Essay questions

MOA of acetaminophen and the antidote N-acetylcysteine

Acetaminophen can majorly be metabolized by phase II enzymes such as sulfotransferase into sulfate and UDP glucuronyl transferase to glucuronide. The remaining is converted into a reactive metabolite known as NAPQI by cytochrome P450 2E1. This intermediate can cause liver tissue damage. Under normal levels of acetaminophen, there is sufficient glutathione to bind to NAPQI and remove it. However when there is an overdose, glutathione becomes depleted allowing for and accumulation of the toxic intermediate NAPQI.

N-acetylcysteine replenishes glutathione that detoxifies NAPQI.

MOA of salicylate

Salicylate intoxication causes hyperventilation which causes reduced PCO2 levels that leads to respiratory alkalosis. Body switches to glycolysis leading to lactic acid buildup causing metabolic acidosis.

MOA of methanol and the antidote fomepizole

Formic acid is formed causing metabolic acidosis.

Fomepizole inhibits alcohol dehydrogenase.

MOA of ethylene glycol and the antidote fomepizole

Lactic acid formation causing acidosis and formation of oxalate crystals leading to renal damage

Fomepizole inhibits alcohol dehydrogenase.

MOA of calcium channel blockers and the antidote glucagon

Prevent the influx of calcium through the slow calcium channels in cardiac and vascular smooth muscle.

Mechanism of Action (Overdose) prolongs the refractory period of cardiac muscle and depresses impulse conduction through the SA node (ie slows the heart rate).

Glucagon increases intracellular Ca2+ by: Stimulates adenylate cyclase (AC) which increases cyclic adenosine monophosphate (cAMP). This results in recruitment of Ca2+ channels.