Clinical Toxicology

Definitions 1. Clinical toxicology: Focuses on the eff ects of substances in patients caused by accidental poisonings or intentional overdoses of medications, drugs of abuse, household products, or various other chemicals 2. Intoxication: Toxicity associated with any chemical substance 3. Poisoning: A clinical toxicity secondary to accidental exposure 4. Overdose: An intentional exposure with the intent of causing self-injury or death 5. Toxidromes: A group of signs, symptoms, and laboratory findings that suggest a specific ingestion

General Management

A. Supportive care and ABCs: Evaluating and supporting the vital functions (airway, breathing, and circulation [ABCs]) are the mandatory first steps in the initial management of drug ingestions. After the patient is stabilized, the specific issue(s) of poison management should be addressed.

B. Treatment for patients with depressed mental status includes the following: 1. To rule out or treat hypoglycemia, 50 mL of 50% dextrose in adults and 1 mL/kg in children intravenously (IV). 2. Thiamine 100 mg IV push (glucose can precipitate the Wernicke-Korsakoff syndrome in thiamine-deficient patients). 3. Naloxone (Narcan) 0.4 to 2 mg IV push, if opiate ingestion is suspected. Naloxone may also be administered by the following routes: inhalation, intramuscular, and intranasal.

C. Obtaining a history of exposure 1. Identify the substance(s) ingested, the route of exposure, the quantity ingested, the amount of time since ingestion, signs and symptoms of overdose, and any associated illness or injury. Corroborate history and other physical evidence (e.g., pill containers) from prehospital providers. 2. Neurological examination evaluates any seizures, alterations in consciousness, confusion, ataxia, slurred speech, tremor, headache, or syncope. 3. Cardiopulmonary examination evaluates any syncope, palpitations, cough, chest pain, shortness of breath, or

5. Past medical history should include a. Medications, including nonprescription (over-the-counter [OTC]) substances b. Use of herbal medications c. Alcohol or drug abuse d. Psychiatric history e. Allergies f. Occupational or hobby exposures g. Travel h. Prior ingestions i. Social history with potential for domestic violence or

D. Routine laboratory assessment 1. Complete blood cell (CBC) count 2. Serum electrolytes 3. Blood urea nitrogen (BUN); serum creatinine (SCr) 4. Blood glucose 5. Urinalysis 6. Electrocardiogram (ECG) 7. Chest roentgenogram and/or kidneys, ureters, and bladder (KUB) x-ray

E. Toxicology laboratory tests 1. Advantages a. Confirm or determine the presence of a particular agent b. Predict the anticipated toxic eff ects or severity of exposure to some poisons c. Confirm or distinguish diff erential or contributing diagnosis d. Occasionally help guide therapy

2. Disadvantages a. These tests cannot provide a specifi c diagnosis for all patients. b. All possible intoxicating agents cannot be screened. c. In critically ill patients, supportive treatment is needed before laboratory results of the toxicology screen are available. d. Laboratory drug-detection abilities differ. e. In general, only a qualitative determination of a substance or substances is necessary; however, quantitative levels of the therapeutically monitored drugs may be necessary to guide therapy. Consult with your local laboratory for the availability of specific drug assays.

F. Skin decontamination should be performed when percutaneous absorption of a substance may result in systemic toxicity, or when the contaminating substance may produce local toxic effects (e.g., acid burns). The patient’s clothing is removed, and the areas are irrigated with copious quantities of water. Neutralization should not be attempted. For example, neutralizing acid burns with sodium bicarbonate will produce an exothermic chemical reaction, thereby exacerbating the patient’s condition.

G. Gastric decontamination may be attempted when supportive care is begun. GI decontamination involves removal of the ingestant with emesis or lavage, the use of activated charcoal potentially to bind any ingestants, and the use of cathartics to hasten excretion and thereby limit absorption.

1. Emesis a. Contraindications (1) Children younger than 6 months of age (2) Patients with central nervous system (CNS) depression or seizures (3) Patients who have ingested a strong acid, alkali, or a sharp object (4) Patients with compromised airway protective reflexes (including coma and convulsions) (5) Patients who have ingested some types of hydrocarbons or petroleum distillates (6) Patients who have ingested substances with an extremely rapid onset of action (7) Patients with emesis after the ingestion

b. Syrup of ipecac: Owing to concerns of safety, efficacy, and the delay of antidote administration, syrup of ipecac is no longer recommended for general use. Ipecac may be administered within 30 mins of ingestion and only on the advice of a poison control center.

2. Gastric lavage a. Use: Gastric lavage is infrequently used in patients who are not alert or have a diminished gag reflex. This procedure should also be considered in patients who are seen early after massive ingestions. This procedure is contraindicated in patients who have ingested acids, alkalis, or hydrocarbons. In addition, patients should not receive gastric lavage if they are at risk for GI perforation or if they are combative.

