Download 157 - Over-the-Counter Medications

157 Over-the-Counter
Medications
Stephen Thornton and Binh T. Ly
KEY POINTS
• Acetaminophen poisoning should be considered in
patients presenting with over-the-counter medication
misuse or overdose.
• Poisonings with antihistamine medications may
manifest with antimuscarinic toxicity and sedation, but cardiac toxicity and seizures are also possible.
• Treatment for antihistamine poisoning is supportive
care, but sodium bicarbonate and physostigmine may
be helpful adjuncts.
• Dextromethorphan poisoning manifests as sedation,
movement disturbances, and psychoactive dysphoria.
Most of these effects are mediated by N-methyl-daspartate, rather than by opioid receptor activity.
• In overdose, poisoning with oral amphetamine-like
decongestants may manifest as a sympathomimetic
toxidrome.
• Imidazoline ocular and nasal decongestants such as
oxymetazoline (Afrin) tetrahydrozoline (Visine), and
naphazoline (Naphcon) may cause significant sedation
when they are ingested orally.
• Diphenoxylate (Lomotil) can cause recurrent and
delayed respiratory depression.
• Dietary supplements are mostly safe but are
unregulated. Common conditions leading to poisoning
include mislabeling, variations in concentration,
contamination with unintended agents, and intentional
adulteration.
• Vitamin A toxicity may cause increased intracranial
pressure with associated symptoms.
• Vitamin D toxicity may cause significant hypercalcemia.
ANTIHISTAMINES
EPIDEMIOLOGY
Antihistamines are among the most frequently used medications in the United States.1 Most of these drugs are available
without a prescription. Although their efficacy is questionable, antihistamines are widely used for the symptomatic
relief of cold and allergy symptoms. They are also found in
nonprescription sleeping aids. Because of widespread access,
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these agents are commonly ingested intentionally, in suicide
attempts, and unintentionally, particularly by children.
Approximately 90,000 cases of antihistamine ingestions are
reported to poison centers in the United States every year, and
almost half of those involve children younger than 6 years.2
PATHOPHYSIOLOGY
The antihistamines function as reversible competitive inhibitors of either H1 or H2 histamine receptors. Currently available
antihistamines can be classified as first-generation, sedating
H1 receptor antagonists (e.g., diphenhydramine, hydroxyzine);
second-generation, nonsedating H1 receptor antagonists (e.g.,
loratadine, fexofenadine); or H2 receptor antagonists. Antagonism of the H1 receptors inhibits bronchoconstriction, vasoconstriction, and capillary permeability (the cause of edema
and wheal), whereas H2 receptor antagonism inhibits gastric
acid secretion. In overdose, first-generation H1 receptor antagonists may have some additional effects on other receptors
and ion channels, particularly muscarinic-type cholinergic
receptor inhibition, α-adrenergic receptor inhibition, and fast
sodium channel blockade, whereas second-generation H1
receptor blockers and H2 receptor antagonists primarily cause
sedation.
PRESENTING SIGNS AND SYMPTOMS
Patients typically present with some degree of altered mental
status or suicidality. A history of ingestion or coingestions
should be sought. Emergency medical personnel and family
members, if available, may need to be questioned. Pill bottles,
if present, may help clarify the history.
Although sedation is common with larger ingestions, signs
of antimuscarinic toxicity may also be present (Box 157.1).
In addition, patients may have mild hypotension or more worrisome wide complex dysrhythmia resulting from sodium
channel–blocking effects of some antihistamines (e.g., diphenhydramine). Cardiovascular toxicity associated with some
antihistamines is indistinguishable from that associated with
cyclic antidepressants (Fig. 157.1).
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
The differential diagnosis of antihistamine toxicity is broad
because many medications, street drugs, and disease
CHAPTER 157
processes can cause a presentation characterized by sedation
or delirium, or both (Box 157.2). The emergency physician
must consider nontoxicologic causes of altered mental status,
such as infection and traumatic brain injury, and evaluate for
these nontoxicologic conditions accordingly if the presence of
the conditions cannot be excluded by other means. Computed
tomography of the head and lumbar puncture may be warranted. In particular, patients presenting with antimuscarinic
toxicity may be delirious, hyperthermic, and tachycardic, features that mimic infectious causes.
