Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants.

1. Clinical toxicology
TAYYABA MUMTAZ

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

3. Information resources
 1. Computerized databases a. POISINDEX is a database that is
updated quarterly and is a primary resource for poison control centers.
 2. Printed publications. Textbooks and manuals provide useful
information regarding the assessment and treatment of patients exposed to
various substances, although their usefulness is limited by the lag time of
information published in the primary literature reaching updated editions.

4.  Internet
 a. Centers for Disease Control and Prevention (CDC) at http://www.cdc.gov
 b. U.S. Food and Drug Administration (FDA) at http://www.fda.gov
 c. National Library of Medicine at http://www.nlm.nih.gov
 d. National Institute for Occupational Safety and Health (NIOSH) at
http://www.cdc.gov/niosh
 e. American Society of Health–System Pharmacists at http://www.ashp.org
 f. Material Safety Data Sheets at http://www.msdssearch.com g. U.S. Environmental
Protection Agency (EPA) at http://www.epa.gov
 4. Poison control centers accredited by the American Association of Poison
Control Centers (AAPCC) provide information to the general public and health care
providers.

5. 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.

6. 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 pre hospital 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 burning or irritation of the upper airway.
 4. Gastrointestinal (GI) examination evaluates any abdominal pain, nausea,
vomiting, diarrhea, or difficulty in swallowing.

7.  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 neglect
 j. Last normal menstrual period or pregnancy

8.  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

9. Toxicology laboratory tests
 1. Advantages
 a. Confirm or determine the presence of a particular agent
 b. Predict the anticipated toxic effects or severity of exposure to some poisons
 c. Confirm or distinguish differential or contributing diagnosis
 d. Occasionally help guide therapy
 2. Disadvantages
 a. These tests cannot provide a specific 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.

10.  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.
 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.

11.  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

12.  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.
 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.

13.  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 children 1 to 12 years of age is 25 to 50 g; the dose in
children up to 1 year of age is 1 g/kg. 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 embalances and/or dehydration.
 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.

14.  Forced diuresis and urinary pH manipulation may be used to enhance the
elimination of substances
 Alkaline diuresis
 Dialysis
 Hemoperfusion is a technique in which anticoagulated blood is passed through
(perfused) a column containing activated charcoal or resin particles.

16. MANAGEMENT OF SPECIFIC
INGESTIONS
 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.

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

18.  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).
 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

19.  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%
contains 200 mg/mL. 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.

20.  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.

21. Alcohols
 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.

23. 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, costovertebral angle tenderness, oliguric renal failure

24.  d. Laboratory data may reveal severe metabolic acidosis,
hypocalcemia, and calcium oxalate crystals in the urinalysis.

25. 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 of 1.4 mL/kg/hr.
(iii) Infusion rates may need to be increased in patients receiving hemodialysis.

26.  (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% s
odium 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.

27.  (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.

28. 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.
 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 respiratory depression, seizures, and death.

29.  Laboratory data include severe metabolic acidosis, hyperglycemia, and
hyperamylasemia.
 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

30.  .(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.

31. Anticoagulants. 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.

32.  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.

33.  (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.
 (d) These overdoses should be referred to a hematologist and/or the poison
control center.

34. 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.

35. 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 hemorrhage, the
ACCP recommends the use of prothrombin complex concentrates or recombinant
factor VIIa to immediately reverse the INR.

36. Pradaxa (dabigatran)
 a. Available dosage forms include oral capsules.
 b. Toxicokinetics. Dabigatran is poorly absorbed following oral administration,
but it has a halflife 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.

37. 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 first FDA-approved oral direct-acting thrombin inhibitor.

38. 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.

39.  Clinical Presentation. Anticholinergic effects 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.
 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.

40.  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 a
systole, the use of this antidote for TCA overdoses is declining.

41. Selective serotonin reuptake inhibitors (SSRIs)
 Available forms (nontricyclic agents) include fluoxetine (Prozac), sertraline (Zoloft ),
and paroxetine (Paxil).
 Toxicokinetics. SSRIs are well absorbed after oral administration. Peak levels
occur within 2 to 6 hrs. SSRIs are hepatically metabolized with a half-life between 8
and 30 hrs.
 Clinical presentation includes mild symptomatology. Patients may become
agitated, drowsy, or confused. Seizures and cardiovascular toxicity are rare.
 Laboratory data. ECG monitoring is recommended. Blood level monitoring is not
recommended.
 Treatment includes gastric lavage and supportive treatment. Some toxicologists may
recommend the use of cyproheptadine (Periactin) to manage the serotonin
syndrome, which may manifest as a result of these ingestions.

42. Benzodiazepines
 1. Available forms include chlordiazepoxide (Librium), diazepam
(Valium), flurazepam (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.

43.  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.

44. Beta-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 glucose (patients
may become hypoglycemic).

45. 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 beta -blocker overdoses.
 d. Calcium salts
 e. High-dose insulin dextrose

46. 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 reported.
4. Laboratory data include ECG and serum electrolytes.

