| Toxicon: Acetaminophen
(Tylenol ®
and others) |
| Source: NSAID |
| Mechanism of Action: Acetaminophen
is rapidly absorbed from the stomach and small intestine and metabolized
by conjugation in the liver to nontoxic agents, which then are eliminated
in the urine. In acute overdose or when maximum daily dose is exceeded over
a prolonged period, the normal pathways of metabolism become saturated.
Excess acetaminophen is then metabolized in the liver via the mixed function
oxidase P450 system to a toxic metabolite. Under conditions
of excessive metabolite formation or reduced glutathione stores, the reactive
metabolite is free to covalently bind to vital proteins and the lipid bilayer
of hepatocytes; this results in hepatocellular death and subsequent centrilobular
liver necrosis. |
| Symptoms: 0-24 hr: asymptomatic,
pallor, anorexia, nausea & vomiting, malaise;
18-72 hr: right upper quadrant abdominal pain & rising
liver enzymes (AST & ALT), tachycardia, hypotension; after
3-4 days: hepatic dysfunction with jaundice, recurrence of nausea
& vomiting, renal failure, possible death; otherwise
after 4day - 3 week: resolution of symptoms. |
Antidote/Treatment: The antidote for
acetaminophen poisoning is N-acetylcysteine (Mucomyst ®).
It increases glutathione stores, combines directly with acetaminophen's
reactive metabolite as a glutathione substitute, and enhances sulfate conjugation.
It also functions as an anti-inflammatory and antioxidant.
Oral activated charcoal avidly adsorbs acetaminophen &
should be given within 1-2 hours after ingestion of acetaminophen, or if
the time of ingestion is unknown. Supportive therapy, including
IV fluids, oxygen, and cardiac monitor |
| Notes: Acetaminophen is the most widely
used pharmaceutical analgesic and antipyretic agent in the United States
and the world. It is contained in more than 100 products. As such, acetaminophen
is one of the most common pharmaceuticals associated with both intentional
and accidental poisoning.The toxic dose of APAP after a single acute ingestion
is 150 mg/kg or approximately 7 g in adults, although the at-risk dose may
be lower in persons with alcoholism and other susceptible individuals. When
dosing recommendations are followed, the risk of hepatotoxicity is extremely
small. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Amphetamines
|
| Source: drug of abuse |
| Mechanism of Action: CNS and peripheral
stimulant. Cause the release of catecholamines (dopamine, norepinephrine
& serotonin) from nerve terminals. The signs & symptoms of amphetamine
overdose are generally similar to those of cocaine; however, while effects
of cocaine last for 10-20 minutes, the duration of amphetamine action is
much longer, lasting as long as 10-12 hours. |
| Symptoms:agitation & hyperactivity, euphoria,
skin flushing, chest pain, palpitations, dry mouth,
hyperthermia, nausea & vomiting, mydriasis,
anorexia & weight loss, symptoms of stroke. |
| Treatment: Patients with amphetamine
intoxication manifesting no life-threatening signs or symptoms may be treated
with sedation and observation and may require no laboratory
workup. Patients suffering seizures or prolonged mental status changes require
glucose and electrolyte testing. Complications may require the physician
to perform procedures to establish airway management, fluid resuscitation,
or initiate vigorous cooling measures. Use benzodiazepine
sedation (nonspecific sympatholysis) to initially manage hypertension, if
present. Aggressively cool hyperthermic patients with evaporative
cooling and ice packs to the groin and axilla |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Anticholinergics
(antimuscarinics) |
| Source: Atropine-like
drugs, H-1blockers, plants (jimson weed, nightshade & various "non
commercial" mushrooms). |
| Mechanism of Action: block muscarinic
receptors in the CNS and peripheral nervous system. |
| Symptoms: red as a beet, dry as a
bone, blind as a bat, mad as a hatter, and hot as a hare." The mnemonic
refers to the symptoms of flushing, dry skin
and mucous membranes, mydriasis with loss of accommodation,
altered mental status, and fever, respectively.
Also: tachycardia, urinary retention, decreased bowel sounds. |
| Antidote/Treatment: The antidote for
anticholinergic toxicity is physostigmine salicylate. Physostigmine
is the only reversible acetylcholinesterase inhibitor capable of directly
antagonizing the CNS manifestations of anticholinergic toxicity; it is an
uncharged tertiary amine that efficiently crosses the blood brain barrier.
(However, physostigmine is contraindicated in patients with cardiac conduction
disturbances such as prolonged PR and QRS intervals). GI decontamination
with activated charcoal is usually necessary after anticholinergic
poisoning by ingestion. Ipecac syrup is contraindicated because of the potential
for seizures. Most anticholinergic agents have large volumes of distribution
and are highly protein-bound; therefore, hemodialysis and hemoperfusion
are ineffective treatment methods. Following GI decontamination, patients
often recover well with supportive care. Manage seizures with
benzodiazepines, preferably diazepam or lorazepam. Phenothiazines
are contraindicated because of their anticholinergic properties. Perform
bladder catheterization if signs or symptoms of urinary retention exist |
| Notes: According to the American Association
of Poison Control Centers, almost 2.2 million cases of human poison exposure
were reported to 65 US poison control centers in 1998. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Arsenic |
| Source: Arsenic poisoning occurs through
industrial exposure (e.g. metal foundaries, glass production & semiconductor
industries), rodenticide, from contaminated wine, or because of malicious
intent (remember the Borgias). |
| Mechanism of Action: Inorganic forms
of arsenic are more toxic than organic forms. Very few organ systems escape
the toxic effects of arsenic. Trivalent inorganic arsenic inhibits pyruvate
dehydrogenase (via binding to sulfhydryl groups), resulting in decreased
citric acid cycle activity, and decreased production of cellular ATP. Trivalent
arsenic inhibits numerous other cellular enzymes through sulfhydryl group
binding. Trivalent arsenic inhibits cellular glucose uptake, gluconeogenesis,
fatty acid oxidation, and further production of acetyl CoA; it also blocks
the production of glutathione, which prevents cellular oxidative damage.
|
| Symptoms: Acute
exposure: garlic smell on the breath
& tissue fluids, acute distress, dehydration (often), choleralike gastrointestinal
symptoms of vomiting and severe diarrhea (watery
& bloody) and hypovolemic shock. Chronic
exposure: whitish lines (Mees lines)
that look much like traumatic injuries are found on the fingernails, peripheral
neuorpathy & dermal hyperpigmentation/ depigmentation
(salt/pepper) of the skin, scaly palms, hepatic & renal damage,
prolongation of the QT, cardiac arrhythmias & ventricular fibrillation.
