Paracetamol (Acetaminophen)Lecture Notes

Flashcards covering the history, mechanism of action, metabolism, toxicity, and clinical treatment parameters of paracetamol (acetaminophen).

Paracetamol (acetaminophen)

A synthetic non-opioid analgesic and antipyretic discovered in Germany at the end of the 19th century.

Cyclo-oxygenase (COX-2 & COX-3)

Enzymes in the central nervous system inhibited by paracetamol; they are involved in prostaglandin synthesis and nerve transmission for pain and fever.

Peroxidase regeneration

An oxidation process paracetamol inhibits to prevent inactive COX from becoming active, especially when peroxidase levels are low in central nervous system cells.

Serotoninergic inhibitory pain pathways

Descending pathways activated by paracetamol which indirectly reduce pain perception by acting on the neurotransmitter serotonin.

Glucuronidation

The most common Phase II conjugation reaction, metabolizing $45-55\%$ of paracetamol using the enzyme uridine diphosphate (UDP)-glucuronyl transferase.

Sulphate Conjugation

A Phase II reaction catalyzed by sulphotransferases in the liver, kidney, and intestine, accounting for $30-35\%$ of paracetamol metabolism.

NAPQI (N-acetyl-p-benzoquinoneimine)

A toxic, minor alkylating metabolite formed by the hepatic cytochrome P450 isoenzyme system ($CYP2E1$ and $CYP3A4$).

Glutathione (GSH)

A tripeptide comprised of glutamic acid, glycine, and cysteine that irreversibly conjugates with NAPQI to form non-toxic excretable derivatives.

Encephalopathy

Brain malfunction caused by the build-up of toxins, occurring as hepatic necrosis develops following a paracetamol overdose.

Oliguria

A symptom of renal failure following paracetamol overdose characterized by low urine output.

Rumack-Matthew Nomogram

A tool used to assess the risk of liver damage based on a line between $200\,mg/L$ at 4 hours and $30\,mg/L$ at 15 hours post-ingestion.

N-acetylcysteine (NAC)

An intravenous treatment used to replenish cellular glutathione stores for NAPQI conjugation and to repair oxidative damage.

Kings College Criteria

A set of clinical indicators for immediate liver transplant referral, including arterial $pH < 7.3$, $INR > 6.5$, and creatinine $> 300\,\mu mol/L$.

CYP2D6 gene duplication

A genetic factor leading to ultra-rapid metabolism, which increases susceptibility to paracetamol toxicity.

Lactic acidosis

A condition involving the build-up of lactate in the blood, serving as a poor prognostic factor if systemic acidosis is evident after 24 hours.