3. Activated charcoal adsorbs almost all commonly ingested drugs and chemicals and is usually administered to most overdose patients as quickly as possible (ideally, within 1 hr of ingestion). Commonly ingested substances not adsorbed include ethanol, iron, lithium, cyanide, ethylene glycol, lead, mercury, methanol, organic solvents, potassium, strong acids, and strong alkalis. a. Dosage: Activated charcoal (Actidose with sorbitol) is available as a colloidal dispersion with water or sorbitol. In adults, the dose of activated charcoal is 25 to 100 g; the dose in children1 to 12 years of age is 25 to 50 g; the dose in

Constipation has not been observed after the administration of a single dose of activated charcoal. Multiple doses of any cathartics should be avoided because they can cause electrolyte imbalances and/or dehydration. Toxic ingestions with drugs having an enterohepatic circulation (e.g., carbamazepine, theophylline, phenobarbital, tricyclic antidepressants, phenothiazines, digitalis) generally require that the charcoal be readministered every 6 hrs to prevent reabsorption during recirculation.

b. Adverse effects: Charcoal aspiration and empyema have been reported in the literature. As such, charcoal should be withheld if patients are vomiting. Bowel obstruction may occur with multiple doses of activated charcoal and/or patients who are receiving concomitant therapy with neuromuscular-blocking drugs.

H. Whole bowel irrigation has been shown to be effective under certain conditions, particularly when activated charcoal lacks efficacy. An isosmotic cathartic solution such as polyethylene glycol (GoLYTELY, Colyte) is used. The dosage is 1 to 2 L/hr given orally or by nasogastric tube until the rectal effluent is clear.

Forced diuresis and urinary pH manipulation may be used to enhance the elimination of substances, whose elimination is primarily renal, if the substance has a relatively small volume of distribution with little protein binding. However, the use of these methods is associated with fluid and electrolyte disturbances. Alkaline diuresis promotes the ionization of weak acids, thereby preventing their reabsorption by the kidney, which facilitates the excretion of such weak acids. This procedure has been used in the management of patients who have ingested long-acting barbiturates such as phenobarbital or salicylic acid. Patients are given 50 to 100 mEq of sodium bicarbonate IV push, followed by a continuous infusion of 50 to 100 mEq of sodium bicarbonate in 1 L of 0.25% to 0.45% normal saline, maintaining a urine pH of 7.3 to 8.5. Urine output should be 5 to 7 mL/kg/hr. Complications include metabolic alkalosis, hypernatremia, hyperosmolarity, and fluid overload.

J. Dialysis: In patients who fail to respond to the measures of decontamination already outlined, hemodialysis, and to a lesser extent peritoneal dialysis, may enhance drug elimination. Substances that are removed by hemodialysis generally are water soluble, have a small volume of distribution ( 0.5 L/kg), have a low molecular weight ( 500 Da), and are not significantly bound to plasma proteins. Hemodialysis usually is indicated for life-threatening ingestions of ethylene glycol, methanol, or paraquat. This technique also has been used to enhance the elimination of ethanol, theophylline, lithium, salicylates, and long-acting barbiturates.

K. Hemoperfusion is a technique in which anticoagulated blood is passed through (perfused) a column containing activated charcoal or resin particles. This method of elimination clears substances from the blood more rapidly than hemodialysis, but it does not correct fluid and electrolyte abnormalities as does hemodialysis. Hemoperfusion, although more effective in removing phenobarbital, phenytoin, carbamazepine, methotrexate, and theophylline than hemodialysis, is less eff ective in removing ethanol or methanol. Complications of hemoperfusion include thrombocytopenia, leukopenia, hypocalcemia, hypoglycemia, and hypotension.

III. MANAGEMENT OF SPECIFIC INGESTIONS A. Acetaminophen (Tylenol) is an antipyretic-analgesic that can produce fatal hepatotoxicity in untreated patients through the generation of a toxic metabolite. 1. Available dosage forms: Acetaminophen is available in a variety of OTC and prescription drug products. 2. Toxicokinetics: Acetaminophen is well absorbed from the GI tract and has a half-life between 2 and 3 hrs. Less than 5% is excreted unchanged in the urine; the remainder is metabolized in the liver by the cytochrome P450 system.

3. Clinical presentation a. Phase I (12 to 24 hrs postingestion). Nausea, vomiting, anorexia, and diaphoresis b. Phase II (1 to 4 days postingestion). Asymptomatic c. Phase III (2 to 3 days in untreated patients). Nausea, abdominal pain, progressive evidence of hepatic failure, coma, and death.

4. Laboratory data a. Serum acetaminophen levels: Patients with levels greater than 150, 70, or 40 mg/mL at 4, 8, or 12 hrs after ingestion require antidotal therapy with N-acetylcysteine (NAC) according to the Rumack-Matthews nomogram. b. Baseline liver function tests should be done in all patients. c. Renal function tests, including a BUN and SCr, should be done. d. Coagulation studies include prothrombin time (PT), partial thromboplastin time (PTT), and bleeding time.