Microcytic hyprochromic anemia is also common with all heavy metal intoxications. |
| Treatment: Dimercaprol (BAL
in oil) is a first line agent in arsenic poisoning. (Some other chealators
may also be effective although they are not approved for this indication.)
Hemodynamic stabilization (crystalloid solutions - to replace what is lost
by diarrhea & vomiting). Do not delay with definitive chelation therapy
and hemodialysis. Activated charcoal does not absorb arsenic very well.
The use of GI decontamination is controversial. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Barbiturates |
| Source: sedative/hypnotic/anesthetic |
| Mechanism of Action: .Barbiturates
bind to specific sites on gamma-aminobutyric acid (GABA)-sensitive ion channels
found in the central nervous system (CNS), where they allow an influx of
chloride into cell membranes and, subsequently, hyperpolarize the postsynaptic
neuron. |
| Symptoms: Neurologic: lethargy,
coma, hypothermia, decreased pupillary
light reflex, nystagmus, impairment in thinking, respiratory depression,
tachycardia or bradycardia, hypotension |
| Treatment: ABCs. Check for hypothermia
(& if present, warm the patient to avoid preciptating a fall in blood
pressure). Perform GI decontamination once the airway is protected and hemodynamic
stabilization addressed. Activated charcoal orally or by
nasogastric tube is recommended for all patients with potential barbiturate
toxicity. (Induction of emesis with ipecac syrup is contraindicated in these
patients because the depressed neurologic response increases risk of aspiration).
Alkalinization of the urine with sodium bicarbonate
to enhance the elimination of phenobarbital and, likely, other long-acting
barbiturates by ion trapping. Urinary alkalinization is not recommended
for short-acting barbiturate toxicity. Aggressively initiate fluid
therapy if the patient is hypotensive or appears to be
in hypovolemic shock. Hemodialysis and hemoperfusion enhance
elimination of barbiturates. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Benzodiazepines |
| Source: sedative hypnotic, antiepileptic |
| Mechanism of Action: potentiates the
activity of GABA. In the CNS this results in sedation, striated muscle relaxation,
anxiolysis, and anticonvulsant effects. Stimulation of peripheral nervous
system (PNS) GABA receptors may cause decreased cardiac contractility, vasodilation,
and enhanced perfusion. |
| Symptoms: drowsiness, nystagmus,
confusion, slurred sppech, ataxia, coma, weakness,
amnesia, hypotension, respiratory depression |
| Antidote/Treatment: Flumazenil
is the DOC to reverse effects of benzodiazepines. Other treatments: ABCs.
Single-dose activated charcoal is recommended for GI decontamination
in patients who present within 4 hours of ingestion or in symptomatic patients
when the time of ingestion is unknown.Ipecac syrup is contraindicated for
prehospital or hospital use because of the risk for CNS depression and subsequent
aspiration with emesis. Respiratory depression may be treated with assisted
ventilation. |
| Notes: In 1998, a total of 40,004
benzodiazepine exposures were reported to US poison control centers. Benzodiazepines
generally are thought to be safe and death is rare. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Carbon monoxide
(CO) |
| Source: a colorless, odorless gas
produced by incomplete combustion of organic compounds. Although most fatalities
result from fires, stoves, portable heaters, and automobile exhaust cause
approximately one third of deaths. These often are associated with malfunctioning
or obstructed exhaust systems and suicide attempts. Cigarette smoke is a
significant source of CO. Natural gas contains no CO, but improperly vented
gas water heaters, kerosene space heaters, charcoal grills, hibachis, and
Sterno stoves all emit CO. |
| Mechanism of Action: CO toxicity causes
impaired oxygen delivery and utilization at the cellular level. CO affects
several different sites within the body but has its most profound impact
on the organs with the highest oxygen requirement (eg, brain, heart). Toxicity
primarily results from cellular hypoxia caused by impedance of oxygen delivery.
CO reversibly binds hemoglobin, resulting in relative anemia. Because it
binds hemoglobin 230-270 times more avidly than oxygen, even small concentrations
can result in significant levels of carboxyhemoglobin (HbCO). |
| Symptoms: Malaise, flulike
symptoms, fatigue, dyspnea on exertion, chest
pain, confusion, lethargy, dizziness,
coma, death. |
| Treatment: 100% oxygen or
hyperbaric oxygen. |
| Notes: Misdiagnosis commonly occurs
because of the vagueness and broad spectrum of complaints; symptoms often
are attributed to a viral illness. Specifically inquiring about possible
exposures when considering the diagnosis is important. Lab test: HbCO analysis
requires direct spectrophotometric measurement in specific blood gas analyzer. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Caustic agents
(acid or base) |
| Source: corrosive agent toxicity,
acidic or alkaline substance toxicity, toilet bowl cleaning product ingestion,
automotive battery liquid ingestion, rust removal product ingestion, metal
cleaning product ingestion, cement cleaning product ingestion, drain cleaning
product ingestion, etc. |
| Mechanism of Action: Alkaline ingestions
cause tissue injury by liquefactive necrosis (saponification of fats and
solubilization of proteins). The hydroxide ion of the base reacts with tissue
collagen and causes it to swell and shorten. Small vessel thrombosis and
heat production occurs. Acid ingestions cause tissue injury by coagulation
necrosis (desiccation or denaturation of superficial tissue proteins). |
| Symptoms:Oropharyngeal burns, dyspnea &
impending airway obstruction, drooling, nausea & vomiting |
| Treatment: Airway control (equipment
for endotracheal intubation should be made available); gastric lavage.