Bedside blood glucose measurements should be performed
early in the course of management for individuals presenting
with altered sensorium. An electrocardiogram should be
obtained quickly to assess for conduction abnormalities, with
BOX 157.1 Signs of Antimuscarinic Toxicity
Delirium
Tachycardia
Anhidrosis
Mydriasis
Hyperthermia
Urinary retention
Ileus
DELIRIUM/AGITATION
• Agitation without violence
distinguishes this from
sympathomimetic toxicity
• Mumbling that almost sounds
intelligible
• Picking behavior at real objects
(buttons, your stethescope) or
imaginary ones
• MANAGEMENT: lorazepam,
physostigmine, restraints as needed;
avoid haloperidol, which can worsen
symptoms
ANHIDROSIS
• Check axilla for lack of
moisture
• Distinguishes
anticholinergic (dry) from
sympathomimetic
URINARY RETENTION
• Maintain high clinical suspicion
• Place Foley catheter if suspected
• Residual urine of more than 200-300 mL
makes the diagnosis in the patient with
altered mental status
• MANAGEMENT: Catheterization
Over-the-Counter Medications
particular attention paid to the QRS and QTc duration. Serum
electrolyte concentrations should be measured to rule out
metabolic abnormalities in patients who are confused or who
exhibit evidence of cardiotoxicity. Laboratory evaluation of
total creatinine kinase to evaluate for rhabdomyolysis may be
indicated in acutely agitated patients. Serum acetaminophen
levels should be measured in all patients with intentional
overdose, because many cough and cold preparations combine
antihistamines with antipyretics and analgesics. A urine
BOX 157.2 Drug Ingestions or Diseases That
Manifest with Sedation or Delirium
Ethanol
Benzodiazepines
Barbiturates
Opioids
Cyclic antidepressants
Antipsychotics
Anticonvulsants (carbamazepine)
Meningitis and encephalitis
Sepsis
Head injury
Metabolic derangements (hyponatremia)
MYDRIASIS
• Shared feature with
sympathomimetic poisoning
• Pupils > 5 mm in normal ED
lighting
TACHYCARDIA/CONDUCTION
DELAYS
• May be absent even in the
presence of central toxicity
(delirium)
• MANAGEMENT: no treatment
if normotensive; IV fluids and
norepinephrine if hypotension is
intractable; sodium
bicarbonate for conduction delays
HYPERTHERMIA
• Caused by anhidrosis and
impaired evaporative cooling
• Can be subtle or extreme
• Always check rectal
temperatures
• MANAGEMENT: Active
cooling with misting and
fanning, IV fluids
Fig. 157.1 Recognizing the anticholinergic toxidrome. ED, Emergency department; IV, intravenous.
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TOXICOLOGIC EMERGENCIES
immunoassay (standard urine drugs of abuse screen) may be
considered to screen for recent exposure to opioids, benzodiazepines, or other drugs, although the clinical utility of this
test is limited by frequent false-positive results. The emergency physician should recognize that a positive screening test
result indicates only exposure to and not active toxicity of a
compound. Qualitative testing for antihistamines is not useful
and generally not readily available. Diphenhydramine may
trigger a false-positive immunoassay result for tricyclic antidepressants or phencyclidine (PCP) on some urine drug
immunoassays typically used in many hospitals.
TREATMENT
Prehospital treatment of the acutely poisoned patient should
be based on providing supportive care and preventing
complications such as injury from agitation or aspiration from
decreased mental status.
Hospital treatment should also be focused on supportive
care with assessment of airway, breathing, and circulation.
Particular attention should be paid to controlling agitation
and hydration (Table 157.1). Agitation should be treated with
benzodiazepines in doses titrated to desired effect (e.g., lorazepam, 1 to 2 mg by intravenous [IV] push to effect). In addition to chemical restraint, physical restraint for patient and
staff safety may be needed. Hydration should be addressed
with 1- to 2-L boluses of 0.9% saline solution to ensure
adequate urine output.
