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University of Kentucky
College of Pharmacy
Pharmacotherapy (PPS 946)
Frank Romanelli, Pharm.D., MPH, BCPS
“Introduction to Toxicologic Principles”
KENTUCKY REGIONAL POISON CONTROL CENTER
LOUISVILLE, KY
1-800-722-5725
Epidemiology
 Four to five million cases of poisoning in the US annually.
 About 2 million exposures are reported to poison control centers (PCC).
 Average time to presentation following a toxic ingestion:
Adult – 3.5h
Child – 1.5h
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Children less then 17 years of age account for the most ingestions but only 10% of
fatalities.
Fatalities in children less then the age of 6 are uncommon (4%).
Since the 1960’s fatalities in children have been decreasing.
Childhood ingestions are usually single, known, and promptly recognized.
Most commonly ingested products in children (nationally):
Plants
Cleaning products
Cough/cold preps
Perfumes/colognes
In adolescents and adults, toxic ingestions usually represent substance abuse or
suicide attempts.
Adult/adolescent ingestions are usually multiple, intentional, unknown, and with
delayed recognition.
In the elderly, toxic ingestions usually result from chronic overmedication
(polypharmacy).
Potential Routes of Toxic Exposure
 Ingestion – 75%
 Dermal – 8%
 Inhalation – 7%
 Ocular – 6%
 Bites and stings – 4%
Basic Approach to the Patient
 Identify the substance, amount, and route of ingestion.
 Always assume worse case scenario.
 In cases involving children, if the toxin is unknown identify all medications
(including OTCs) and household products in the vicinity and those taken by
caretakers and relatives.
 Physical exam:
Vital Signs
Coma grade/level of consciousness
Neurologic findings – seizures, nystagmus, miosis (cholinergics), mydriasis
(anticholinergics), fixed dilated pupils
Cardiac - dysrhythmias
Odors
 Think TOXIDROMES- a constellation of signs and symptoms referrable to a single
drug overdose.
Lab Assessment
 Electrolytes
Anion gap
 Blood gases
 Serum osmolality
 EKG
 Toxic screen
 Other more secondary tests:
Coag profile
CPK (creatine phosphokinase)
LFTs
U/A
Serum myoglobin
KUB
Treatment Principals
 Provide supportive care
 Prevent absorption
 Enhance elimination
 Interrupt or alter metabolism
 Provide specific antidotes
Initial Management
 Initial stabilization involves the ABC’s
Airway
Breathing
Circulation
Drugs
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Adult tox drug cocktail:
Thiamine 100mg (IV)
D5W – 50ml (IV)
Naloxone – 2-8mg IV
Flumazenil – 0.2mg IV
After initial management interrupt any type of ongoing toxic exposure.
Syrup of Ipecac
 Plant derivitive which contains emetine and cephalin. These compounds responsible
for the emetic effect.
 Local gastric irritant and stimulator of the CTZ.
 A lack of prospective studies on the clinical outcome of decontamination measures
and the lack of efficacy of syrup of ipecac in pharmacologic studies beyond 60-90
minutes post-ingestion have resulted in the increased use of activated charcoal as an
alternative to syrup of ipecac.
 Administration of syrup of ipecac is recommended for alert patients who would
benefit from emesis and have no contraindications.
 The use of emesis to eliminate ingestions beyond 4-6h of time 0 is usually ineffective
unless the toxin itself delays absorption time.
 6-12 months – 5-10cc followed by 10-20cc/kg water; repeat X1 if no vomiting in 20
min.
 1-12 years – 15cc followed by 10-20cc water; repeat X1 if no vomiting in 20min.
 Adults – 15-30cc followed by 200-300cc of water; repeat X1 if no vomiting in 20
min.
 Relative contraindication:
Seizure inducing drugs
Rapid coma inducing drugs
Pregnancy
Hydrocarbons
Severe bradycardia
 Absolute contraindication:
Children < 6 months of age
Seizing or comatose patients
Corrosive substances
Gastric Lavage
 Gastric lavage is the passage of a large bore orogastric tube and the sequential
administration and aspiration of small volumes of liquid (200-300cc of warm water or
saline) for removal of gastric contents. Avoid using water in children – only saline
due to risk of hyponatremia. Lavage should be continued until the aspirate is clear.
Follow-up with the installation of activated charcoal.