5. Treatment a. Adult patients who have ingested 10 g or children who have ingested 200 mg/kg require treatment. Elderly and alcoholic patients have an increased susceptibility to acetaminophen hepatotoxicity. b. The recommended treatment is GI decontamination with activated charcoal. c. Antidotal therapy with NAC is indicated for patients with toxic blood levels of acetaminophen. (1) NAC dosage is 140 mg/kg as a loading dose followed by 70 mg/kg every 4 hrs for a total of 17 doses. NAC is administered either orally or via a nasogastric tube. NAC (Mucomyst) 20%

Each dose must be diluted 1:3 in either cola or fruit juice to mask the unpleasant taste and smell. The dose of NAC should be repeated if the patient vomits within 30 mins of administration. Patients with severe nausea secondary to NAC may be pretreated with IV metoclopramide (Reglan) 10 mg every 6 hrs. Metoclopramide acts as an antiemetic while increasing the rate of NAC absorption. (2) IV NAC (Acetadote) (a) Loading dose: 150 mg/kg over 60 mins (b) Maintenance dose: 50 mg/kg over 4 hrs followed by 100 mg/kg over 16 hrs (c) Anaphylactoid reactions are observed in approximately 20% of patients. Caution should be exercised in patients with a history of asthma.

B. Alcohols 1. Ethylene glycol a. Available forms: Ethylene glycol commonly is used in antifreeze and windshield de-icing solutions. This form is sometimes colorless and has a sweet taste. b. Toxicokinetics: Ethylene glycol is hepatically metabolized by alcohol dehydrogenase to glycolaldehyde,which is metabolized by aldehyde dehydrogenase to glycolic acid. Glycolic acid is converted to glyoxylic acid, whose most toxic metabolite is oxalic acid.

c. Clinical presentation (1) Stage I (0.5 to 12 hrs postingestion). Ataxia, nystagmus, nausea and vomiting, decreased deep tendon reflexes, and severe acidosis (more severe overdoses: hypocalcemic tetany and seizures, cerebral edema, coma, and death) (2) Stage II (12 to 24 hrs postingestion). Tachypnea, cyanosis, tachycardia, pulmonary edema, and pneumonitis (3) Stage III (24 to 72 hrs postingestion). Flank pain and costovertebral angle tenderness; oliguric renal failure d. Laboratory data may reveal severe metabolic acidosis, hypocalcemia, and calcium oxalate crystals in the urinalysis.

e. Treatment (1) Gastric lavage is performed within 30 mins of ingestion. (2) IV ethanol (EtOH) is used in situations in which fomepizole is not available. (a) Indications include an ethylene glycol level 20 mg/dL, suspicion of ingestion pending level, or an anion gap metabolic acidosis with a history of ingestion, regardless of the level. (b) EtOH dosage (i) An EtOH level of at least 100 mg/dL should be maintained. (ii) Loading dose is 7.5 to 10 mL/kg of a 10% ethanol in dextrose 5% in water (D5W) over 1 hr, followed by a maintenance infusion

(3) Fomepizole (Antizol) is a potent inhibitor of alcohol dehydrogenase that can prevent the formation of the toxic metabolites of either methanol or ethylene glycol. (a) Administer a loading dose of 15 mg/kg (up to 1 g) in 100 mL of D5W or 0.9% sodium chloride (NaCl) infused over 30 mins. (b) Maintenance doses: 10 mg/kg every 14 hrs for four doses, then increase to 15 mg/kg (to off set autoinduction phenomenon) until methanol or ethylene glycol levels are 20 mg/dL.

(4) Pyridoxine (100 mg IV every day) and thiamine (100 mg IV every day) are cofactors that may convert glyoxylic acid to nonoxalate metabolites. (5) Sodium bicarbonate is used as needed to correct the acidosis. (6) Hemodialysis Fomepizole must be continued, and the rate of administration may need to be increased. Indications include ethylene glycol level 50 mg/dL, congestive heart failure, renal failure, and severe acidosis.

2. Methanol a. Available forms include gas-line antifreeze, windshield washer, and some sterno. b. Toxicokinetics: Alcohol dehydrogenase converts methanol to formaldehyde, which is then converted to formic acid. c. Clinical presentation (1) Stage I. Euphoria, gregariousness, and muscle weakness for 6 to 36 hrs, depending on the rate of formation of formic acid (2) Stage II. Vomiting, upper abdominal pain, diarrhea, dizziness, headache, restlessness, dyspnea, blurred vision, photophobia, blindness, coma, cerebral edema, cardiac and

e. Treatment (1) Gastric lavage. Charcoal has not been shown to absorb alcohols. (2) IV EtOH (used in situations in which fomepizole is not available) (a) Indications include any peak methanol level 20 mg/dL, a suspicious ingestion with a positive history, or any symptomatic patient with an anion gap acidosis. (b) Administration is the same as per ethylene glycol (see III.B.1). (3) Folic acid administered at 1 mg/kg (maximum 50 mg) IV every 4 hrs for six doses increases the metabolism of formate. (4) Fomepizole (Antizol) (5) Sodium bicarbonate is used for severe acidosis. (6) Hemodialysis is used for methanol levels 50 mg/dL, severe and resistant acidosis, renal failure, or visual symptoms.