In patients who present within 1 hour of drug ingestion
and who are alert and cooperative, activated charcoal (50 g or
1g/kg up to 50 g in children) should be considered. Data in
humans are insufficient to support the use of activated charcoal beyond 1 hour.3
Table 157.1 Toxicities of Over-the-Counter Medications
MEDICATION
TOXICITY
TREATMENT
DISPOSITION
First-generation H1 antagonists
• Diphenhydramine
• Doxylamine
Sedation
Antimuscarinic toxidrome
• Tachycardia
• Delirium
• Anhidrosis
• Mydriasis
• Hyperthermia
Rhabdomyolysis
Hypotension
Dysrhythmia
Supportive care
Benzodiazepines
Physostigmine (for
antimuscarinic delirium)
Observation
Admission for persistent
symptoms
Second-generation H1 antagonists
• Cetirizine
• Fexofenadine
• Loratadine
Sedation
Supportive care
Observation
Admission for persistent
symptoms
Sedation
Agitation
Movement disorders
Serotonin syndrome
Supportive care
Benzodiazepines for agitation
Observation
Admission for persistent
symptoms
Amphetamine-like
• Ephedrine
• Pseudoephedrine
• Phenylephrine
Sympathomimetic toxidrome
• Tachycardia
• Agitated delirium
• Hypertension
• Mydriasis
Rhabdomyolysis
Supportive care
Benzodiazepines for agitation
Vasodilators for severe
hypertension
Observation
Admission for persistent
or severe symptoms
Imidazoline
• Tetrahydrozoline
• Oxymetazoline
• Naphazoline
Sedation
Hypotension or hypertension
Bradycardia
Supportive care
Observation
Admission for persistent
or severe symptoms
Opioid toxicity
• CNS depression
• Miosis
• Respiratory depression
Supportive care
Naloxone
Admission
Awareness of recurrent
or delayed symptoms
Antihistamines
Antitussives
Dextromethorphan
Decongestants
Antidiarrheals
Diphenoxylate
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CHAPTER 157
Hyperthermia should be managed with sedation and active,
evaporative cooling (misting with water and applying direct
fanning). Rarely, endotracheal intubation with neuromuscular
paralysis may be necessary if hyperthermia or agitation fails
to improve with less aggressive measures.
Physostigmine is a reversible acetylcholinesterase inhibitor
that crosses the blood-brain barrier; it increases synaptic acetylcholine and may temporarily reverse antimuscarinic delirium. Peripheral signs may also be reversed. It may also be
used therapeutically to control agitation.4 Physostigmine may
have more value as a diagnostic tool by precluding the need
for invasive tests (e.g., lumbar puncture) if complete reversal
of delirium is achieved following administration.5 Beyond
diagnostic use, the role of physostigmine in the treatment of
most antimuscarinic poisonings with minor symptoms is
debatable, and caution should be used if a possibility of tricyclic antidepressant ingestion exists.
Severe cardiac conduction abnormalities as evidenced by
QRS prolongation should be treated with sodium bicarbonate
(1 to 2 mEq/kg IV push) to overcome impaired sodium conduction. Hypotension is usually mild and should be treated
with IV fluids. Refractory hypotension may also be treated
with sodium bicarbonate and direct-acting alpha-agonists
(norepinephrine, 2 to 12 mcg/min IV infusion).
As with all ingestions with significant toxicity, consultation
with a medical toxicologist or a poison center should be
considered.
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Patients with evidence of ongoing cardiovascular or neurologic toxicity should be admitted. Completely asymptomatic
patients who have been observed for 6 hours after drug ingestion may be medically cleared for psychiatric evaluation or
discharged, whichever is most appropriate.
ANTITUSSIVES: DEXTROMETHORPHAN
EPIDEMIOLOGY
Dextromethorphan was approved by the U.S. Food and
Drug Administration (FDA) as an over-the-counter
antitussive in 1958. It is a common component of cold
preparations, and its nonmedical use (abuse) appears to
be increasing, especially among adolescents.6 Abuse of
Coricidin (known on the streets as “Skittles”) and Robitussin
(known as “DXM” and “robo”) has highlighted dextrome­
thorphan’s abusive potential.
PATHOPHYSIOLOGY
Dextromethorphan is the structural analogue of the opioid
analgesic levorphanol that is devoid of analgesic properties
but has antitussive properties resulting from agonism of
σ-opioid receptors. In addition, dextromethorphan inhibits
N-methyl-d-aspartate (NMDA)–glutamate receptors and
alters dopaminergic and serotonergic neurotransmission.
Over-the-Counter Medications
Associated psychoactive effects are attributed to the active
metabolite dextrorphan. At very high doses, typical opioid
toxicity may be seen.
PRESENTING SIGNS AND SYMPTOMS
Some degree of altered mental status (sedation or agitation)
is the most common presenting manifestation. This feature
may impair the ability to obtain a reliable history from the
patient, and emergency medical personnel or family may need
to be questioned.
