Acetaminophen Poisoning - Essay Example

1. Innate immune response mechanism: Cell damage and stress in the liver due to the reaction of active metabolites can lead to activation of cells of the innate immune system, including Kupffer cells, natural killer cells, and NKT cells. These cells produce proinflammatory mediators such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β which worsen the liver cell injury. Though the innate immune cells produce IL-10, IL-6, and certain prostaglandins, which are actually hepatoprotective, the imbalance of hepatotoxic and hepatoprotective mediators is probably what causes the damage.

These cells also secrete chemokines to further recruit inflammatory cells. This mechanism occurs in drugs like acetaminophen (Holt, 2006). 2. Adaptive immune response mechanism: Some drugs like diclofenac and halothane interact with immune receptors causing the release of drug-specific antibodies and T-cells which cause cell damage and death. The main mechanism of toxicity due to acetaminophen is through its metabolite NAPQI. This is normally conjugated by glutathione (and excreted through kidneys) which gets depleted in high doses.

N-Acetylcysteine (NAC) is the drug of choice for the treatment of an acetaminophen overdose. It provides cysteine for glutathione synthesis and increases glutathione availability to bind to NAPQI. It also forms an adduct directly with the toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine (sulfate conjugation). Other than these effects, it functions as an anti-inflammatory and antioxidant. It increases local nitric oxide concentrations which cause vasodilatation leading to increasing in microcirculatory blood flow and local oxygen delivery to peripheral tissues.

By this, the deleterious effects of NAPQI are minimized (Farrel, 2006).