Salicylate toxicity

a detailed presentation on salicylates toxicity:
1. definition
2. Physical Appearance
3. introduction
4. examples
5. therapeutic uses
6. pharmacokinetics
7. toxicokinetic
8. toxic dose
9. mechanism
10. interactions
11. toxic features
12. diagnosis
13. management
14. treatment
15. autopsy features

1. Presentation on Salicylates toxicity Balaji MN pharm-D Sarada vilas college of pharmacy, Mysuru

2. Salicylates: Definition: Salicylates are derivatives of salicylic acid and include acetyl salicylic acid, sodium salicylate, and methyl salicylate. Salicin , is a naturally occurring salicylate obtained from several plants. Physical Appearance: Acetyl salicylic acid is an odourless , white, crystalline powder with an unpleasant saline taste. Sodium salicylate occurs as odourless , white scaly crystals with the same unpleasant saline taste. Methyl salicylate is a colourless liquid with aromatic odour and sweetish taste.

3. Introduction: Hoffman , a chemist first synthesized acetyl salicylic acid in the laboratory in 1897, with the help of his chief pharmacologist Heinrich Dreser . The name “aspirin” was coined in 1899. Usually salicylate toxicity occurs predominantly in adolescents and young adults. Overdoses in children are commonly accidental where as in elderly adults occurs as therapeutic disasters. The severity aspirin overdose are often neglected by ER personnel.

4. Examples of salicylates: Aloxiprin , Aluminium aspirin, Ammonium salicylate, Antipyrine salicylate, Aspirin, Benorylate , Bismuth subsalicylate, Bromosalicylic acid acetate, Calcium aminosalicylate , Calcium carbaspirin , Carbamoylphenoxyacetic acid, Choline salicylate, Diethylamine salicylate, Ethyl salicylate, Fendosal , Glycol salicylate, Homomenthyl salicylate, Lithium salicylate, Magnesium salicylate, Menthyl salicylate, Phenazone salicylate, Phenyl aminosalicylate , Phenyl salicylate, Physostigmine salicylate, Potassium aminosalicylate , Potassium salicylate, Salicylamide , Salicylic acid, Salsalate , Silver salicylate, Sodium aminosalicylate , Sodium salicylate, Sodium thiosalicylate , Trolamine salicylate.

5. Therapeutic uses: Analgesic. Anti-inflammatory. Antipyretic. Keratolytics. Antiplatelates. Rheumatoid arthritis.

6. Pharmacokinetics: Absorbed rapidly by passive diffusion in stomach and intestine. 90% of drug binds to albumin. pKa value of 3.5 Metabolized in liver. Excreted through urine. Peak serum levels at 30mins.

7. Toxicokinetics : Above 30 mg/ml. Delayed absorption due to pylorospasm , bezoar formation. Peak serum levels aren’t achieved in 4-6 or more hours. At toxic levels, elimination routes are saturated. T oxic dose: A spirin : A cute: >150 mg/kg M oderate : 300 mg/kg S evere : 300-500 mg/kg L ethal : >500mg/kg.

8. Mechanism: 1. Salicylates Stimulate T he respiratory centre in the brainstem hyperventilation and respiratory alkalosis 2. It also interferes with Krebs cycle inhibiting ATP production, and ses lactate production. leads ketosis and a wide anion-gap metabolic acidosis. 3 . Salicylates are extremely irritating to the GI mucosa, and overdose often results in hemorrhagic gastritis.

9. Interactions: Salicylates with acetazolamide , which causes confusion, fatigue, hyperchloraemic metabolic acidosis, incontinence, lethargy and etc. Salicylates with alcohol can cause stomach bleeding.

10. Toxic features: Acute poisoning: Early - Nausea, vomiting, sweating, tinnitus, hyperventilation. Late - Deafness, hyperactivity, agitation, delirium, can even lead to coma. Complications - Metabolic acidosis, pulmonary oedema , rhabdomyolysis, cardiac depression, thrombocytopenia, Gastrointestinal bleeding and have a severe risk of Reye’s syndrome. Chronic poisoning: it is characterized by slow onset of confusion, disorientation, coma and hallucination. pseudosepsis syndrome characterized by fever, leukocytosis, hypotension, and multi-organ system failure. Prolonged PT .

11. Diagnosis: By monitoring the serum levels Blood report like CBC, PT time. Laboratory findings- -Anion-gap acidosis. - Hypokalaemia . - Hypocalcaemia . - Hypoglycaemia . Bed-side tests- 1. Ferric chloride test: few drops of 10% ferric chloride + 1ml urine. purple color Presence of salicylates. 2. Trin der’s test: 0.1ml of trinder’s reagent + 2ml sample( urine, stomach contents, ) Mix for 5 secs strong violet color Presence of salicylates.

12. Management: Decontamination. Blood monitoring like- ABG - ASA level – mg/ dL - Electrolytes – k+, BUN/Cr Fluid resuscitation Electrolyte repletion. In severe cases, parenteral opioids, corticosteroids, IV fluids are given. The patients are being treated symptomatically ( for major symptoms ).

13. Treatment: Stomach wash can be used up to 12hrs of ingestion. Activated charcoal- each gram of AC (activated charcoal ) can absorb 550mg of the drug. Urinary alkalinisation, which is usually confused with forced diuresis. Mild poisoning: 1mEq/kg of NaHCO3 in 5% dextrose, until alkalinisation is achieved. Severe poisoning: additional bolus therapy of 50-100 mEq of NaHCO3 over 2-3hrs. Till the serum salicylate level (35 mg/100 ml ) and urinary pH (7.5-8 ) is achieved. Hemodialysis. Supportive therapy. Reye’s syndrome: Admit to ICU. Rest the head at 40˚ Mannitol IV ( 0.2-1.0 gm/kg ) Acute hyper ventilation. -Short acting barbiturates.

14. Autopsy features: Petechiae (minor bleeding which appears purple color ) on skin. Erosion of gastric mucosa. Pulmonary and cerebral oedema .

15. Thank you…