Along with altered mental status, dextromethorphan may
cause gait disturbances known as “robo-walking.”7 Serotonin
syndrome, which consists of a triad of central nervous system
(CNS) dysfunction, neuromuscular dysfunction (clonus,
hyperreflexia), and autonomic instability (tachycardia, mild
hyperthermia), may also be noted in patients with toxicity.8
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
The initial approach to patients with altered mental status
includes ruling out potential emergency conditions such as
trauma, CNS infection, and metabolic derangements. Other
common CNS depressants, such as benzodiazepines, opioids,
and ethanol, may also cause sedation. Recreational drugs of
abuse with similar actions at the NMDA receptor, such as PCP
and ketamine, may also cause dysphoria and psychoactive
features. Antimuscarinic poisoning does not result from
dextromethorphan poisoning but can occur from coingested
antihistamines such as chlorpheniramine (as found in
Coricidin).
Although structurally considered an opioid, dextromethorphan does not trigger the opiate screen on a standard urine
immunoassay, but it may result in a false-positive result for
PCP. Dextromethorphan is often formulated as a hydrobromide salt; ingestions of such a formulation may cause false
elevations of chloride on an autoanalyzer test, although true
toxicity from bromide is rare.
Emergency physicians should be mindful of potential
coingestants because many cough and cold preparations frequently contain aspirin, acetaminophen, decongestants, and
antihistamines. Acetaminophen levels should be routinely
checked in poisoned patients.
TREATMENT
Prehospital treatment of the acutely poisoned patient should
be based on providing supportive care and preventing complications such as injury from agitation or aspiration from
decreased mental status.
Hospital treatment should be focused on supportive care
with assessment of airway, breathing, and circulation. Attention should be paid to controlling agitation and hydration.
Agitation should be treated with benzodiazepines in doses
titrated to effect (IV lorazepam, 1 to 2 mg titrated to effect)
(see Table 157.1). Reducing environmental stimuli may also
be helpful. In addition to chemical restraint, physical restraint
for patient and staff safety may be needed. Hydration should
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TOXICOLOGIC EMERGENCIES
be addressed with 1- to 2-L boluses of 0.9% saline solution
to ensure adequate urine output. Decontamination with activated charcoal may be considered in an alert, cooperative
patient who presents within an hour of a possible ingestion.
Supportive care is the treatment of choice. IV naloxone (1 to
2 mg) may be given for significant sedation, although reversal
may not occur.9
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Patients with evidence of ongoing neurologic toxicity should
be admitted. Completely asymptomatic patients who have
been observed for 6 hours after drug ingestion should be
evaluated by a psychiatrist to determine whether admission is
indicated.
DECONGESTANTS:
PSEUDOEPHEDRINE, EPHEDRINE,
PHENYLEPHRINE, OXYMETAZOLINE,
AND TETRAHYDROZOLINE
EPIDEMIOLOGY
Over-the-counter decongestants rank among the top five
most commonly used medications.1 They are frequently
present in multiple ingredient cough and cold products. Some
are abused for their stimulatory effects or diverted for
the production of methamphetamines. As with other overthe-counter medications, children are frequent victims of
unintentional poisonings or dosing errors, and decongestant
exposure in this population has been linked to adverse
outcomes.2
PATHOPHYSIOLOGY
Over-the-counter decongestants have their therapeutic effects
primarily by stimulating α1-adrenergic receptors and
causing vasoconstriction and reducing edema in mucous
membranes. They fall into two main classes. This first
class is amphetamine-like substances (e.g., pseudoephedrine,
ephedrine, phenylephrine), which cause release of catecho­
lamines, and block their reuptake and breakdown and are
taken orally. The other class is imidazoline decongestants
(e.g., oxymetazoline, tetrahydrozoline, naphazoline), which
directly stimulate α-adrenergic receptors on blood vessels
and are applied topically.
PRESENTING SIGNS AND SYMPTOMS
The presenting signs and symptoms from the ingestion of
over-the-counter decongestants will vary depending on the
class ingested (see Table 157.1). Ingestion of an amphetaminelike decongestant typically presents signs and symptoms of
sympathomimetic toxicity due to the increased stimulation of
both α- and β-adrenergic receptors. This is typified by
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agitation, delirium, tachycardia, hypertension, hyperthermia,
and mydriasis. Ingestion of imidazolines, which are meant for
topical use, usually presents with sedation, bradycardia and
hypertension early with subsequent hypotension. Respiratory
depression, sedation, and miosis, mimicking opioid toxicity,
have been described.10
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
If the history of ingestion is not clear then the differential
diagnosis for decongestant ingestions can be broad, especially
considering the disparate presentations of the amphetaminelike and the imidazoline classes (see Table 157.1). Coingestions and nontoxicologic processes must be considered.
