NSAID-Induced Gastropathy and GI Damage
The primary cause of gastric mucosal injury is the non-selective inhibition of the COX-1 enzyme. This leads to a marked drop in the synthesis of cytoprotective prostaglandins (PgE2, PgI2). Consequently, an imbalance between aggressive and protective factors develops: hydrochloric acid secretion increases, while mucus and bicarbonate production decreases.
Clinically, this manifests as mucosal ulceration and a high risk of upper gastrointestinal bleeding. For effective pharmacoprophylaxis, synthetic prostaglandin analogs (e.g., misoprostol) or proton pump inhibitors (e.g., omeprazole) are used. Switching to selective COX-2 inhibitors (e.g., celecoxib) also reduces risks. Enteric-coated formulations provide minimal clinical protection against gastropathy.
Effects on Hemostasis
Drugs in this group reliably inhibit platelet aggregation capability. In laboratory testing, this is reflected as an increased bleeding time.
It is essential to remember that the antiplatelet effect does not disappear immediately—it persists for several days after the complete cessation of the drug. This characteristic is critically important to consider when preparing patients for surgical procedures to avoid severe hemorrhagic complications.
Respiratory System and Aspirin-Exacerbated Respiratory Disease
Blockade of the cyclooxygenase pathway of arachidonic acid metabolism leads to the activation of an alternative cascade: the lipoxygenase pathway. This causes massive overproduction of leukotrienes, which provoke severe bronchospasm.
In addition, these agents affect acid-base balance:
- At therapeutic doses, they stimulate respiration by increasing alveolar ventilation.
- Toxic doses depress the respiratory center, leading to CO2 retention and the development of combined respiratory and metabolic acidosis.
Pediatric Considerations
The administration of salicylates (aspirin) to children during viral infections, such as influenza or varicella, is an absolute contraindication. This combination can precipitate Reye syndrome—an extremely dangerous, life-threatening condition.
This pathology is characterized by acute hepatic encephalopathy, rapid progression, and fatty infiltration of the liver and brain, featuring a high mortality rate. In pediatric practice, the only drugs of choice for managing fever are paracetamol (acetaminophen) and ibuprofen.
Pharmacokinetics and Dose-Dependency
These drugs are rapidly absorbed from the stomach and small intestine, reaching peak plasma concentration (Cmax) within 1–2 hours, and are capable of crossing the blood-brain barrier. The spectrum of action strictly depends on the daily dose:
- Low doses (80–325 mg/day) provide an antiplatelet effect.
- Medium doses (500–1500 mg/day) provide antipyretic and short-term analgesic action.
- High doses (greater than 3000 mg/day) are required to achieve an anti-inflammatory effect.
At therapeutic dosages, elimination follows linear kinetics with a half-life of approximately 3 hours. At high doses, enzymes become saturated, kinetics become non-linear, and the half-life can increase up to 15 hours.