C. Anticoagulants 1. Heparin/Low-Molecular-Weight Heparin (LMWH) a. Available dosage forms include parenteral dosage forms for IV and subcutaneous administration. b. Toxicokinetics. Heparin has a half-life of 1 to 1.5 hrs and is primarily metabolized in the liver. The newer LMWHs— enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep)—have a longer half-life, especially in patients with renal failure. c. Clinical presentation. Look for any signs or symptoms of bleeding or bruising.

e. Treatment (1) Stopping heparin administration for 1 to 2 hrs and restarting therapy at a reduced dose can reverse mild over-anticoagulation. (2) Severe overdoses may require the administration of protamine. (a) Protamine combines with heparin and neutralizes it: 1 mg protamine neutralizes 100 U heparin. (b) Protamine should be administered slowly, intravenously over 10 mins. The maximum dose of protamine is 50 mg in any 10-min period.

(c) Considerable controversy exists about the method of reversing the over-anticoagulation with LMWHs. Some sources recommend the administration of protamine to neutralize part of the effects of these anticoagulants, whereas case reports reported successes with recombinant factor VII (NovoSeven). (d) These overdoses should be referred to a hematologist and/or the poison control center

2. Warfarin (Coumadin) a. Available dosage forms include oral tablets and a solution for parenteral administration. b. Toxicokinetics. Warfarin is well absorbed after oral administration. Its mean half-life is 35 hrs; protein binding is 99%, with 5-day duration of activity. Vitamin K-dependent clotting factors begin to decline 6 hrs after administration, but therapeutic anticoagulation may require several days. c. Clinical presentation includes minor bleeding, bruising, hematuria, epistaxis, and conjunctival hemorrhage. More serious bleeding includes GI, intracranial, retroperitoneal, and wound site. d. Laboratory data include PT, international normalized ratio (INR), and bleeding time.

e. Treatment (1) If PT or INR is slightly elevated, withhold warfarin for 24 to 48 hrs, then reinstitute therapy with a reduced dosage. (2) If PT or INR is elevated and bleeding, administer 10 mg of phytonadione (vitamin K) over 30 mins. Patients who are bleeding may require the administration of blood products that contain clotting factors. (3) For mild over-anticoagulation, follow American College of Chest Physicians (ACCP) guidelines. (4) For patients with life-threatening bleeding or intracranial

3. Pradaxa (dabigatran) a. Available dosage forms include oral capsules. b. Toxicokinetics. Dabigatran is poorly absorbed following oral administration, but it has a half life of 12 to 17 hrs in healthy subjects with normal renal function. c. Clinical presentation includes minor bleeding, bruising, hematuria, and epistaxis. More serious bleeding includes GI, intracranial, retroperitoneal, and wound site. d. Laboratory data specialized hematologic monitoring may be required such as thrombin clotting time and ecarin clotting time.

e. Treatment (1) Mild bleeding. Local treatment and withholding one dose (2) Moderate bleeding. Consider blood product transfusion and/or hemodialysis (3) Severe bleeding. As noted earlier with the additional consideration of charcoal filtration along with either recombinant factor VII or prothrombin complex concentrates. Dabigatran is the fi rst FDA-approved oral direct-acting thrombin inhibitor. Many more compounds are in clinical trials and due to the paucity of overdose data with these drugs, consultation with a hematologist and/or a poison information specialist is highly recommended

D. Antidepressants 1. Tricyclic antidepressants (TCAs) a. Available forms include amitriptyline (Elavil), nortriptyline (Aventyl), imipramine (Tofranil), desipramine (Norpramin), doxepin (Sinequan), protriptyline (Vivactil), and clomipramine (Anafranil). b. Toxicokinetics. The compounds are hepatically metabolized, undergo enterohepatic recirculation, are highly bound to plasma proteins, and have an elimination half-life of approximately 24 hrs.

c. Clinical presentation. Anticholinergic eff ects include mydriasis, ileus, urinary retention, and hyperpyrexia. Cardiopulmonary toxicity exhibits tachycardias, conduction blocks, hypotension, and pulmonary edema. CNS manifestations range from agitation and confusion to hallucinations, seizures, and coma. d. Laboratory data. Blood level monitoring does not correlate well with clinical signs and symptoms of toxicity. Some authors suggest that electrocardiographic monitoring is a better guide to assessing the severity of ingestion.

