ASPIRIN TOXICITY

PRACTICAL TOXICOLOGY
TIKRIT UNIVERSITY
COLLAGHE OF PHARMACY
2022/2023
PREPERED
BY
Ph.Nagham Qassiem Ahmed
INTRODUCTION
●Aspirin is one of NSAIDs widely used in clinical medicine as
analgesics, antipyretics, anti inflammatory, antiplatelet and
antirheumatics.
●Aspirin is one of the oldest medications that remains a part of
current Practice Intentional salicylate overdose usually occurs
predominantly in adolescents & young adults.
●Overdoses in children are usually accidental & in the elderly they
occur as therapeutic misadventures

●This is an important problem because delay in treatment of

severe intoxication is associated increased mortality in severe
cases.
■ Aspirin should not be prescribed to children aged <16years unless
there are compleling clinical indication
■
■ The particular concerns about Rye’s syndrome usually seen to be
related to higher doses of aspirin >40mg/kg

■ ●When combined with the fact that aspirin is readily avaliable , Aspirin
toxicity remaines an important clinical problem
■ With good management mortality rates are low but even at best about
5% of severely toxic patients die, usually from cardiovascular & central
nervous system complications.
Pharmacokinetics
Absorption:
Rapidly absorbed by passive diffusion in the stomach After
absorption ASA is de-acetylated

Distribution:
●%90bound to albumin in the blood at a dose of 10 mg/dl.
●An acidic pH promotes the movement of salicylate into the tissues
●Has a very short half-life (30 min).
Reach peak levels in 60- 15minutes

Elimination:
%90metabolized in the liver, 10% unchanged
Excreted in the urine (PH dependent)
Clinical presentation
Asymptomatic:blood conc. 45 mg/dl

❖Mild toxicity: Nausea, Gastritis, Mild hyperpnea, Tinnitus. Occur at

dose 150 mg/kg

❖Moderate toxicity: Hyperpnea, Hyperthermia, Sweating, Dehydration,

Marked lethargy, Possible excitement. Occur at dose 300- 150mg/kg

❖Severe toxicity: Severe hyperpnea, Coma, Convulsions, Cyanosis,

Pulmonary edema, Respiratory failure, Cardiovascular collapse. Occur
at dose 500 – 300 mg/kg.

❖Lethal: coma, death. Occur at dose 500 ‘ mg/kg.

Mechanism of action
1_ Salicylates directly stimulate the respiratory center in the medulla resulting in
hyperventilation

CO2H + 2 OH2CO3H+HCO 3

)respiratory alkalosis)

_2_Uncoupling of oxidative phosphorylation ....The cell becomes dependent upon

anaerobic metabolism, resulting in accumulation of lactate

3_Compensated _ by renal excretion of bicarbonate

)compensated metabolic acidosis(

TOXIC DOSE
●Toxic dose = 150 mg/kg
●Minimal lethal dose = 450 mg/kg
●Assessing Salicylate Poisoning Dose

●Less than 150 mg/kg of aspirin- no symptoms to mild

toxicity
●Ingestions of 300-150mg/kg –mild to moderate toxicity
●Ingestions of 500-300mg/kg –Serious toxicity
●Greater than 500mg/kg –potentially lethal
Laboratory analysis
_1Electrolytes, BUN, creatinine, glucose, serum osmolarity,
calcium, arterial blood gases, PT and partial thromboplastin
(PTT) time, Creatinine phosphokinase may be included to
assess the presence of rhabdomylosis.

2_Urine should be tested for pH, presence of ketones and

hemoglobin.

3_An ECG should be obtained for all patients as a screening

test for potentially life-threating electrolyte abnormalities
secondary to dehydration, hypokalemia, hyperkalemia or
hypercalcemia.
Laboratory analysis
■ _4 _Salicylate Levels

■ A-A rapid qualitative test for presence of salicylates may be

done by adding several drops of 10% ferric chloride to 1
ml of boiled urine. A purple color change indicate the
presence of salicylates.
■
■ B-Serum measurement of salicylates are important after
acute single ingestion. Initial levels on presentation and at
6 hr .After ingestion may be obtain and plotted on the
done nomogram.
MANAGEMENT
EMERGENCY AND SUPPORTIVE MEASURES:

Maintain airway and assist ventilation if necessary. Administer

supplemental oxygen and establish intravenous access.

Fluid resuscitation :

●Correction of dehydration with 0.9% sodium chloride or lactated

Ringer solution

●10to 20 mL/kg/h over 1 to 2 hours until a good urine flow is

established of at least 2 to 3 mL/kg/h
GI decontamination :

Gastric lavage in the first hr (warmed NS 38C,protect

●

airway)

●Activated charcoal in the first 4 hr, 2-1g/kg

(maximum 100g)

●Whole-bowel irrigation (WBI) with polyethylene

glycol(enteric coated or slow release formulas, 2 L/h
(20 mL/kg/h until the rectal effluent is clear(
Enhanced elimination:
Urinary alkalinization with sodium bicarbonate: 1 to
2 mEq/kg of sodium bicarbonate IV bolus, then
infusion of DW5% with 100 to 150 mEq of sodium
bicarbonate and 20 to 40 mEq of potassium chloride
in each liter at a rate of 1.5 to 2.5 mL/kg/h

Hemodialysis :

Management of patients with salicylate poisoning and a

serum salicylate level >100 mg/dL after acute ingestion or
>40 mg/dL after chronic ingestion, altered mental status,
renal failure, pulmonary edema, progressive clinical
deterioration, refractory acidosis, or failure to respond to
more conservative therapy.
■ Glucose should be administered to treat CNS
Hypoglycemia and ketosis

■ Coagulation defects may treated with Vitamin

K S.C every day

■ Seizure treated with diazepam