Rhabdomyolysis and cardiac ischemia should be evaluated for
in patients with significant toxicity.
TREATMENT
Standard prehospital care should be sufficient for
decongestant-toxic patients, with particular attention paid to
controlling agitation. Decontamination with activated charcoal is suitable for the alert patient with exposure in the previous hour. Agitation, tachycardia, and hypertension should be
aggressively treated with benzodiazepines (IV lorazepam, 1
to 2 mg, or IV diazepam, 5 to 10 mg, titrated to effect).
The physician must aggressively hydrate these patients
to treat rhabdomyolysis. For refractory hypertension, an
α-adrenergic antagonist (IV phentolamine, 5 mg) or a venous
and arteriolar vasodilator (IV nitroprusside, 0.3 to 10 mcg/kg/
min) should be given. In severe cases of CNS depression
after imidazoline-type decongestant overdose, IV naloxone
may be given (2 to 4 mg) but its effects are inconsistent,
and endotracheal intubation may rarely be needed to support
ventilation.11
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Symptoms of decongestant exposure, whether amphetaminelike or imidazoline, usually resolve within 8 hours or so.
However, admission of symptomatic patients may be warranted. Depending on intent, psychiatry evaluation may be
needed.
ANTIDIARRHEALS: LOPERAMIDE AND DIPHENOXYLATE
EPIDEMIOLOGY
Diarrhea remains an important and frequent health problem.
Over-the-counter remedies are often sought by diarrhea sufferers, and many different over-the-counter agents are reported
to be antidiarrheal. Loperamide (Imodium) is probably the
best known of these agents. Diphenoxylate with atropine
CHAPTER 157
(Lomotil) is a prescription medication and frequently used
interchangeably with loperamide.
PATHOPHYSIOLOGY
Loperamide and diphenoxylate are synthetic analogues of
meperidine used to treat diarrhea. Loperamide’s systemic
absorption is restricted by its insolubility, and therapeutically
only local µ-type opioid receptors in the gastrointestinal tract
are affected, resulting in decreased intestinal motility.
Diphenoxylate is combined with a small dose of atropine both
to increase its antimotility effect and to discourage its abuse
as an opioid (this combination is marketed as Lomotil).
Diphenoxylate has a significantly worse adverse effect profile
because it metabolizes to difenoxin, a compound with higher
potency and a longer serum half-life.
PRESENTING SIGNS AND SYMPTOMS
Loperamide is generally well tolerated even in large ingestions, and drowsiness is the most common effect.12 Diphenoxylate is significantly more toxic, and overdoses commonly
manifest with some degree of opioid toxicity (e.g., CNS
depression, respiratory depression, miosis, decreased bowel
motility), with or without the antimuscarinic effects of the
atropine (see Table 157.1).
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
The differential diagnosis includes conditions that cause
altered mental status and respiratory depression. No specific
tests are available to order in evaluating these patients.
Common urine drug screens do not detect either drug. Any
diagnostic tests ordered should be geared toward the standard
evaluation of the poisoned or altered patient and not these
agents in particular.
TREATMENT AND DISPOSITION
Prehospital treatment should be oriented toward providing
supportive care and preventing complications such as aspiration from decreased mental status. Prehospital administration
of naloxone may be considered.
In general, loperamide has a high safety profile and has
been associated with very few adverse events, even in overdose. However, diphenoxylate overdoses can cause significant
symptoms, usually related to respiratory depression (see Table
157.1). Respiratory depression by can be recurrent or delayed,
sometimes up to 24 hours after the ingestion, and children are
particularly at risk.13 Decontamination with activated charcoal
in the cooperative patient may be useful even beyond the 1
hour, given the impairment of gastrointestinal motility with
these agents. IV naloxone (0.4 to 2.0 mg) is effective in
reversing the respiratory depression and other signs of opioid
toxicity, but CNS and respiratory depression may recur, and
an IV naloxone infusion may be needed.13
Over-the-Counter Medications
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Patients with loperamide ingestions can typically be observed
for 6 hours and medically cleared for psychiatric evaluation
if the ingestion was intentional or discharged if unintentional.