e. Treatment (1) GI decontamination. Syrup of ipecac is not recommended because patients may quickly become comatose, increasing the risk of aspiration. Activated charcoal is given every 6 hrs. (2) Alkalinization with sodium bicarbonate 1 to 2 mEq/kg to maintain an arterial pH of 7.45 to 7.55 decreases the free fraction of the absorbed toxins, while reversing some of the cardiac abnormalities. (3) Phenytoin (Dilantin) and/or benzodiazepines may be required to control seizures. Phenytoin must be administered at a rate not exceeding 25 mg/min because of hypotensive side effects. (Fosphenytoin [Cerebyx] may be used because it has a lower incidence of hypotension than phenytoin.) (4) Physostigmine 2 mg IV over 1 min may be used to reverse severe anticholinergic toxicity owing to these drugs. Because this antidote may cause asystole, the use of this antidote for TCA overdoses is declining.

2. Selective serotonin reuptake inhibitors (SSRIs) a. Available forms (nontricyclic agents) include fl uoxetine (Prozac), sertraline (Zoloft ), and paroxetine (Paxil). b. Toxicokinetics. SSRIs are well absorbed aft eroral administration. Peak levels occur within 2 to 6 hrs. SSRIs are hepatically metabolized with a half-life between 8 and 30 hrs. c. Clinical presentation includes mild symptomatology. Patients may become agitated, drowsy, or confused. Seizures and cardiovascular toxicity are rare. d. Laboratory data. ECG monitoring is recommended. Blood level monitoring is not recommended.

E. Benzodiazepines 1. Available forms include chlordiazepoxide (Librium), diazepam (Valium), fl urazepam (Dalmane), midazolam (Versed), lorazepam (Ativan), alprazolam (Xanax), and triazolam (Halcion). 2. Toxicokinetics. These drugs are hepatically metabolized. 3. Clinical presentation includes drowsiness, ataxia, and confusion. Fatalities are rare. 4. Laboratory data. Drug level monitoring is not indicated.

5. Treatment a. Supportive treatment includes gastric emptying, activated charcoal, and a cathartic. b. Flumazenil (Romazicon) is given 0.2 mg IV over 30 secs; repeat doses of 0.5 mg over 30 secs at 1-min intervals for a maximum cumulative dose of 5 mg. (1) Flumazenil has a short elimination half-life. (2) Careful observation for resedation is necessary, especially for ingestions of long-acting benzodiazepines. (3) Flumazenil is contraindicated in mixed overdose patients (particularly involving tricyclic antidepressants) in whom seizures are likely.

F. -adrenergic antagonists 1. Available dosage forms. Class examples include propranolol (Inderal), metoprolol (Lopressor), and atenolol (Tenormin). Oral and parenteral dosage forms are available. 2. Toxicokinetics. All of the members within this class differ in regard to renal versus hepatic elimination, lipid solubility, and protein binding. Patients may become toxic owing to changes in organ function. 3. Clinical presentation includes hypotension, bradycardia, and atrioventricular block. Bronchospasm may occur, particularly with noncardioselective agents. 4. Laboratory data include serum electrolytes and blood

5. Treatment a. GI decontamination includes gastric lavage and activated charcoal. b. Glucagon is given 50 to 150 mcg/kg as a loading dose over 1 min, followed by a continuous infusion of 1 to 5 mg/hr. c. Epinephrine should be used cautiously in -blocker overdoses. Unopposed -receptor stimulation in the face of complete -receptor block may lead to profound hypertension. d. Calcium salts (see “Calcium Channel Antagonists”) e. High-dose insulin dextrose (see “Calcium Channel Antagonists”)

G. Calcium channel antagonists 1. Available forms include verapamil (Calan), diltiazem (Cardizem), and the dihydropyridine class (nifedipine derivatives [Procardia]). 2. Toxicokinetics. Onset of action is approximately 30 mins, whereas the duration is 6 to 8 hrs. Several compounds are available as sustained-release dosage forms, which may contribute to prolonged toxicity. 3. Clinical presentation. Hypotension is common to all classes. Bradycardia and atrioventricular block are more commonly seen with ingestions of verapamil or diltiazem. Pulmonary edema and seizures (verapamil) have been

5. Treatment a. GI decontamination includes gastric lavage, activated charcoal, and whole-bowel irrigation (especially for ingestions with sustained-release products). b. Calcium. Calcium chloride 10% (10 to 20 mL) IV push is given for the management of hypotension, bradycardia, or heart block. c. Glucagon dosage is the same as for -blocker overdose. d. Combined insulin and dextrose administration has been used in selected cases. The insulin dosages used are as follows: regular insulin 1 U/kg and a loading dose along with IV dextrose 0.5 g/kg. This should be followed with a continuous infusion of insulin at a rate of 0.5 to 2 U/kg/hr along with continuous dextrose infusions of 0.5 g/kg/hr to maintain serum glucose levels within a 100 to 250 mg/dL range. Insulin dosages are titrated to appropriate hemodynamic indices in an intensive care environment. This should be used only in consultation with a poison