DO NOT ADMINISTER EMETICS because of risk of re-exposure
to the caustic agent. If within 30 min of ingestion, try dilution:
tap water in doses of 250 cc for adults and 5 cc/kg in
children can be given. Do not administer a weak acid in alkaline ingestions
or a weak base in acid ingestions. Excessive heat production and risk of
emesis make this a hazardous intervention. Antibiotics (ampicillin)
can be given for prophylaxis if there is evidence for perforation. H-2
receptor antagonists may reduce exposure of injured esophagus to
gastric acid. Glucocorticoids may help prevent esophageal
strictures. |
| Notes: Ingestion of caustic substances,
accidental and intentional, is an extremely common event. Approximately
80% of caustic ingestions occur in children younger than 5 years. Most intentional
ingestions occur in adults. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Cocaine |
| Source: drug of abuse |
| Mechanism of Action: CNS stimulant
(blocks the reuptake of catecholamines:5-HT, DA, NorEpi); Na and K channel
blocker; commonly coadministered with ethanol to create cocaethylene which
has a longer half-life |
| Symptoms:Chest pain, MI, arrhythmias,
cardiomyopathy, hypertension, psychatric symptoms (including
paranoia, psychosis & the sensation of something
crawling on the skin or itchy skin), seizures,
hyperthermia, hypertension, tachycardia, dilated
pupils (mydriasis). Most acute cocaine-related nontraumatic deaths
are the result of tachydysrhythmias. Other causes of sudden
death associated with cocaine use include stroke, subarachnoid hemorrhage,
hyperthermia, and the consequences of agitated delirium. MI can result from
acute vasospasm, dysrhythmias, or chronic accelerated atherogenic disease.
|
| Treatment: Establish ABC's,
provide oxygen, i.v. access, monitor vital signs & glucose levels, administer
benzodiazepines to manage seizures. Warning: cocaine toxicity
can cause patients to become aggressive, & combative. The role of lidocaine
in treating ventricular arrhythmias is unclear (there are concerns with
it's use due to the fact that it is a Na channel blocker - like cocaine,
and "may" worsen cardiac conduction disturbances or induce seizures).
Non-selective beta blockers should be avoided. Administer sodium
bicarbonate to manage acidosis. Nitroglycerin for cocaine-related
MI if present. Treat hyperthermia with convection cooling
(spray patient with tepid water in the presence of fans), ice packs or cooling
blankets. In the absence of serious toxic reactions, the (non-lethal)
acute effects of cocaine are generally short-lived due to its short
half life (~50 mins) although this may be prolonged 2-3 fold if alcohol
is coingested. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Cyanide |
| Source: fumigates & insectisides
(e.g. termites), smoke inhalation from industrial fires |
| Mechanism of toxicity: Cyanide affects
virtually all body tissues, attaching itself to ubiquitous metalloenzymes
and rendering them inactive. Its principal toxicity probably results from
inactivation of cytochrome oxidase (cytochrome aa3) and, thus, cellular
respiration, even in the presence of adequate oxygen stores. Consequently,
the tissues with the highest oxygen requirements (eg, brain, heart, liver)
are the most profoundly affected by acute cyanide poisoning. Cyanide cabinduce
fatality in seconds to minutes following inhalation or intravenous injection,
in minutes following ingestion of soluble salts, or minutes (hydrogen cyanide)
to several hours (cyanogens) after skin absorption. |
| Symptoms: bitter almond odor on breath, bitter
taste, burning throat, lock jaw, convulsions, coma, respiratory failure. |
| Antidote: ABC's including aggressive
airway management with delivery of 100% oxygen, amyl nitrite (inhaled),
sodium nitrite (i.v.) to induce the formation of methemoglobin
(F3+) from hemoglobin, which will bind cyanide to form a non-toxic complex.
Treatment must be rapid (w/in 5-10 min). Sodium thiosulfate
(Tinver ®) -- Second-line therapy because of slower mechanism of action.
Regenerates sulfur-dependent rhodanese activity. Coadminister with or after
sodium nitrite or hydroxocobalamin. Useful adjunct in prolonged (cyanogen)
poisonings. |
| Reference:http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Digoxin |
| Source: positive intropic drug |
| Mechanism of Toxicity: inhibits Na/K
ATPase; cardiac arrhythmias (delayed after-depolarizations w/ abnormal automaticity,
depolarization & conduction block, 1st - 3rd degree AV node conduction
block, enhanced vagal tone); CNS effects |
| Symptoms: GI disturbances
(abdominal pains, diarrhea), cardiac arrhythmias &
ECG changes (various arrhythmias, bigeminy, 1st-3rd AVN block;
ST depression, etc.); neurological (nausea, vomiting, fatigue,
anorexia, dizziness, dreams, psychic complaints, headache), visual
disturbances (yellow green color hues, halos, blurred vision, photophobia).
|
| Antidote/Treatment: Digoxin
Fab fragments (Digibind) are generally indicated for potentially
fatal overdose (e.g. hemodynamically unstable arrhythmias, hyperkalemia
greater than 6 mM, digoxin level greater than 10 ng/ml in adults or ingestion
of greater than 10 mg = 40 x 0.25 mg tablets or greater than 0.3 mg/kg in
children). Other treatments: oxygen, cardiac monitoring,
i.v. access, check electrolyte levels & correct any
imbalances. Note: diuretics that are commonly taken in patients with CHF
can cause hypokalemia which will increase digitalis
toxicity (potassium supplements should be used to correct hypokalemia).
Give atropine for unstable bradyarrhythmias or
to correct severe AV node conduction block, lidocaine for
ventricular arrhythmias (consider magnesium therapy as a temporizing antiarrhythmic
agent until Fab fragments are available). Activated charcoal or cholestyramine
can be used for acutely ingested digoxin/digitoxin; (note: gastric lavage
may intensify vagal tone & may worsen arrhythmias - pretreat with atropine;
Digibind makes gastric lavage unnecessary). Treat any hyperkalemia
>5.5 mM with Na bicarb, glucose & insulin. Kayexalate (0.5 g/kg PO)
also is helpful in binding potassium and enterohepatically-recycled digitalis,
but may cause hypokalemia when combined with glucose & insulin. |
| Major drug Interactions: verapamil,
amiodarone, quinidine can increase digoxin plasma levels (e.g. two-fold). |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Hydrocarbons
(e.g. gasoline, kerosene) |
| Source: found in homes & almost
every industrial business |
| Mechanism of Action: |
| Symptoms: odor of hydrocarbons (HCs)
on the breath or clothes, mild burning of the mouth, fever,
grunting respirations, coughing & respiratory distress,
aspiration pneumonitis, lethargy & depressed sensorium,
nausea, vomiting, diarrhea, dyspnea, sudden cardiac death due to arrhythmias.
