Aspirin/Salicylic acid (Acidic in nature)

Indications :-

1. Acute coronary syndrome

2. Angina pectoris Prophylaxis 

3. Ischemic stroke Prophylaxis

4. Myocardial infarction Prophylaxis

5. Revascularization procedures Prophylaxis (PTCA ,CABG)

6. Ankylosing spondylitis

7. Rheumatoid arthritis

8. Osteoarthritis

9. Systemic Lupus Erythematosus

10. Colorectal carcinoma

Side effects :-

1) Gastrointestinal upset (Gastritis/GI bleeding) - Most common [ Decreased PGE2 formation due to Inhibition of COX1 activity in gastric mucosa leading to decreased mucus and bicarbonate secretion by epithelium . So gastric mucosa gets damaged by gastric acid]

2) Hypersensitivity to aspirin - [Note - Aspirin triad / Samter's triad - Aspirin intolerance , Bronchial asthma , Nasal polyps]

3) Reye syndrome / Acute Hepatic Encephalopathy - 

• Acute onset noninflammatory encephalopathy due to hyperammonemia (Rx- Osmotic diuretic , head elevation)

• Liver dysfunction due to Viral altered Salicylate induced mitochondrial injury which inhibits oxidative phosphorylation and fatty acid beta oxidation (Fatty liver / Hepatic steatosis on Liver biopsy) (Elevated AST , ALT)

• Hyperammonemia due to decreased activity of mitochondria (Rx- Phenylacetate-Sodium benzoate / Sodium polystyrene sulphate / Hemodialysis)

• Hypoglycemia (Rx- Dextrose containing fluids {D50 , D10 , D5} ; Target serum glucose 100-200mg/dl)

• Metabolic acidosis (Rx- Sodium bicarbonate)

• Coagulopathy [ Prolonged INR ]   (Rx- Cryoprecipitate , FFP/Fresh Frozen Plasma , Vitamin K)

• Coma

" A rare but fatal conditions in Patients less than 20yrs old that generally develop after treating viral infections (Influenza , Varicella , gastroenteritis infections) with aspirin or other salicylates" [Note - Paracetamol / Acetaminophen is considered Antipyretic of choice in children with viral infections to prevent Reye's syndrome] "

4) Aspirin toxicity :- 

leads to

•  HAGMA / High Anion Gap Metabolic Acidosis due to salicylic acid as well as Lactic acid accumulation (due to uncoupling of oxidative phosphorylation causing anerobic respiration)

•  Respiratory alkalosis  due to direct stimulation of respiratory centers

But acidemia worsens so

Rx - Airway management ; Alkalinsation of urine via bicarbonate drip to increase rate of excretion of aspirin  ; Activated charcoal +/- Bowel irrigation ; Hemodialysis

5) Affects kidney in dose-dependent manner 

(Low dose aspirin - Precipitate Hyperuricemia / Uric acid retention / Gout due to inhibition of Renal tubular secretion of uric acid ; 

High dose aspirin - Uricosuric effect / Uric acid excretion as Inhibition of Reabsorption of uric acid is more than Inhibition of Secretion of uric acid)

6) Intracerebral Hemorrhage 

Contraindications :-

1)Allergy to salicylates

2) Allergy to ibuprofen  (due to cross reactivity)

3) Asthma (Can precipitate bronchospasm ; so should be cautious)

4) Inborn coagulopathies (Hemophilia)

5) Childrens suffering viral illness

6) G6PD deficiency (as can precipitate  acute intravascular hemolytic anemia)

7) Peptic ulcer disease / Gastritis

8) Acquired diathesis (Yellow hemorrhagic fever , Dengue)

Pharmacokinetics :-

Aspirin follows saturation kinetics (at low plasma concentrations -First order kinetics/Constant fraction of drug is eliminated per unit time , Rate of elimination is proportional to plasma concentration ; at high concentrations - Zero order kinetics/Constant amount of drug is eliminated per unit time , Rate of elimination is independent of plasma concentration)

Mechanism of action :-

Irreversible cyclooxygenase 1 inhibitor by Acetylation (leading to inhibition of Synthesis of a Pro-aggregatory eicosanoid Thromboxane A2 in platelets leading to inhibition of Platelet aggregation - Reducing chances of clot formation / Antithrombotic effect at low doses <300mg/day)

Irreversible COX 1 and COX 2 inhibition (leading to inhibition of Prostacyclin (PGI 2) synthesis in Endothelial cells - Anti-inflammatory , Antipyretic and Analgesic effect)

Aspirin reaches adequate plasma levels by 20 minutes and exerts its platelet inhibitory effect by 60 minutes 

A single dose of aspirin inhibits platelet aggregation in 50% platelets for as late as 5 days after administration (Normal platelet life span is 7-10 days and only 10% platelets are replaced daily)

Note - Aspirin should be discontinued 7 days before surgery.

for thrombus formation only 20% platelets not acetylated by aspirin is sufficient

Doses :-

MI - 75 to 150 mg

ACS - 150 to 325 mg loading dose

Antithrombotic effect at low doses <300mg/day

Antipyretic and Analgesic effect at Intermediate doses 300-2400mg/day

Anti-Inflammatory effect at High doses 2400-4000mg/day

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