H. Cocaine 1. Available forms include alkaloid obtained from Erythroxylon coca. 2. Toxicokinetics. Cocaine is well absorbed aft er oral, inhalational, intranasal, and IV administration. Cocaine is metabolized in the liver and excreted in the urine. 3. Clinical presentation includes CNS and sympathetic stimulation (e.g., hypertension, tachypnea, tachycardia, nausea, vomiting, seizures). Death may result from respiratory failure, myocardial infarction, or cardiac arrest. 4. Laboratory data include cocaine and cocaine metabolite urine screens.

I. Corrosives 1. Available forms include strong acids or alkalis. 2. Toxicokinetics. Corrosives are well absorbed aft er oral and inhalational administration. 3. Clinical presentation. These compounds produce burns on contact. 4. Laboratory data. Arterial blood gases (ABGs), chest radiographs, and at least 6 hrs of observation are required for inhalation exposure. 5. Treatment is decontamination. Exposed skin must be irrigated with water. Neutralization should be avoided because these reactions are exothermic and will produce

J. Cyanide 1. Available forms include industrial chemicals and some nail polish removers. 2. Toxicokinetics. Th e drug is rapidly absorbed aft er oral or inhalation exposure. 3. Clinical presentation includes headache, dyspnea, nausea, vomiting, ataxia, coma, seizures, and death. 4. Laboratory data include cyanide levels, ABGs, electrolytes, and an ECG.

5. Treatment a. Cyanide antidote kit (1) Amyl nitrite. Pearls are crushed and held under the patient’s nostrils. (2) Sodium nitrite 10 mL IV push. Converts hemoglobin to methemoglobin, which binds the cyanide ion. (3) Sodium thiosulfate 50 mL of a 25% solution IV push. May be repeated if there is no response. b. Oxygen c. Sodium bicarbonate. As needed for severe acidosis d. Hydroxocobalamin (Cyanokit) adult dose is 5 g IV over 15 mins. Dose may be repeated for a total dose of 10 g. No data

K. Digoxin (Lanoxin) 1. Available dosage forms include oral and parenteral. 2. Toxicokinetics. Digoxin is well absorbed, is primarily renally eliminated, and has a half-life of 36 to 48 hrs. Its volume of distribution is 7 to 10 L/kg. Equilibration between serum level and myocardial binding requires 6 to 8 hrs. 3. Clinical presentation includes confusion, anorexia, nausea, and vomiting in mild cases. In more severe cases, cardiac dysrhythmias are seen. 4. Laboratory data include serum digoxin levels, electrolytes, particularly serum potassium levels, and an ECG.

5. Treatment a. Decontamination with activated charcoal is recommended. b. Supportive therapy includes managing hyperkalemia or hypokalemia and inotropic support as needed. c. Digoxin-specifi c Fab antibodies (Digibind). To determine the dosage, use the following formula: Dose (mg) [(serum digoxin concentration [ng/mL] weight (kg)/100]) (mg/vial) Digibind 38 mg/vial or Digifab 40 mg/vial

L. Electrolytes 1. Magnesium a. Available dosage forms include oral, rectal, and parenteral. Magnesium-containing cathartics (e.g., magnesium citrate) have been reported to produce hypermagnesemia in patients receiving repetitive doses with activated charcoal. b. Toxicokinetics. Magnesium is found intracellularly and is renally eliminated. c. Clinical presentation (1) Mild. Deep tendon refl exes may be depressed; lethargy and weakness

d. Laboratory data (1) Mild: 4 mEq/L (2) Severe: 10 mEq/L e. Treatment is 10% calcium chloride 10 to 20 mL to temporarily antagonize the cardiac effects of magnesium. In severe cases, hemodialysis may be required.

2. Potassium a. Available dosage forms are oral and parenteral. b. Toxicokinetics. Potassium is primarily an intracellular cation. Changes in acid–base balance produce shift s in serum potassium values (e.g., a 0.1 U increase in serum pH produces a 0.1 to 0.7 mEq/L decrease in serum potassium values). c. Clinical presentation includes cardiac irritability and peripheral weakness with minor increases. Cardiac dysrhythmias, including bradycardia, may progress to asystole. d. Laboratory data. ECG data include peaked T waves and prolongation of the QRS complex.

e. Treatment (1) Calcium. Administer calcium chloride 10% 10 to 20 mL to antagonize the cardiac effects of hyperkalemia. (2) Sodium bicarbonate. 1 to 2 mEq/kg IV increases serum pH and causes an intracellular shift of potassium. (3) Glucose and insulin. 50 mL of 50% dextrose and 5 to 10 U of regular insulin are administered via IV push to shift potassium from the extracellular fl uid into the cells.

