SALICYLATES

I. BACKGROUND infant or it may be short-lived. The most common

Salicylates are a group of compounds derived from
salicylic acid to which an ester or salt is added. Aspirin
(acetylsalicylic acid) is one of the most commonly used
therapeutic salicylates, both in pure form and in
combination with other drugs.
It is considered that Aspirin is the most common cause of
salicylate poisoning but there are several compounds that
can cause similar toxic manifestations. Methyl salicylate
(oil of wintergreen), generally meant for topical application,
causes a disproportionately high number of salicylate
poisoning deaths when ingested or used topically in
excess. The severe toxicity of this agent is related to its
high salicylate content. A potentially lethal dose for a 2-
year-old child is one teaspoon (5 cc) containing the
equivalent of 6.9 grams of aspirin or almost 22 adult
aspirin tablets. Bismuth subsalicylate (Pepto Bismol), an
over-the-counter preparation containing up to 236 mg/15
mL of salicylate, is used in the treatment of diarrhea and
prophylaxis for traveler's diarrhea.
presentation for a child is metabolic acidosis.
Although historically aspirin has been the most common
cause of poisoning and death in children younger than 5
years of age due to its association with Reye’s syndrome,
the incidence of salicylate overdose during the past two
decades has significantly decreased. Poison control
surveillance data now rank salicylate poisoning as the
13th most common fatal ingestion. This decrease may be
due to the fact that pediatricians currently prefer
acetaminophen/ibuprofen preparations, and the FDA
limits baby ASA bottles to 36 tablets per bottle and
mandates child-resistant caps. It is estimated that the use
of child-resistant packaging for salicylate-containing
medications has resulted in a 34% reduction in the
salicylate-related child mortality rate.
II. CHEMISTRY

Basic Pharmacology
Aspirin is rapidly absorbed after oral administration. Nearly Common Name: Acetylsalicylic Acid
the full dose of acetylsalicylic acid is hydrolyzed to salicylic IUPAC Name: 2-acetoxybenzoic acid
acid, the bioactive form of the drug. Peak plasma Molecular Formula: C9H8O4
concentrations of salicylates are reached about 2 hours
ASPIRIN
after ingestion of a therapeutic dose of aspirin. The plasma
half-life of aspirin is between 13 and 20 minutes, while III. MECHANISM OF TOXICITY
that of salicylic acid is dose dependent. If the dose is less 1. Respiratory center stimulation
than 3 grams, the half-life is about 2-4 hours, and in larger hyperventilation respiratory alkalosis
doses the half-life may be extended up to 19 hours. Large renal HCO3 elimination
overdoses of aspirin can cause a large tablet mass or ↑ osmotic diuresis
bezoar in the stomach. This delays absorption and plasma 2. Uncoupling of Oxidative Phosphorylation
salicylate levels continue to rise over 20 hours or more. – metabolic acidosis
– ↑ fluid loss
Epidemiology – ↑ heat production
Occurrence in the United States – hypoglycemia
According to the American Association of Poison Control 3. Inhibition of tricarboxylic acid cycle
Centers' National Poison Data System, 10,243 single – metabolic acidosis
exposures to acetylsalicylic acid, alone or in combination 4. Enhancement of protein metabolism and inhibition
with other drugs, were reported in 2016, along with 6573
single exposures to methyl salicylate. About 4,500 of these of amino acid metabolism
exposures were intentional. Almost 200 exposures – metabolic acidosis
resulted in major outcomes, and 22 fatal cases were – aminoaciduria – osmotic diuresis
noted. 5. Stimulation of gluconeogenesis
– hyperglycemia
Age-related demographics – glycosuria – osmotic diuresis
Generally, the degree of the toxicity is more severe in
6. Stimulation of lipid metabolism
elderly individuals and infants, as well as in persons with
coexisting morbidity or chronic intoxication. – metabolic acidosis (ketoacidosis)
– ketonuria – osmotic diuresis
Acid-base disturbances vary with age and severity of the 7. Increased pulmonary capillary permeability
intoxication. Infants rarely present with pure respiratory – pulmonary edema
alkalosis. Respiratory alkalosis may not develop in an
IV. CLINICAL TOXICOLOGY  keep urine pH >7.5
Haemodialysis
1. Assessment  prevent and treat salicylate
Assessment of ACUTE salicylate intoxication based induced end-organ injury
on dose ingestion
Ingested Dose (mg/kg) Estimated Severity
ANTIDOTE
< 150 No toxic reaction expected - no specific antidote
– Urine alkalinization with sodium
150-300 Mild to moderate toxic reaction bicarbonate to prevent acidemia and
300-500 Serious toxic reaction promote salicylate elimination
– Mechanism: Ion trapping
>500 Potentially lethal Dose: 150 mEq/L in D5W IV at 100-200 mL/h
– Or 3 amps in 1 L D5W at 1-2x maintenance
2. Clinical Manifestations rate
Acute ingestion Goal: Urine pH 7.5 – 8
 Vomiting Monitoring: Do not let serum pH exceed 7.55
 Hyperpnea
 Tinnitus V. RELATED POISONS
 Lethargy Willow bark (Salix alba vulgaris)
 Respiratory alkalemia  chew on the bark to reduce fever and inflammation
 Metabolic acidosis  contains salicin
Chronic intoxication Aspen bark (Populus tremuloides)
 Dehydration  same Saliceae family with Willow Bark
 Pulmonary edema  lung conditions
 can be used interchangeably with willow
 Coma
Birch bark (Betula spp)
 Seizures  similar salicylate constituents to willow and aspen
 Hypoglycemia  genitourinary tract
 Hyperthermia  source of betulinic acid (potential antineoplastic
compound)
3. Diagnosis Willow bark (Salix alba vulgaris)
If poisoning is suspected, measure: Acacia (flower oil)
Calycanthus (leaves)
 serum salicylate level (drawn at Camellia (leaves)
least a few hours after ingestion)
 urine pH
 arterial blood gas VI. BIBLIOGRAPHY
 serum electrolytes
1) Aspirin Overdose. (January 16, 2011). Retrieved March 10,2018,
 serum creatinine from https://www.ahcmedia.com/articles/129502-aspirin-overdose
 plasma glucose
2) Kwong, T. C. (2013). The clinical toxicology laboratory: contemporary
 blood urea nitrogen practice of poisoning evaluation (2nd ed.). Washington, DC: AACC Press.