The lungs are affected most commonly (due to aspiration). A patient who
ingests turpentine or gasoline is more likely to aspirate than a patient
who has ingested grease or petroleum jelly. Even small amounts of HCs may
cause a chemical pneumonitis; because many HCs have poor
water solubility, they penetrate deep into the bronchopulmonary tree, causing
bronchospasm followed by an inflammatory response |
| Treatment: Management for
HC ingestion is supportive. No specific antidotes are available.
Observe patients in a monitored setting for signs of respiratory distress.
Cardiac monitor and pulse oximetry are recommended. Patients who show signs
of impending respiratory failure, despite supplemental oxygen, may require
rapid intubation & ventilation. Decontamination of the GI tract generally
is not recommended because of the risk of aspiration and the low GI toxicity
of most HCs. Indicated medications include dextrose, thiamine, and naloxone
for altered mental status and albuterol for bronchospasm.Elevated aminotransferases
may be observed with HC ingestions. The halogenated HCs are particularly
hepatotoxic. |
| Notes:The American Association of
Poison Control Centers lists HCs as the 12th most common poison exposure.
In 1997, 3% of cases reported to US poison control centers involved HC exposure;
of these cases, 95% were unintentional and approximately 60% were pediatric.
More than 80% of the 1997 reported exposures were to aliphatic compounds,
such as gasoline, kerosene, and turpentine; toxic ingestions by children
younger than 5 years often involve these aliphatic HCs. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Lead |
| Source: paints, dyes. |
| Mechanism of Action: heavy metals
bind to sulfhydryl groups in proteins, resulting in alterations in enzymatic
activity. Nearly all organ systems are involved, but the nervous system,
GI, hematopoietic, renal & cardiovascular systems are most commonly
affected the most. |
| Symptoms: In children: encephalopathy
with seizures (most common). In adults: GI complaints,
neurological dysfunction and anemia are most common. Anemia. Lead
line (blue black deposit along gum margin). Wrist and/or foot drop. |
| Treatment: ABCs,
diazepam, EDTA or BAL plus EDTA. Aggressive hydration. |
| Notes: Of the heavy metals, toxicity
by chronic lead exposure is the most commonly encountered. Toxicity is more
common in lower socioeconomic areas. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: LSD (lysergic
acid dieethylamide) |
| Source: drug of abuse |
| Mechanism of Action: interacts with
several different serotonin receptor subtypes (agonist at 5-HT1A & 5-HT1C
) and antagonist at 5-HT2 (the later is believed to be not important for
producing hallucinations). |
| Symptoms: hallucinogenic (organized
visual illusions), patient may be confused or disoriented,
have distorted perceptions & impaired judgment, mydriasis,
tachycardia, mild hypertension & tachypnea,
tremor. The patient may present themselves to the ER after having
had a "bad trip" (uncomfortable hallucination). Flashbacks occur
in most patients who have taken LSD more than 10 times. Intoxication usually
lasts 8-12 hours, but psychotic behavior may persist for days. |
| Treatment: supportive care
& benzodiazepines (diazepam) to decrease agitation, haloperidol for
acute psychosis. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm,
Katzung's text. |
| Toxicon: Marijuana (cannabis,
hashish) |
| Source: usually not revealed |
| Mechanism of Action: the active ingredient
is delta-9 tetrahydrocannabinol (THC) which binds to CB1 and CB2 receptors
in the brain. |
| Symptoms: Acute: euphoria,
relaxation, subjective feelings of well-being or grandiosity, perceptual
changes (including visual distortions), drowsiness and sluggishness, diminished
coordination, paradoxical hyperalertness, a subjective sense of
slowing of the passage of time, increased appetite (the
"munchies"). Dysphoric effects can also
occur - e.g. feelings of panic, paranoia, depersonalization (a feeling that
you can step outside of yourself). Use is sometimes associated with an "amotivational
syndrome". Medically it has an effect to decrease intraoccular pressure
in glaucoma patients as well as antinausea effects which
has permited the use of marijuana (e.g. in cancer patients) in some states
in the US. |
| Treatment: supportive care.
Frequent reassurance and maintenance of a nonthreatening environment, minimal
stimuli, judicious use of benzodiazepines when significant anxiety is present |
| Notes: Marijuana remains the most
commonly used illicit drug in the United States. The 1998 National Household
Survey on Drug Abuse (NHSDA) reported that more than 72 million Americans
(33%) aged 12 years and older have tried marijuana at least once in their
lifetimes. It is a DEA category I drug (but see above). |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Methanol |
| Source: cleaning materials, solvents,
paints, varnishes, Sterno fuel, formaldehyde solutions, antifreeze, gasohol,
"moonshine," windshield washer fluid (30-40% methanol), and duplicating
fluids. |
| Mechanism of Action: A CNS depressant,
methanol is potentially toxic in amounts as small as a single mouthful.
When metabolized by hepatic alcohol and aldehyde dehydrogenase, methanol
forms formaldehyde and formic acid, both of which are toxic. The eyes, CNS,
and GI tract are affected. Formic acid is the primary toxin that accounts
for the majority of the anion gap, metabolic acidosis, and ocular toxicity.