(4) Cation exchange resins bind potassium in exchange for another cation (sodium). Sodium polystyrene sulfonate (Kayexalate) is given 15 g/60 mL with 23.5% sorbitol in doses 15 to 30 g by mouth every 3 to 4 hrs as needed until the hyperkalemia resolves. Alternatively, 50 g of sodium polystyrene sulfonate can be given rectally in 200 mL of sodium chloride as a retention enema. Th ere have been reports of colonic necrosis and other GI events. Some authors recommend other treatments before utilizing exchange resin therapy. (5) Hemodialysis is reserved for life-threatening hyperkalemia that does not respond to the aforementioned measures.

M. Iron (Fe) 1. Available dosage forms. Numerous OTC products are available. Toxicity is based on the amount of elemental iron ingested: sulfate salt 20% elemental Fe; fumarate salt 33% elemental Fe; and gluconate salt 12% elemental Fe. 2. Toxicokinetics. Iron is absorbed in the duodenum and jejunum. 3. Clinical presentation a. Phase I. Nausea, vomiting, diarrhea, GI bleeding, hypotension b. Phase II. Clinical improvement seen 6 to 24 hrs postingestion

4. Laboratory data include serum Fe levels, total ironbinding capacity (TIBC; is controversial), ABGs, liver function tests (LFTs), hemoglobin, and hematocrit. Radiological evaluation of the abdomen notes the presence of radiopaque pills. 5. Treatment a. Decontamination. For ingestions 40 mg/kg. Gastric lavage using sodium bicarbonate is of questionable efficacy. Whole-bowel irrigation is used for large ingestions. b. Supportive treatment c. Deferoxamine (Desferal) is used to chelate iron. Administer at a rate of 15 mg/kg/hr up to a maximum dose of

N. Isoniazid (INH) 1. Available dosage forms include oral and parenteral. 2. Toxicokinetics. INH is well absorbed orally. Peak levels are within 1 to 2 hrs postingestion. Isoniazid is hepatically metabolized. 3. Clinical presentation includes nausea, vomiting, slurred speech, ataxia, generalized tonic–clonic seizures, and coma. 4. Laboratory data include severe lactic acidosis, hypoglycemia, mild hyperkalemia, and leukocytosis.

5. Treatment a. Decontamination. Avoid emesis because patients are at high risk for developing seizures; for severe ingestions, use activated charcoal gastric lavage. b. Pyridoxine, which reverses INH-induced seizures, is given in gram doses equivalent to the amount of isoniazid ingested. Pyridoxine is mixed as a 10% solution in D5W and infused at 0.5 g/min until seizures stop, with the remainder infused over 4 to 6 hrs (maximum adult dose: 5 g). c. Sodium bicarbonate corrects the acidosis.

O. Lead 1. Available forms include lead-containing paint or gasoline fume inhalation. 2. Toxicokinetics. Lead has slow distribution, with a half-life of approximately 2 months. 3. Clinical presentation includes nausea, vomiting, abdominal pain, peripheral neuropathies, convulsions, and coma. 4. Laboratory data include anemia and an elevated bloodlead level.

5. Treatment a. Edetate calcium disodium (Calcium Disodium Versenate) is given 50 to 75 mg/kg/day intramuscularly (IM) or via slow IV in four divided doses. b. Dimercaprol (BAL) is given 4 mg/kg IM every 4 hrs for 3 to 5 days. Dimercaprol therapy is administered fi rst. Following the second dose, concomitant edetate calcium disodium is initiated and both therapies are continued for up to 5 days. Oral chelation therapy is used for less severe cases.

P. Lithium (Eskalith) 1. Available dosage forms include liquid, capsules, and tablets (immediate and sustained release). 2. Toxicokinetics. Lithium is well absorbed aft er oral administration. It is not appreciably bound to plasma proteins and has a small volume of distribution (Vd) of 0.5 L/kg. Elimination is renal, with a half-life of 14 to 24 hrs. 3. Clinical presentation a. Mild. Polyuria, blurred vision, weakness, slurred speech, ataxia, tremor, and myoclonic jerks

5. Treatment a. Supportive care, including basic life support and fl uid and electrolyte replacement b. Decontamination (1) Syrup of ipecac not recommended (2) Activated charcoal ineffective (3) Sodium polystyrene sulfonate has been eff ective in experimental models. Need to monitor potassium levels. (4) Whole-bowel irrigation for large ingestions, especially those involving sustained-release products (5) Hemodialysis for severely symptomatic patients with acute exposure levels 2.5 mEq/L or chronic levels 1.5 mEq/L. Note: Lithium levels may rise aft er dialysis owing to a rebound eff ect.