4. Management 3) Haddad, L. M., Winchester, J. F., Shannon, M. W., Borron, S. W., &
Burns, M. J. (2007). Haddad and Winchesters clinical management of
A. Emergency and supportive measures poisoning and drug overdose (4th ed.). Filadelfia, PA: Saunders.
 maintain airway
 assist ventilation 4) Salicylates in Salix, Populus and Betula. (2006, February 15).
Retrieved March 12, 2018, from http://ndnr.com/pain-
 administer supplemental oxygen medicine/salicylates-in-salix-populus-and-betula/
 establish intravenous access
B. Gastrointestinal Decontamination 5) Willow bark. (n.d.). Retrieved March 12, 2018, from
Activated charcoal 1g/kg. https://www.umm.edu/health/medical/altmed/herb/willow-bark
 massive overdose
6) Pillay, V.V. Modern medical toxicology: completely updated, revised
 every 4 hours for 24 hours and profusely illustrated. 4th ed., Jaypee Brothers Medical Publishers,
C. Enhanced Elimination 2013.
Urinary and Serum Alkalinization
 IV bicarbonate infusion 7) Salicylate Toxicity. (2017, December 20). Retrieved March 17, 2018,
from https://emedicine.medscape.com/article/1009987-overview#a6
1mmol/kg/hr,
 after initial slow bolus of 2mmol/kg
VII. QUIZ QUESTIONS

A. Identification
1. This mechanism of toxicity resulted to ↑ heat production
2. Parent compound of Aspirin
3. Prevents salicylate induced end-organ injury
4. IUPAC name of Aspirin
5. Serious toxic reaction dose

B. True or False

_______1. <150 mg/kg dose is considered to be mild to moderate reaction.

_______2. Activated charcoal is used to enhance elimination of Aspirin.
_______3. Bismuth salicylate is also known as oil of wintergreen.
_______4. Hyperventilation leads to metabolic acidosis.
_______5. Tachypnea can be associated in severe salicylate poisoning

C. Multiple Choice

1. What is generally held to be the nearest thing to a direct antidote for salicylate poisoning?
A. Haemodialysis B. Urinary alkalinization
C. Activated charcoal D. Bismuth subsalicylate

2. Emergency and supportive measures for salicylate poisoning, except:

A. supplemental oxygen B. ventilation
C. maintain airway D. subcutaneous access

3. All of the following may be seen in salicylate poisoning except:

A. Hyperglycemia B. Tinnitus
C. Seizures D. Respiratory alkalosis

4. Pepto Bismol is the brand name for:

A. Bismuth salicylate B. Methyl salicylate
C. Oil of wintergreen D. Bismuth subsalicylate

5.Direct stimulation of respiratory center would lead to:

A. Tachypnea B. Hyperthermia
C. Respiratory alkalosis D. Lethargy

D. Matching Type

___1. Activated charcoal A. respiratory

___2. Potentially lethal B. end-organ injury
___3. Tachypnea C. acidemia
___4. Haemodialysis D. 1g/kg
___5. NaHCO3 E. >500 mg/kg