Lactic acid also contributes to the anion gap. Formic acid inhibits cytochrome
oxidase in the fundus of the eye. Swelling of axons in the optic disc and
edema result in visual impairment. Formaldehyde has a short half-life, lasting
only minutes. Formic acid is metabolized much more slowly, and it bioaccumulates
with significant methanol ingestion. |
| Symptoms: lethargy, confusion, headache,
vertigo, blurry, nausea, vomiting, abdominal pain, indistinct, misty,
or snowstorm-like visual disturbances, blindness, coma, seizures, respiratory
depression/death. |
| Treatment: Supportive measures &
provide airway protection. Dialysis may be needed to remove
methanol and its principal toxic metabolite, formate. (While forced diuresis
might be considered, since methanol is excreted renally - dialysis works
better and has less danger of pulmonary edema, cerebral edema, or acute
respiratory distress syndrome). Attempted correction of acidosis using sodium
bicarbonate is indicated if pH is less than 7.20; note that patients
may require large quantities. An alkalemic pH makes it more likely that
formic acid will exist as its anion (formate), which cannot access the CNS
and optic nerve as readily. Administer folic acid (leucovorin)
50 mg IV every 4 hours for several days to potentiate the folate-dependent
metabolism of formic acid to carbon dioxide and water. Consider ethanol
infusion in any patient with an unexplained osmolar gap and/or
elevated anion-gap metabolic acidosis that is unaccounted for by ethanol,
until a definitive diagnosis negating its administration is made. |
| Notes: A delay in treatment of methanol
intoxication may lead to increased morbidity and mortality. Recognition
and timely treatment are essential for a full recovery. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Morphine &
similar narcotics |
| Source: narcotic analgesic, drug of abuse |
| Mechanism of Action: opioid receptor
agonist |
| Symptoms: clinical triad
of CNS depression, respiratory
depression, and pinpoint pupils (miosis) are present.
(Note: meperidine & propoxyphene sometimes are associated with mydriasis
or midpoint pupils.) Drowsiness, and euphoria are frequently seen. Hypotension
& hypothermia.The leading cause of morbidity and mortality
from pure opioid overdoses is respiratory compromise. Less
commonly, pulmonary edema, status epilepticus, and cardiotoxicity. |
| Antidote/Treatment: Administer naloxone
for significant CNS and/or respiratory depression.Naloxone can be given
IV, ET, or IM. If an IV cannot be established, administer 2 mg of IM naloxone.
By the ET, or IV route, the onset of action of naloxone is 1-2 minutes.
A second dose can be repeated every 2-3 minutes. Discontinue treatment as
soon as the desired degree of opioid reversal is achieved.The clinical half-life
of naloxone is 20-60 minutes. In patients with opiate addiction, naloxone
may precipitate opiate withdrawal symptoms, so the dose of naloxone should
be titrated carefully in such patients. Activated charcoal is the GI decontamination
method of choice for patients with opiate intoxication following ingestion.
Because of impairment of gastric emptying and GI motility produced by opiate
intoxication, activated charcoal still may be effective when patients present
late following ingestion. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon:Organophosphate
& carbamate (anticholinesterases) |
| Source: pesticides, chemical warfare |
| Mechanism of Action: Organophosphates
irreversibly bind to cholinesterase, causing the phosphorylation and inactivation
of acetylcholinesterase. Carbamate poisoning exhibits a similar clinical
picture to organophosphate toxicity. However, unlike organophosphates, carbamate
compounds temporarily bind cholinesterase for approximately 6 hours with
no permanent damage. Carbamates have poor CNS penetration and cause minimal
CNS symptoms. |
| Symptoms: Mild flulike symptoms from
minimal exposures frequently are unreported or untreated. Common presenting
features include: headache, mental confusion, diffuse muscle
cramping and/or fasiculations, miosis, bronchospasm,
weakness, excessive secretions, nausea,
vomiting, and diarrhea (remember: SLUDE).
The condition may progress to seizure, coma, paralysis, respiratory
failure, and fatality. Delayed or inadequate treatment of organophosphate
poisoning can lead to prolonged (months) or permanent neurotoxic symptoms.
|
| Antidote/Treatment: decontamination,
atropine, oxygen, pralidoxime for organophosphates (not
carbamates); benzodiazepines to control seizures. |
| Notes: In the US: Approximately 20,000
reported organophosphate exposures occur each year. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Oxalate plant
poisoning |
| Source: caladium, philodendron, calla
lily, skunk cabbage, and others |
| Mechanism of Action: Nonsoluble calcium
oxalate crystals are found in plant stems, roots, and leaves. These needlelike
crystals produce pain and edema when they contact lips, tongue, oral mucosa,
conjunctiva, or skin. Edema primarily is due to direct trauma from the needlelike
crystals and, to a lesser extent, by other plant toxins (eg, bradykinins,
enzymes). |
| Symptoms: Depending on the mode of
contact (skin, eye or oral): local skin erythema and/or edema (typical of
a contact dermatitis) due to contact with plant sap or
juices. Keratoconjunctivitis and corneal abrasions after contact with plant
material, edema, erythema, bullae, and local inflammation
of mouth and oral mucosa after contact; esophagitis, slurred or unintelligible
speech, laryngeal edema (with sufficient contact), superficial necrosis
developing days after initial contact. |
| Treatment: Decontaminate mouth, eye,
and skin by physically removing all plant material. Treat eye and skin exposure
with copious water irrigation. Acetaminophen
for pain control. Antihistamines (diphenhydramine). |
| Notes: Plant exposures are some of
the most frequent poisonings reported to poison control centers. Exposures
to plants containing oxalate crystals, such as Philodendron and Dieffenbachia,
are among the most common toxic plant exposures reported in the US. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Phencyclidine
(PCP, angel dust) |
| Source: drug of abuse, dissociative
anesthetic |
| Mechanism of Action: a NMDA (Glutamate)
receptor antagonist. It is primarily metabolized in the liver and undergoes
significant enterohepatic recirculation. Clinical effects occur within minutes
and can last several hours. |
| Symptoms:The presentation of the
acutely poisoned PCP patient may range from catatonia to extreme agitation.
Horizontal, vertical, or rotary nystagmus is usually present
(>50%). Miosis with a blank stare, hypertension, tachycardia,
disorientation, amnesia, analgesia, combativeness
& paranoid behavior, catatonic posturing,
hyperreflexia, muscle rigidity, dystonia, hallucinations,
coma . |
| Treatment: ABCs, IV hydration
and sedation are initial management considerations. Administer
benzodiazepines (diazepam) to patients with severe agitation,
with or without antipsychotics (haloperidol) to treat prlonged
psychotic behavior. (Note: Because of the anticholinergic effects of PCP,
neuoleptics with anticholinergic effects, such as chlorpromazine should
be avoided.) Physical and chemical restraints may be necessary.