Strong consideration should be given to admitting pediatric
patients and patients with intentional and significant Lomotil
ingestions because of the possibility of severe delayed or
recurrent symptoms (e.g., respiratory depression).
DIETARY SUPPLEMENTS
EPIDEMIOLOGY
Any ingredient taken for the purpose of promoting health is
considered a dietary supplement. Innumerable examples of
dietary supplements exist, and a national surveyed showed
that more than 15% of the U.S. population had used one or
more in the previous week.14 Ginkgo, St. John’s wort, ginseng,
echinacea, and synephrine are among the more commonly
used dietary supplements (Table 157.2). Unlike with prescription drugs, proof of safety and proof of efficacy are not
required for dietary supplements as long as the maker does
not claim that the agent is a treatment for a particular disease.
To be removed from the market, a dietary supplement must
be proven unsafe. This situation occurred in 2006, when the
FDA banned of ephedra over cardiovascular concerns.15
PATHOPHYSIOLOGY
The exact mechanism of action of many of the dietary supplements is poorly understood. Severe toxicity from most supplements remains uncommon because of the low concentrations
of specific agents in marketed products. Toxicity may arise
not only from the product itself but also from unlisted active
ingredients and from contaminants such as heavy metals.
Supplements may also have interactions with certain drugs
that affect metabolism and efficacy.
PRESENTING SIGNS AND SYMPTOMS
Depending on the specific dietary supplement, presenting
signs and symptoms vary. Table 157-2 lists some of the possible toxic manifestations of the more common dietary
supplements.
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
The differential diagnosis is driven by the particular supplement ingested. For example, ingestion of an ephedra-like
supplement (bitter orange) suggests other causes of sympathomimetic toxicity such as cocaine and amphetamines. No
diagnostic testing is specific to dietary supplements, and drug
levels are of no value.
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SECTION XV
TOXICOLOGIC EMERGENCIES
Table 157.2 Toxicities of Dietary Supplements
DIETARY SUPPLEMENT
SIGNS AND SYMPTOMS OF TOXICITY
Synephrine (bitter orange)
Sympathomimetic toxidrome
Myocardial infarction
Stroke
Ephedra (Ma-Huang)
Sympathomimetic toxidrome
Myocardial infarction
Stroke
Ginkgo (Ginkgo biloba)
GI distress, headache, allergic reaction, bleeding, seizures
St. John’s wort (Hypericum perforatum)
Photosensitization
Induction of CYP 3A4 that leads to decreased levels of certain drugs
Serotonin toxicity from weak MOAI properties
Ginseng (Panax ginseng)
Ginseng abuse syndrome (hypertension, sleepiness, nervousness, morning
diarrhea)
Echinacea (Echinacea purpurea)
Normally none
Rarely hepatitis, asthma, anaphylaxis
Kava kava (Piper methysticum)
Mild euphoria, sedation, muscle weakness
Rarely hepatotoxicity
Nutmeg (Myristica fragrans)
GI upset, hallucinations
Hydroxycut (Garcinia cambogia extract,
chromium polynicotinate, Gymnema sylvestris
extract, and Camellia sinensis)
Hepatotoxicity, seizures
GI, Gastrointestinal; MAOI, monoamine oxidase inhibitor.
TREATMENT
Dietary supplement exposures pose unique challenges
because of the lack of information on the toxicologic profiles,
pharmacokinetics, and concentrations of their active ingredients. Most cases of toxicity stemming from therapeutic use
can be managed with supportive care and symptom-based
therapy.
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Symptomatic patients should be admitted for observation and
symptomatic therapy. A psychiatric consultation should be
obtained when warranted. Patients who are asymptomatic 4
to 6 hours after an acute accidental overdose of a known agent
with known safety profiles can be discharged with appropriate
follow-up.
VITAMINS
EPIDEMIOLOGY
Vitamins are frequently taken in supratherapeutic amounts.
This is done typically under the premise of “more is better”
or purportedly to treat or prevent conditions ranging from
viral upper respiratory tract infections to Alzheimer dementia.
