolve eventually without treatment. Diazepam is an anticonvulsant and muscle relaxant. Although it probably would help with the spasm, it is reserved for seizures associated with phenothiazines, whereas simple dystonic reactions are treated with anticholinergics. Ibuprofen is a nonsteroidal anti-inflammatory agent, which may help with pain relief, but is ineffective in reversing the cholinergic effect. Dantrolene is used to treat malignant hyperthermia, which can be seen with phenothiazine overdose (rarely), but is not present in this case (See section XI D 8).

5. A 27-year-old man is brought to the emergency department (ED) by his family because he has been agitated and unable to sleep, and insists there are dung beetles crawling under his skin, when in fact there are none. Physical examination reveals mydriasis, a temperature of 101°F, a pulse rate of 120 beats per minute (bpm), and blood pressure (BP) of 150/110. The patient is diaphoretic and appears to be in acute distress. The family states that the patient does have a history of drug abuse. Which of the following drugs is most likely to produce this reaction?

(A) Heroin

(B) Alcohol

(C) Cocaine

(D) Phenobarbital

(E) Diazepam

5-C. Cocaine and amphetamine overdoses typically result in paranoia. Formication, the feeling that bugs are crawling all over one's skin, also is classically associated with cocaine overdose. Physical findings in cocaine overdose are mydriasis, tachycardia, hypertension, and diaphoresis. The patient usually appears anxious. Heroin (opiate), alcohol, diazepam (benzodiazepine), and phenobarbital (barbiturate) are CNS depressants; therefore, overdose of these would result in a comatose patient, not an acutely agitated one (See section XIII A).

6. A 37-year-old intoxicated man presents to the emergency department (ED) disoriented and staggering. As you undress him to look for signs of trauma, you notice a bottle of antifreeze in his pocket and suspect ethylene glycol toxicity. Which of the following criteria is necessary before antidote therapy can be instituted?

(A) Serum ethylene glycol level of 25 mg/dl

(B) Presence of pulmonary edema

(C) Impending renal failure

(D) Serum pH < 7.2

(E) None of the above

6-E. If ethylene glycol ingestion is suspected, antidote treatment with fomepizole or ethanol is instituted right away. It is not necessary to have any other criteria. Target blood ethanol level is 100–150 mg/dl. A serum ethylene glycol level of 25 mg/dl, pulmonary edema, renal failure, and severe acidosis are criteria for hemodialysis (See section VII E 7).

7. A 72-year-old woman presents to the emergency department (ED) because for the past few hours, she has been experiencing watery eyes, a runny nose, and diarrhea, and states she feels “hot as hell” although it is only 50°F outside. She states she was doing garden work earlier today and may have spilled some garden chemicals on herself. Which of the following is the most likely poison in this case?

(A) Organophosphate insecticide

(B) Atropine

(C) Poisonous mushroom from the garden

(D) Tricyclic antidepressant (TCA) overdose

(E) None of the above

7-A. Given the patient's history, the most likely toxin is an organophosphate or carbamate insecticide. Although there are mushrooms that cause cholinergic toxicity, these would have to be ingested, so that possibility is very unlikely. Atropine ingestion and tricyclic antidepressant (TCA) overdose produce the opposite syndrome of anticholinergic excess and are therefore inappropriate (See section XIX B).

8. For which of the following ingestions is activated charcoal useful?

(A) Hydrocarbons

(B) Lithium

(C) Aspirin

(D) Iron

(E) Mineral acid

8-C. Activated charcoal (AC) is not useful for substances that will not bind to it, including lithium, iron, bromides, hydrocarbons, borates, and mineral acids and alkali. However, AC is appropriate in any ingestion where it is not otherwise contraindicated (e.g., caustic or corrosive ingestions) (See section I H 2).

9. Which of the following drugs is the drug of choice for treating ventricular dysrhythmias in tricyclic antidepressant (TCA) overdose?

(A) Flecainide

(B) Procainamide

(C) Sodium bicarbonate

(D) Flumazenil

(E) Physostigmine

9-C. Because tricyclic antidepressants (TCAs) are, themselves, class Ia antiarrhythmics, other class I (a, b, or c) agents such as procainamide (Ia) and flecainide (Ic) would only potentiate the effect, and are, therefore, contraindicated. Flumazenil is a benzodiazepine antagonist. Its use is contraindicated in ingestions involving TCAs, because they can contribute to the epileptogenic potential of flumazenil. Finally, physostigmine is contraindicated in the treatment of anticholinergic symptoms associated with TCA overdose, again due to the potential for inducing seizures. Although other drugs such as lidocaine and bretylium can be used to treat TCA-induced dysrhythmias, sodium bicarbonate remains the drug of choice, and is effective for most ECG abnormalities (See section IX D 3).

10. Which of the following is an important cofactor administered to detoxify formate in the treatment of methanol poisoning?

(A) Pyridoxine

(B) Folic acid

(C) Vitamin B12s

(D) Thiamine

(E) Vitamin C

10-B. Pyridoxine and thiamine are cofactors administered in the treatment of ethylene glycol poisoning. Vitamin B12 is administered in megaloblastic anemia, not for methanol poisoning. Vitamin C is an important cofactor in the production of collagen, but is irrelevant here (See section VIII E 4).

11. Which of the following drugs is the mainstay in the treatment of cocaine overdose?

(A) A benzodiazepine such as diazepam

(B) A barbiturate such as phenobarbital

(C) A β-blocker such as propranolol

(D) An antipsychotic such as haloperidol

(E) A tricyclic antidepressant such as imipramine

11-A. The drug of choice for cocaine overdose is a benzodiazepine, which counters the anxiety, agitation, hypertension, hyperthermia, and seizures associated with cocaine toxicity. There is no role for the use of barbiturates or tricyclic antidepressants in cocaine overdose. β-blockers and haloperidol can be used, but they are second-line agents to benzodiazepines (See section XIII D 1).

12. What is the most common coingestant in adult drug overdoses?

(A) A benzodiazepine

(B) An antidepressant

(C) A sympathomimetic

(D) Ethanol

(E) A household cleaner

12-D. Ethanol is the most common coingestant in adult drug overdoses. This must be kept in mind, because ethanol may mask or exacerbate toxicity of the other drug(s) ingested (See section I D 5).

13. For which one of the following ingestions is abdominal radiograph useful?

(A) Aspirin

(B) Methadone

(C) Meperidine

(D) Acetaminophen

(E) Diazepam

13-A. An abdominal radiograph can detect radiopaque pill fragments, so it is useful for detecting aspirin ingestion. Common radiopaque substances seen in overdoses are summarized by the acronym CHIPES: chloral hydrate, heavy metals, iron, isoniazid, psychotropics (TCAs), phenothiazines, potassium, enteric-coated preparations, salicylates, and salts (See section I G 4).