Activated charcoal minimizes the enterohepatic circulation
of the drug. PCP coma may last 7-10 days |
| Notes: Acute phencyclidine (PCP) intoxication
can be one of the most challenging toxicologic emergencies for the emergency
physician. The myriad of presentations may range from a "bad trip"
to seizures and coma. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm,
Katzung's text, Goodman & Gilman's text |
| Toxicon: Phenothiazines |
| Source: antipsychotic medication (e.g.
chlorpromazine) |
| Mechanism of Action: "Anti-transmitter"
actions: block histamine, serotonin, norepinephrine and dopamine receptors.
Block of alpha-adrenergic receptors. |
| Symptoms: drowsiness, agitation,
convulsions, muscle spasms, tremor & rigidity, inability
to sit still, miosis, orthostatic hypotension and hypothermia
(poikliothermia), ventricular tachyarrhythmias,
coma |
| Treatment: gastric lavage
(even if several hours have elapsed since the drug was taken - these drugs
decrease GI motility). Activated charcoal binds most phenothiazines,
and may be followed by a saline cathartic. Hypotension often responds to
fluid replacement. If a pressor agent is required, norepinephrine or dopamine
is prefered over epinephrine due to the concern about the "epi reversal"
effect on blood pressure (unopposed beta-2 effect in the presence of alpha
receptor blockade by the phenothiazine). Seizures may be treated with diazepam
or phenytoin. |
| Reference: Katzung's text |
| Toxicon: Phenytoin |
| Source: anticonvulsant |
| Mechanism of Action: sodium channel
blocker, decreases neuronal excitability. |
| Symptoms: nystagmus (horizontal,
vertical), ataxia, slurred speech, lethargy & confusion,
coma & seizures, hypotension. Chronic side effects:
gingival hyperplasia, hirsutism (excessive
hairiness), rashes, acne. |
| Treatment: ABCs. Activated charcoal.
Hemodialysis or hemoperfusion are ineffective for enhancing elimination.
Benzodiazepine for seizures. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon: Salicylates |
| Source: aspirin |
| Mechanism of Action: Salicylates cause
an uncoupling of oxidative phosphorylation. Catabolism occurs secondary
to the inhibition of ATP-dependent reactions with the following results:
increased oxygen consumption,increased carbon dioxide production, accelerated
activity of the glycolytic and lipolytic pathways, depletion of hepatic
glycogen,hyperpyrexia. |
| Symptoms: Acid-base disturbances
vary with the severity of toxicity. Initially, hyperventilation
a respiratory alkalosis develops secondary to direct stimulation
of the respiratory centers. This may be the only consequence of mild salicylism.
A severe metabolic (ketolactic) acidosis with
compensatory respiratory alkalosis may develop with severe salicylate intoxication.
Potassium moves from the intracellular space to the extracellular space.
Excretion of hydrogen ions produces acidic urine. A paradoxical
aciduria (hydrogen ion excretion) occurs with the depletion of sodium bicarbonate
and potassium. Ototoxicity, tinnitus, tachycardia, CNS depression,
seizures, nausea & vomiting, GI hemorrhage, prolonged
bleeding time, dehydration. |
Treatment: ABCs.
Endotracheal intubation may be required. Gastric lavage
may be beneficial, unless contraindicated, up to 60 minutes after salicylate
ingestion.
Administer activated charcoal unless contraindications
are present. Provide treatment for correction of fluid deficits and enhancement
of excretion and elimination. Hemodialysis is the best
method for enhanced elimination. Sodium bicarbonate to
alkalinize the urine & increase salicylate excretion. Monitor
glucose levels closely. Initial hyperglycemia may give way to hypoglycemia
and worsening CNS symptoms. |
| Notes: Onset of chronic salicylism
may be insidious; elderly individuals may consume an increasing amount over
several days to alleviate arthralgias, subsequently becoming confused because
salicylate pharmacokinetics change at higher concentrations. This may lead
to a perpetual spiral of increased salicylate consumption and increased
confusion. Similar scenarios occur in persons with underlying psychiatric
disorders |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Toxicon:Theophylline |
| Source: medication for asthma &
COPD |
| Mechanism of Action: Theophylline
affects the cardiovascular (CV), neurological, GI, and metabolic systems.
Hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia, and acidosis
commonly occur after an acute overdose. Medication, diet, and underlying
diseases can alter its narrow therapeutic window. Adverse effects can be
evident at therapeutic serum levels. |
| Symptoms: nausea, vomiting, abdominal
pain, mild metabolic acidosis, hypokalemia, hypophosphatemia, hypomagnesemia,
hyperglycemia, sinus tachycardia, tremors,
seizures, hypotension, and significant
dysrhythmias. |
| Treatment: ABCs. Aggressive gut decontamination
with repeated doses of activated charcoal & whole bowel
irrigation. Propranolol or other beta blockers
can block a beta-mediated sinus tachycardia & hypotension. Phenobarbital
is prefered over phenytoin for treatment of convulsions; most anticonvulsants
are ineffective. Hemodialysis is indicated for serum levels
>100mg/L and for intractable seizures. |
| Notes: |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm,
Katzung's text |
| Toxicon: Tricyclic antidepressants |
| Source: Classical antidepressant |
| Mechanism of Action: TCAs affect the
cardiovascular, central nervous, pulmonary, and gastrointestinal systems.