Q. Opiates 1. Available dosage forms include oral immediate-release and sustained-release preparations as well as parenteral agents. 2. Toxicokinetics. Some agents have prolonged elimination half-lives (e.g., heroin, methadone). 3. Clinical presentation includes respiratory depression and a decreased level of consciousness.Rare effects include hypotension, bradycardia, and pulmonary edema. Seizures have been reported in patients with renal dysfunction in individuals who are receiving meperidine owing to the accumulation of the metabolite or meperidine.

5. Treatment a. Naloxone is given 0.4 to 2.0 mg every 5 mins up to 10 mg and 0.03 to 0.1 mg/kg in pediatric patients. Naloxone has a very short half-life, and resedation is a concern in patients overdosing on long-acting opioids or sustained-release dosage forms. b. Nalmefene (Revex) has a half-life of 4 to 8 hrs. Initial dosages are 0.5 mg/70 kg. A follow-up dose 2 to 5 mins later is 1 mg/70 kg.

R. Organophosphates 1. There are several available forms; they are usually pesticides or chemical warfare agents. 2. Toxicokinetics. Organophosphates are absorbed through the lungs, skin, GI tract, and conjunctiva. 3. Clinical presentation includes excessive cholinergic stimulation. 4. Laboratory data include red blood cell acetylcholinesterase activity. 5. Treatment a. Decontamination b. Atropine is given 0.5 to 2.0 mg IV to reverse the

S. Salicylates 1. Available dosage forms include several OTC products: oral, rectal, and topical. 2. Toxicokinetics. Salicylates are well absorbed aft er oral administration. The half-life is 6 to 12 hrs at lower doses. In overdose situations, the half-life may be prolonged to more than 20 hrs. 3. Clinical presentation includes nausea, vomiting, tinnitus,

4. Laboratory data for the following 6-hr postingestion levels are: a. 40 to 60 mg/dL: tinnitus b. 60 to 95 mg/dL: moderate toxicity c. More than 95 mg/dL: severe toxicity d. With the presence of acidemia and aciduria, evaluate ABGs. e. In addition, laboratory evaluation may show leukocytosis, thrombocytopenia, increased or decreased serum glucose and sodium, hypokalemia, and increased serum BUN, creatinine, and ketones.

5. Treatment a. Decontamination. Repetitive doses of activated charcoal every 6 hrs, with one dose of cathartic for patients who ingested 150 mg/kg. Whole-bowel irrigation for large ingestions. b. Alkaline diuresis is given as noted in decontamination section to enhance salicylate excretion.This is indicated for levels 40 mg/dL. c. Hemodialysis is used for severe intoxications when serum levels are 100 mg/dL. This method of decontamination is much better than repetitive doses of activated charcoal.

T. Snake bites 1. Types. There are numerous species of snakes found worldwide. The venomous snakes found in North America include the following: rattlesnake, cottonmouth, copperhead, and coral. Because patients may be exposed to more exotic snakes, a herpetologist should be consulted for a more defi nitive identifi cation. 2. Toxicokinetics. Onset of symptomatology depends on the species of snake and the patient’s underlying medical condition.

4. Laboratory data a. CBC and platelet count b. Coagulation profi le c. Fibrin degradation products d. Electrolytes e. BUN, SCr, and urinalysis

5. Treatment a. Supportive. Move the patient away from striking distance of the snake. Ideally, the patient should be transported to a medical facility as soon as possible. Constrictive clothing, rings, watches, etc. should be removed. Tetanus immunization should be assessed, and surgical intervention may be necessary for severe cases. b. Antivenoms (1) Antivenin (Crotalidae) polyvalent is a horse-derived product that has been reported to produce allergic reactions. For mild bites, the recommended dose is 5 to 10 vials; moderate,10–20; and severe envenomations may require 20

U. Theophylline 1. Available dosage forms include liquid, sustained-release tablets, and capsules as well as parenteral forms. 2. Toxicokinetics. Well absorbed orally with a Vd of approximately 0.5 L/kg. Th eophylline is hepatically metabolized and has a half-life of 4 to 8 hrs. Theophylline clearance depends highly on age, concomitant disease states, and interacting drugs. 3. Clinical presentation includes nausea, vomiting, seizures, and cardiac dysrhythmias. Chronic toxicity carries a poorer

5. Treatment a. Supportive therapy includes maintaining an airway and treating seizures and dysrhythmias as they occur. b. Decontamination. Syrup of ipecac not recommended. c. Activated charcoal (repetitive doses) to enhance elimination. Whole-bowel irrigation for massive ingestions (especially with sustained-release products). Charcoal hemoperfusion is used in unstable patients who are in status epilepticus. Hemodialysis is used when hemoperfusion is unavailable. d. -adrenergic antagonists (e.g., esmolol, Brevibloc) are