47. 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 B-blocker overdose.
 d. Combined insulin and dextrose administration has been used in selected
cases.
 e. Phosphodiesterase inhibitors. Inamrinone or milrinone.

48. Cocaine
 1. Available forms include alkaloid obtained from Erythroxylon coca.
 2. Toxicokinetics. Cocaine is well absorbed aftr 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.
 5. Treatment is supportive: benzodiazepines for sedation seizure treatment,
labetalol (Normodyne) for hypertension.

49. Corrosives
 1. Available forms include strong acids or alkalis.
 2. Toxicokinetics. Corrosives are well absorbed after 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 further tissue damage.

50. Cyanide
 1. Available forms include industrial chemicals and some nail polish
removers.
 2. Toxicokinetics. The drug is rapidly absorbed after 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.

51. 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 are available for pediatric dosing.

52. 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.

53. Treatment
 a. Decontamination with activated charcoal is recommended.
 b. Supportive therapy includes managing hyperkalemia or hypokalemia and
inotropic support as needed.
 c. Digoxin-specific Fab antibodies (Digibind).

54. 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 reflexes may be depressed; lethargy and weakness
 (2) Severe. Respiratory paralysis and heart block
 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.

55. Potassium
 a. Available dosage forms are oral and parenteral.
 b. Toxicokinetics. Potassium is primarily an intracellular cation. Changes in
acid–base balance produce shifts 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.
d. Laboratory data. ECG

56.  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 fluid into the
cells.
 (4) Cation exchange resins bind potassium in exchange for another cation
(sodium).


57. 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
 c. Phase III. Metabolic acidosis, renal and hepatic failure, sepsis, pulmonary edema,
and death
 4. Laboratory data include serum Fe levels, total iron-binding capacity, ABGs, liver
function tests (LFTs), hemoglobin, and hematocrit.

58.  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 6 to 8 g/day. Continue until patient is clinically
stable.

59. 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.

60.  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 Daxtrose and infused at 0.5 g/min until seizures stop, (maximum adult
dose: 5 g).
 c. Sodium bicarbonate corrects the acidosis.

61. 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 blood-lead level. 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 is given 4 mg/kg IM every 4 hrs for 3 to 5 days.
 Dimercaprol therapy is administered first. 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.

62. Lithium
 1. Available dosage forms include liquid, capsules, and tablets (immediate and
sustained release).
 2. Toxicokinetics. Lithium is well absorbed after 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
 b. Severe. Delirium, coma, seizures, and hyperthermia
 4. Laboratory data
 a. Therapeutic range: 0.6 to 1.2 mEq/L b. Mild toxicity: 1.5 to 2.5 mEq/L c. Moderate
toxicity: 2.5 to 3.0 mEq/L d. Severe toxicity: 3.0 mEq/L

63. Treatment
 a. Supportive care, including basic life support and fluid and electrolyte
replacement
 b. Decontamination (1) Syrup of ipecac not recommended
 (2) Activated charcoal ineffective
 (3) Sodium polystyrene sulfonate has been effective 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 after dialysis
owing to a rebound eff ect.

64. 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.
 4. Laboratory data include baseline ABGs and toxicology screens.
 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.

65. 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 peripheral muscarinic effects.
c. Pralidoxime is given 1 g IV over 2 mins and repeated in 20 mins as needed.

66. Salicylates
 1. Available dosage forms include several OTC products: oral, rectal, and
topical.
 2. Toxicokinetics. Salicylates are well absorbed after 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, and malaise (mild
toxicity). Lethargy, convulsions, coma, and metabolic acidosis appear in more
severe overdoses. Potential complications from therapeutic and toxic doses
include GI bleeding, increased PT, hepatic toxicity, pancreatitis, and proteinuria.

67.  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.

68.  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.
 d. Fluid and electrolyte replacement is administered as needed.
 e. Vitamin k and fresh frozen plasma are used to correct any coagulopathy.

69. 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 definitive identification.
 2. Toxicokinetics. Onset of symptomatology depends on the species of snake and
the patient’s underlying medical condition.
 3. Clinical presentation includes nausea; vomiting; diarrhea; syncope; tachycardia;
and cold, clammy skin. Local findings include pain, edema, and erythema. More
severe envenomations can lead to severe tissue injury, compartment syndrome, and
shock.
 4. Laboratory data a. CBC and platelet count b. Coagulation profile c. Fibrin
degradation products d. Electrolytes e. BUN, SCr, and urinalysis

70. 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 or
more vials.
 (2) Crotalidae polyvalent immune Fab is a polyvalent antivenin made from sheep
sources. The initial dose is four to six vials diluted in 250 mL of 0.9% normal saline
(NS) administered over 1 hr. Additional doses may be required for severe
envenomations.

71. 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.
Theophylline 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 prognosis than acute toxicity.
 4. Laboratory data. Therapeutic theophylline levels are 5 to 20 g/mL. Hyperglycemia
and hypokalemia are seen with acute ingestions. Other useful laboratory tests include
serum electrolytes, BUN, creatinine, hepatic function, and ECG monitoring.

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