The toxic effects on the myocardium are related to the blocking of fast
sodium channels, which involves the same mechanism as type IA antiarrhythmics
(eg, quinidine). CNS toxicity results from the anticholinergic effects and
direct inhibition of biogenic amine reuptake. |
| Symptoms: tachycardia, hypotension, confusion
or hallucinations, mydriasis, dry mucous membranes and skin, decreased bowel
sounds, urinary retention, seizures, QRS prolongation & arrhythmias. |
| Antidote/Treatment: ABCs, activated
charcoal to prevent further absorption, sodium
bicarbonate (a 1st line thereapy if QRS >100 ms, seizures,
acidosis or arrhythmias are present; alkalemia has been shown to protect
against and treat dysrhythmias), benzodiazepines (lorazepam)
for seizures. Intubate and hyperventilate if coma or depressed
mental status is present. Perform orogastric lavage if ingestion is known
to be lethal (after intubation). |
| Notes: In the US: Approximately 500,000
cases of TCA toxicity per year are reported. Fatality
before reaching a healthcare facility occurs in approximately 70% of patients
attempting suicide with TCAs. Tricyclic antidepressants are the
number one cause of fatality from drug ingestion. Only 2-3% of
TCA overdoses that reach a health care facility result in death. |
| Reference: http://www.emedicine.com/emerg/toxicolgy.htm |
| Drug: EDTA (ethylene
diamine tetra acetic acid) |
| Drug Class: Heavy Metal Chelator |
| Mechanism of Action: used as a disodium
calcium salt. Forms a soluble heavy metal chelate in the blood which is
excreted through the urine. |
| Indications: chelator for lead (Pb)
& cadmium (Cd). Used in combination with BAL when lead levels are >70
ug/dl |
| Contraindications: Anuria. Ventricular
arrhythmias. Use during pregnancy only if the benefits clearly outweigh
the risks. Use with extreme caution in digitalized clients as EDTA and calcium
may reverse the desired effect of digitalis. Use with caution in clients
with heart disease (e.g., CHF) or hypokalemia. |
| Side Effects: Electrolyte imbalance
including hypocalcemia, hypokalemia, hypomagnesemia, hyperuricemia may occur
during treatment. |
| Pharmacokinetics: administered i.v. |
| Reference: http://www.healthdigest.org/drugs/ |
| Drug: Penicillamine
(Cuprimine ®) & N-acetylpenicillamine
(NAP) |
| Drug Class: Heavy Metal Chelator |
| Mechanism of Action: chelating agent
recommended for the removal of excess copper (e.g.in patients with Wilson's
disease). |
| Indications: NAP - primary drug of
choice for methyl mercury & copper poisoning. Penicillamine - secondary
agent for treatment of copper & arsenic poisoning. |
| Side Effects: Penicillamine - generalized
pruritus, early & late rashes |
| Pharmacokinetics: penicillamine is
absorbed rapidly but incompletely (40-70%) from the gastrointestinal tract,
with wide inter-individual variations. Food, antacids, and iron reduce absorption
of the drug. The peak plasma concentration of penicillamine occurs 1-3 hours
after ingestion; i |
| Reference: www.rxlist.com |
| Drug: Succimer (Chemet
® ) |
| Drug Class: Heavy Metal Chelator |
| Mechanism of Action: metal chelating
agent |
| Indications: Secondary drug to BAL
& EDTA for use in the treatment of acute lead poisoning, to remove excess
lead from the body, especially in small children. Used when lead concentration
is > 45 ug/dl. |
| Side Effects: skin rash, nausea, diarrhea |
| Pharmacokinetics: can be administered
orally. |
| Reference: http://www.nlm.nih.gov/medlineplus/druginfo/ |
| Drug: Dimercaprol (BAL
in oil) |
| Drug Class: Heavy Metal Chleator |
| Mechanism of Action: Forms a chelate
by binding sulfhydryl groups with arsenic, mercury, lead, and gold, thus
increasing both urinary and fecal excretion of the metals. |
| Indications: Acute arsenic, mercury,
and gold poisoning. With EDTA in acute lead poisoning. Not effective for
chronic mercury poisoning. |
| Contraindications: Iron, cadmium,
silver, uranium, or selenium poisoning. Hepatic or renal insufficiency,
except postarsenical jaundice. Use during pregnancy only if poisoning is
life-threatening. |
| Side Effects: Most common include
hypertension and tachycardia (dose dependent) |
| Pharmacokinetics: Administered deep
IM only. To be fully effective, administer 1-2 hr after exposure. Peak plasma
concentration: IM, 30-60 min. Mostly distributed to extracellular fluid.
Time to peak levels: 30-60 min. Rapidly metabolized to inactive product
and completely excreted in urine and feces in 4 hr. |
| Major drug Interactions: |
| Reference: http://www.healthdigest.org/drugs/ |
| Drug: Deferoxamine
(Desferal ® ) |
| Drug Class: Iron chelator |
| Mechanism of Action: an iron-chelating
agent. Desferal chelates iron by forming a stable complex that prevents
the iron from entering into further chemical reactions. It readily chelates
iron from ferritin and hemosiderin but not readily from transferrin; it
does not combine with the iron from cytochromes and hemoglobin. Desferal
does not cause any demonstrable increase in the excretion of electrolytes
or trace metals. |
| Indications: Desferal is indicated
for the treatment of acute iron intoxication and of chronic iron overload
due to transfusion-dependent anemias. |
| Contraindications: Desferal is contraindicated
in patients with severe renal disease or anuria, since the drug and the
iron chelate are excreted primarily by the kidney. |
| Side Effects: Fever, urticaria, rash.
At injection site - localized irritation, pain, burning, swelling. |
| Pharmacokinetics: available in vials
for intramuscular, subcutaneous, and intravenous administration. Desferal
is metabolized principally by plasma enzymes, but the pathways have not
yet been defined. The chelate is readily soluble in water and passes easily
through the kidney, giving the urine a characteristic reddish color. Some
is also excreted in the feces via the bile. |
| Reference: www.rxlist.com |
Mechanisms:
Drug interactions
can be either pharmacodynamic or pharmacokinetic in nature. Pharmacodynamic
interactions typically result in additive or synergistic increases in
drug effects & toxicity. Most drug interactions are pharmacokinetic
and can result from alterations in absorption, protein-binding effects,
changes in drug metabolism, or alterations in elimination.
Two major players in many pharmcokinetic
drug interactions are different isozymes of cytochrome P450 (CYP) &
p-glycoprotein (PGP). CYP isozymes can either be inhibited or induced
by drugs, resulting in drug-drug interactions for drugs metabolized by
CYP.