 A prospective controlled study of acutely self-poisoned patients indicated that little
clinical deterioration occurs in asymptomatic patients treated without gastric
emptying; in fact gastric lavage was associated with a higher incidence of aspiration
pneumonia.
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If carried out within one hour of ingestion has been shown to be more effective then
syrup of ipecac.
AACT supports the use of gastric lavage only in cases where the ingestion occurred
one hour prior.
Unprotected airway is an absolute contraindication.
Hydrocarbons and corrosives considered to be a relative contraindication.
Aspiration pneumonia and bradycardia most common complications.
Activated Charcoal
 Emerging as the sole decontamination procedure..
 Now available OTC.
 Administer cautiously in patients with ileus. Check for presence of bowel sounds.
 Adsorbs toxic substances thus preventing their absorption via the GI tract.
 Charcoal is pressed under high pressure to yield extensive surface area for adsorption
of chemicals.
 Most common adverse effect is constipation – thus formulated with sorbitol.
 1-12 years old
1-2gm/kg/dose (do not use sorbitol containing product more then
1-2X per day)
 Adults
30-100gm
 Not effective for:
Cyanide
Organic solvents
Iron
Alcohols (ethanol, methanol)
Lithium
Minerals
 Charcoal will adsorb ipecac, always use ipecac first.
 Stool will turn black.
 Available as powder, liquid, or capsules.
Cathartics
 Two types of cathartics: saline (Mg) and saccharides (sorbitol).
 Cathartics may enhance drug removal but have never been shown to decrease
morbidity/mortality or reduce hospital stay.
 Contraindicated in the ingestion of corrosives.
 Magnesium citrate – 4ml/kg max 300cc
 Sorbitol 70% - 2ml/kg, max 75-150ml
 Magnesium sulfate – 250mg/kg, max 30gm
 Whole bowel irrigation
Useful and rapid means of emptying the gut in 4 to 6 hours. Can be messy and labor
intensive. Most often carried out with polyethylene glycol (PEG) AKA GoLytley®.
PEG is more effective at purging the entire gut versus stimulating defecation only.
Most often used in the massive ingestion of toxic substances in patients presenting
late (>4h post-exposure); ingestion of SR drug products; ingestion of drug packets by
body stuffers; ingestion of small foreign bodies (disk batteries); and ingestion of
substances not removed by activated charcoal. Procedure involves infusion either
orally or by orogastric tube of PEG until the rectal effluent is similar in appearance to
the infusate.
Peritoneal dialysis
 Often used in the management of patients with renal failure.
 Almost never used in the treatment of toxic ingestions.
 Slow procedure which can be carried out over 24 hours.
 Does not require anticoagulation or extensive equipment.
 Toxins diffuse across the mesenteric capillaries and the peritoneal membrane into
dialysate which is dwelling within the peritoneal cavity.
 Not ideal for the removal of toxins.
Hemofiltration
 Similar procedure to hemodialysis although blood is pumped through a hemofilter.
 Hemofiltration offers the advantage over hemodialysis that toxins with larger
molecular weights (e.g., aminoglycosides, metals) can be removed.
Highly protein bound toxins are also more rapidly removed by hemofiltration versus
hemodialysis
Antidotes
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Naloxone
Diphenhydramine
Desferroxamine
Dimercaprol (BAL)
N-acetylcysteine (Mucomyst®)
Glucagon
Methylene blue
Pralidoxime
CaNa2EDTA
Sodium Thiosulfate
Ethanol
Pyridoxine
Phentolamine
University of Kentucky
College of Pharmacy
Pharmacotherapy PPS 946
Frank Romanelli, Pharm.D., MPH, BCPS
“Introduction to Toxologic Principles”
GOAL
To introduce concepts and theories of toxicology and management principals related to
patients presenting following toxic ingestions.
Learning Objectives
Upon completion of this lecture the learner should be able to:
1.
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4.
Describe the differences between typical childhood and adolescent toxic ingestions.
List the most commonly ingested toxic substances in children.
List the most common route of toxic ingestion.
Describe the factors which should be considered when approaching a patient with a
history of toxic ingestion.
5. List the 5 treatment principals involved in managing toxic ingestions.
6. Describe the advantages and disadvantages of each of the following procedures or
medications:
Syrup of ipecac
Gastric lavage
Activated charcoal
Cathartics
Dialysis
7. When presented with a patient oriented case, formulate a management strategy
including the administration of an antidote for a specific intoxication.