1340
Parents’ concern about their children’s eating patterns may
result in vitamin oversupplementation.16 All these factors,
added to the ready availability of vitamins, make vitamins
prime targets for potential toxic exposures.17
PATHOPHYSIOLOGY
Vitamins can be grouped into two main categories: water
soluble and fat soluble. Toxicity may be caused by either
group, though in general toxicity from water-soluble vitamins
are rarer and less severe as they do not accumulate as fatsoluble vitamins do. Vitamin A and D, which are both fat
soluble, have well described toxicity. Table 157.3 describes
the normal function of the most common vitamins and their
toxic effects.
PRESENTING SIGNS AND SYMPTOMS
The presenting signs and symptoms of hypervitaminosis
depend on the offending vitamin.16-19 Table 157.3 lists the
toxic effects of the most clinically relevant vitamins.
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
Because of the relative infrequency of severe toxicity from
hypervitaminosis, the more common causes of such conditions as sensory neuropathies, increased intracranial pressure,
CHAPTER 157
Over-the-Counter Medications
Table 157.3 Functions and Toxicities of Vitamins
VITAMIN
NORMAL FUNCTION(S)
TOXIC EFFECTS
TREATMENT
Vitamin A
Vision
Gene transcription
Skin health
Increased intracranial pressure
Headaches
Vomiting
Lethargy
Hepatotoxicity
Alopecia
Cessation of exposure
Supportive care
Rarely: mannitol, steroids,
hyperventilation for
increased intracranial
pressure
Vitamin D
Calcium homeostasis
Hypercalcemia
GI upset
Lethargy
Weakness
Hypertension
Renal injury
Cessation of exposure
Intravenous hydration
Loop diuretics
Glucocorticoids
Calcitonin
Vitamin E
Cell membrane antioxidation
Coagulopathy
Cessation of exposure
Rarely: FFP and platelet
transfusion
Vitamin K
Coagulation
Rarely reported
Hepatotoxicity?
Cessation of exposure
Vitamin C
(ascorbic acid)
Collagen synthesis
Carnitine synthesis
Neurotransmitter synthesis
Antioxidation
GI upset
Hematuria
Nephrolithiasis
Anemia
Cessation of exposure
Supportive care
Vitamin B6
(pyridoxine)
Neurotransmitter metabolism
Neuropathy
Paresthesias
Weakness
Hyporeflexia
Cessation of exposure
Vitamin B3 (niacin)
NAD+/NADP+ precursor
status
Histamine release
Flushing (acute)
Hepatotoxicity
Gout
Cessation of exposure
Antihistamines
Aspirin
Fat Soluble
Water Soluble
FFP, Fresh frozen plasma; GI, gastrointestinal; NAD+/NADP+, oxidized nicotinamide adenine dinucleotide/oxidized nicotinamide adenine dinucleotide
phosphate.
and hypercalcemia must be explored first. The diagnosis of a
vitamin overdose is most often made from a history of ingestion. In patients with vitamin A toxicity, elevations of aminotransferase, alkaline phosphatase, and bilirubin concentrations,
as well as prothrombin time, are indicators of hepatic toxicity.
Computed tomography of the head or lumbar puncture with
measurement of the opening pressure should be performed to
confirm increased intracranial pressure. Vitamin D toxicity
can be demonstrated with elevated calcium and vitamin D
levels. Because many vitamin preparations contain iron or
fluoride, these agents must be considered and evaluated as
possible coingestants.
TREATMENT
Typically, supportive care and cessation of the offending
vitamin are sufficient to treat most vitamin toxicities. In the
case of vitamin A toxicity, measures to reduce intracranial
pressure may be warranted, and in the case of vitamin D
TIPS AND TRICKS
• Many vitamin preparations contain iron or fluoride, so it
is imperative that these agents be considered and evaluated as possible coingestants.
• In patients with mixed ingestion, older patients, or very
young patients, physical findings may be variable and the
clinical picture unclear.
• Peripheral findings do not always accompany central
findings in antihistamine overdose; therefore, a confused
patient may not always have tachycardia or anhidrosis.
• In all cases of potential poisoning, nontoxicologic causes
of altered mental status should also be considered.
• With dextromethorphan ingestions, genetic differences in
speed of metabolism of the drug to dextrorphan can
result in either predominance of sedation or dysphoria.
1341
SECTION XV
TOXICOLOGIC EMERGENCIES
toxicity, standard treatment for hypercalcemia (IV hydration
and loop diuretics) should be employed (see Table 157.3).
FOLLOW-UP, NEXT STEPS IN CARE, AND PATIENT EDUCATION
Patients who are toxic from fat-soluble vitamin overdoses
typically need admission because the effects of these agents
may be prolonged. All patients should be educated on the risk
of hypervitaminosis.