- CYP3A4 is the most prodominant CYP in the liver
(50% of total activity). High affinity substrates include simvastatin,
lovastatin, cyclosporine & verapamil & act as competitive inhibitors.
- CYP2D6, 2C9 & 2C19 exhibit
a bimodal distribution of activity because of the inheritance of inactivating
mutations
- 10% of caucasians are CYP2D6 poor
metabolizers (homozygous for mutant alleles) & have a 10-fold reduced
metabolic efficiency. They can have 10-fold higher steady-state drug
levels. CYP2D6 metabolizes beta blockers & antiarrhythmics.
- In the gut, PGP pumps drug into
the lumen and thereby limits drug absorption.
- In the kidney, PGP pumps drug into
the renal tubular lumen (urine).
- In the brain, PGP eliminates drug
from the CNS.
- PGP can be competitively inhibited
by drugs (e.g. cyclosporin A, quinidine, verapamil, itraconazole, clarithromycin),
or have its levels induced (rifampin).
|
| Reference: Katzung's text, Dr. Dreisbach's
handout |
| Drug: Digoxin
(Lanoxin ®) |
| Drug Class:Cardiac glycoside (positive inotrope)
|
Properties Promoting Drug Interaction:
- Digoxin is susceptible to inhibition of its GI
absorption.
- Digoxin toxicity may be increased by drug-induced
electrolyte imbalances (e.g. hypokalemia).
- Renal excretion of digoxin is susceptible to inhibition.
|
Drugs that may increase digitalis effect:
- Amiodarone, Verapamil,
Itraconazole Erythromycin &
Clarithromycin: inhibit renal
digoxin excretion via p-glycoprotein. Increased plasma digoxin levels.
- Potassium-depleting
drugs: increased likelihood of digoxin toxicity
- Quinidine:
displacement from tissue binding sites & reduced renal digoxin excretion
via p-glycoprotein. Plasma digoxin levels will double immediately due
to acute reduction of digoxin Vd by 50% (displacement from tissue binding
sites), and steady state levels will double because of reduced digoxin
clearance.
|
Drugs that may decrease digoxin effect:
- Rifampin
is the strongest inducer of both cyt P450 & p-glycoprotein &
will reduce plasma digoxin levels primarily by inducing intestinal p-glycoprotein.
P-glycoprotein acts to reduce drug absorption in the GI tract by pumping
drug back into the GI lumen.
- St. John's wort:
St. John's wort is a potent p-glycoprotein inducer that will increase
digoxin's renal clearance & reduce intestinal absorption of digoxin.
Induction may take 2-4 weeks to develop & may persist for 2-4 weeks
after the inducer is stopped.
|
| Reference: Katzung's text & http://www.healthdigest.org/drugs/rifampin.html |
| Drug: Quinidine
(generic) |
| Drug Class: Antiarrhythmic, Antimalarial |
Properties Promoting Drug Interaction:
- Metabolism is inducible
- Quinidine is a potent inhibitor of CYP2D6. It will
conver a rapid metabolizer to a slow metabolizer phenotype. This is
the same isozyme inhibited by fluoxetine, etc.
- Renal excretion is susceptible to changes in urine
pH
- Renal excretion occurs via p-glycoprotein &
can antagonize elimination of other drugs
- additive effects with other agents that prolong
the QTc interval
|
Drug Interactions:
- Drugs that alkalinize
the urine (Acetazolamide, Na bicarbonate, Carbonic Anhydrase Inhibitors):
decreases renal excretion & elevate plasma quinidine levels.
- Cimetidine:
cimetidine is a potent inhibitor of all clinically relevant CYP isozymes
and p-glycoprotein. Avoid use with amiodarone, digoxin & warfarin.
- Digoxin:
quinidine displaces digoxin from tissue binding sites & inhibits
p-glycoprotein mediated renal excretion
- Drugs that prolong
the QTc interval: additive effects to prolong the QTc
and cause cardiac arrhythmias (torsade de pointes)
- Rifampin:
increases hepatic metabolism of quinidine
|
| Reference: Katzung's text |
| Drug:Warfarin
(Coumadin ®)
|
| Drug Class: Anticoagulant |
Properties Promoting Drug Interaction:
- Metabolized by CYP2C9 isozyme (which can be induced
or inhibited by other drugs)
- Binding to plasma proteins (can be reduced by other
drugs)
- Action to inhibit synthesis of Vit K dependent
clotting factors (can be antagonized or increased by other drugs &
conditions)
- Vit K producing bacteria in the gut can be eliminated
by antibiotics
- Anticoagulant effects can be altered with other
drugs
|
Drugs that may increase warfarin effect:
- Phenylbutazone
& Sulfinpyrazone
: inhibit platelet function, inhibit warfarin metabolism of S-warfarin
& displace warfarin from albumin (these drugs are not commonly used).
- Metronidazole,
Fluconazole &
Trimethoprim-Sulfamethoxazole
: inhibit metabolism of S-warfarin
- Aspirin, hepatic
disease, heparin, hyperthyroidism: increase warfarin
effect pharmacodynamically
- Third generation
Cephalosporins : eliminate bacteria in GI tract produce
Vit K & inhibit Vit K expoxide reductase.
|
Drugs that may decrease warfarin effect:
- Vitamin K:
increased synthesis of clotting factors
- Chlorthalidone
& Spironolactone:
increased synthesis of clotting factors
- Hypothyroidism:
decreased turnover of clotting factors.
|
| Reference: Katzung's text |
| Drug: St.
John's wort |
| Drug Class: herb (antidepressant) |
Properties Promoting Drug Interaction:
- potent PGP inducer
- CYP 3A4 inducer
- inhibition of reuptake of amines (pharmacodynamic
interaction)
|
Drug Interactions:
- HIV protease inhibitors,
NNRTIs, warfarin, oral contraceptives, anticonvulsants, digoxin, theophylline,
cyclosporin, etc.: accelerated metabolism
and lower plasma levels
- Antidepressants,
MAOIs, Stimulants: Serotonergic crisis
|
| Reference: Katzung's text |
