Paracetamol | Pharmacology Mentor

Generic Name

Paracetamol

Mechanism

Paracetamol (acetaminophen) exerts its antipyretic and analgesic effects largely by
• Inhibiting central cyclooxygenase‑2 (COX‑2) activity, thereby reducing prostaglandin synthesis in the hypothalamus and spinal cord.
• Modulating the serotonergic descending pain pathway (5‑HT₁A receptors).
• Blocking voltage‑gated calcium channels in central nociceptive pathways.
• Limited peripheral COX inhibition explains its minimal anti‑inflammatory action.

> *Key point:* Despite being an NSAID‑like structure, it lacks significant peripheral COX inhibition, contributing to its safety profile in most patients.

Pharmacokinetics

Absorption: Rapid and almost complete after oral dosing; peak plasma levels in 30–60 min.
Distribution: Widely distributed; CNS penetration is high; albumin binding ≈ 15 %.
Metabolism: Predominantly glucuronidation and sulfation in the liver; a small fraction (≈ 5–10 %) oxidized by cytochrome P450 3A4/2E1 to the hepatotoxic N‑acetyl‑p‑benzoquinone imine.
Elimination: Mainly via urinary conjugates (glucuronide, sulfate); renal clearance ≈ 80 % of the dose.
Half‑life: 2–3 h in healthy adults; longer in hepatic impairment.
Special populations: No dose adjustment required for renal impairment; cautious use in severe hepatic disease.

Indications

Analgesia: Mild‑to‑moderate pain (post‑operative, dental, musculoskeletal, headache, osteoarthritis).
Antipyretia: Fever reduction in infectious, inflammatory, or postoperative states.
Adjunct therapy: Combination with opioids or NSAIDs for multimodal pain control.
Pregnancy & lactation: Preferred analgesic/antipyretic (category B).

Contraindications

Known hypersensitivity to acetaminophen or any formulation excipients.
Severe hepatic impairment (Child‑Pugh C); avoid use altogether.
Regular high‑dose (> 4 g/day) intake for ≥ 14 days; risk of hepatotoxicity.
Alcohol abuse or chronic liver disease: increase monitoring or avoid.
Concurrent use of *glycol ethers* can potentiate hepatocellular injury.

Dosing

Population	Dose	Frequency	Duration
Adults, weighing 70 kg	500–1000 mg PO	Every 4–6 h, max 4 g/day	24 h or as needed
Elderly or hepatic impairment	500–700 mg PO	Every 6–8 h, max 3 g/day	24 h or as needed
Children (≥ 2 y)	10–15 mg/kg PO	Every 4–6 h, max 60 mg/kg/24 h	24 h or as needed

| Pediatrics *Tip:* Use weight‑based dosing in pediatrics to avoid accumulation.

Adverse Effects

Common (≤ 5 %): Nausea, rash, GI discomfort.
Serious (> 5 % in special circumstances):
Hepatotoxicity: LFT elevation → fulminant hepatic failure in overdose.
Hypersensitivity reactions (angioedema, anaphylaxis).
Rare hematologic: thrombocytopenia, agranulocytosis.
Contact dermatitis from excipients.

> Overdose warning: > 7.5 g in 24 h (VH 8 g) → immediate activated charcoal ± N‑acetylcysteine.

> Drug interactions: Lower toxicity of carbamazepine; increased risk with valproic acid due to hepatic metabolism.

Monitoring

Baseline & periodic LFTs in patients on > 2 g/day, chronic use, or hepatic disease.
Renal function: Monitor if concomitant nephrotoxic agents (NSAIDs, aminoglycosides).
Blood counts: If patient presents with unexplained cytopenias.
Blood pressure: Rare risk of hypertension when combined with other substances.
In pregnancy: Monitor for cholestasis symptoms; avoidance of high dose.

Clinical Pearls

“Acetaminophen” vs. “Paracetamol”: Same compound; label as Paracetamol/Acetaminophen for clarifying international names in charts.
Safe in pregnancy: FDA Category B; avoids the teratogenic risks of many NSAIDs.
No dose modification for renal failure: However cautious use with other hepatotoxic meds.
Watch the peak plasma concentration with IV infusion: Over‑rapid dosing can precipitate liver enzyme elevation.
Self‑medication: Educate patients to avoid combining multiple OTC products containing acetaminophen (e.g., cold/flu combos).
Chronic pain protocols: Use the lowest effective dose for the shortest duration; combine with NSAIDs or gabapentinoids to reduce total acetaminophen exposure.
In pediatric dosing: Check the weight‑based calculation to prevent accidental overdose in children.
Flammability of IV bag: Keep away from open flame or heat source; whereas oral formulations are safe.

--
• *This drug card is intended as a quick‑reference guide for medical students and clinicians. For complex cases or therapeutic drug monitoring, consult current guidelines and the product monograph.*