SUGGESTED READINGS
Chyka PA, Erdman AR, Manoguerra AS, et al. Dextromethorphan poisoning: an
evidence-based consensus guideline for out-of-hospital management. American
Association of Poison Control Centers. Clin Toxicol (Phila) 2007;45:662-77.
1342
Daggy A, Kaplan R, Roberge R, Akhtar J. Pediatric Visine (tetrahydrozoline)
ingestion: case report and review of imidazoline toxicity. Vet Hum Toxicol
2003;45:210-12.
Haller C, Benowitz NL. Adverse cardiovascular and central nervous system events
associated with dietary supplements containing ephedra alkaloids. N Engl J Med
2000;343:1833-8.
Tovar RT, Petzel RM. Herbal toxicity. Dis Mon 2009;55:592-641.
REFERENCES
References can be found
www.expertconsult.com.
on
Expert
Consult
@
CHAPTER 157
REFERENCES
1. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent patterns of medication use in
the ambulatory adult population of the United States: the Slone survey. JAMA
2002;287:337-44.
2. Bronstein AC, Spyker DA, Cantilena Jr LR, et al. 2009 annual report of the
American Association of Poison Control Centers’ National Poison Data System
(NPDS): 27th annual report. Clin Toxicol (Phila) 2010;48:979-1178.
3. Chyka PA, Seger D, Krenzelok EP, Vale JA. American Academy of Clinical
Toxicology; European Association of Poisons Centres and Clinical Toxicologists:
position paper. Single-dose activated charcoal. Clin Toxicol (Phila)
2005;43:61-87.
4. Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and
benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med
2000;35:374-81.
5. Schneir AB, Offerman SR, Ly BT, et al. Complications of diagnostic
physostigmine administration to emergency department patients. Ann Emerg Med
2003;42:14-19.
6. Bryner JK, Wang UK, Hui JW, et al. Dextromethorphan abuse in adolescence:
an increasing trend: 1999-2004. Arch Pediatr Adolesc Med 2006;160:1217-22.
7. Warden CR, Diekema DS, Robertson WO. Dystonic reaction associated with
dextromethorphan ingestion in a toddler. Pediatr Emerg Care 1997;13:214-15.
8. Schwartz AR, Pizon AF, Brooks DE. Dextromethorphan-induced serotonin
syndrome. Clin Toxicol (Phila) 2008;46:771-3.
Over-the-Counter Medications
9. Chyka PA, Erdman AR, Manoguerra AS, et al. Dextromethorphan poisoning: an
evidence-based consensus guideline for out-of-hospital management. American
Association of Poison Control Centers. Clin Toxicol (Phila) 2007;45:662-77.
10. Daggy A, Kaplan R, Roberge R, Akhtar J. Pediatric Visine (tetrahydrozoline)
ingestion: case report and review of imidazoline toxicity. Vet Hum Toxicol
2003;45:210-12.
11. Wiley 2nd JF, Wiley CC, Torrey SB, Henretig FM. Clonidine poisoning in young
children. J Pediatr 1990;116:654-8.
12. Litovitz T, Clancy C, Korberly B, et al. Surveillance of loperamide ingestions:
an analysis of 216 poison center reports. J Toxicol Clin Toxicol 1997;35:11-19.
13. McCarron MM, Challoner KR, Thompson GA. Diphenoxylate-atropine (Lomotil)
overdose in children: an update (report of eight cases and review of the
literature). Pediatrics 1991;87:694-700.
14. Kelly JP, Kaufman DW, Kelley K, et al. Recent trends in use of herbal and other
natural products. Arch Intern Med 2005;165:281-6.
15. Haller C, Benowitz NL. Adverse cardiovascular and central nervous system
events associated with dietary supplements containing ephedra alkaloids. N Engl
J Med 2000;343:1833-8.
16. Herbert V. The vitamin craze. Arch Intern Med 1980;140:173-6.
17. Bendich A. Safety issues regarding the use of vitamin supplements. Ann N Y
Acad Sci 1992;669:300-10; discussion 311-12.
18. Omaye ST. Safety of megavitamin therapy. Adv Exp Med Biol 1984;177:169-203.
19. Alhadeff L, Gualtieri CT, Lipton M. On the toxicity of water-soluble vitamins.
Nutr Rev 1984;42:265-7.
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