Analgesic · Antipyretic
Acetaminophen (Tylenol)
Also called Tylenol, paracetamol
Indications
- Mild to moderate pain, and moderate to severe pain with opioids (multimodal, opioid-sparing)
- Fever
- Opioid adjunct for ICU pain (PADIS 2018)
- Shivering control in temperature management (off-label)
On the quick cards
Mechanism of action
Acetaminophen acts mainly in the CNS. It inhibits COX-1 and COX-2 at the peroxidase site, which works only where peroxide is low, as in the brain; high peroxide at inflamed tissue overrides it, so it is barely anti-inflammatory or antiplatelet. Its deacetylated metabolite p-aminophenol is converted in the brain by fatty acid amide hydrolase to AM404, which acts on TRPV1 and CB1 receptors; descending serotonergic pathways also contribute. Lower hypothalamic PGE₂ resets the temperature set point.
Pharmacology
- CNS: analgesia and antipyresis without sedation or respiratory depression
- Hematologic: no effect on platelets or hemostasis at therapeutic doses (label)
- GI and Renal: no gastric injury and little renal prostaglandin effect, unlike NSAIDs
- Cardiovascular: IV doses lowered BP by 15% or more in about half of critically ill patients (Cantais 2016)
- Metabolic: lowers fever, but did not change ICU-free days in ICU infection (HEAT 2015)
Pharmacokinetics
| Onset | IV analgesia in 5–10 min; fever falls within 30 min |
|---|---|
| Peak | Plasma peak at the end of the 15-min IV infusion, up to 70% above oral (label); analgesia at about 1 h |
| Duration | 4–6 h |
| Half-life | About 2.4 h (label); longer in liver failure and overdose |
| Distribution | Vd about 0.8–1 L/kg, not into fat; crosses the BBB and placenta |
| Protein binding | 10–25% (label) |
| Metabolism | Liver: glucuronidation 40–67%, sulfation 20–46%, about 5% oxidized by CYP2E1 (also 1A2, 3A4) to NAPQI, which glutathione detoxifies |
| Elimination | Over 90% in urine within 24 h, under 5% unchanged (label) |
| Bioavailability | Oral about 88%; rectal erratic |
| Organ failure | CrCl 30 mL/min or less: longer intervals, lower daily dose (label); dialyzable |
Chemistry
- N-(4-hydroxyphenyl)acetamide (paracetamol), a para-aminophenol derivative and the active metabolite of phenacetin; not an NSAID
- Achiral; phenol pKa about 9.4, so un-ionized at pH 7.4; small and moderately lipophilic (log P 0.5)
- IV 10 mg/mL with mannitol and cysteine, pH about 5.5, about 290 mOsm/kg; use within 6 h of opening; do not refrigerate (label)
- NAPQI (N-acetyl-p-benzoquinone imine) binds liver cell proteins once glutathione is depleted
Adverse effects and cautions
In the one-pagers
- Medical Emergencies: Neuro, Endocrine, Blood and InfectionThyroid, sickle cell, hemophilia: Thyroid storm: Off antithyroid drug, infection; 38 °C+, HR 130+ or fast AF, delirium: Cool, fluid, acetaminophen, no aspirin; ask medical direction before rate control: ED, early notice
- Toxidromes and AntidotesThe first hour: approach to the poisoned patient: Every intentional overdose: acetaminophen (silent early) and salicylate levels, electrolytes with anion gap, measured osmolality, ethanol, venous gas with lactate, CK, ECG and a pregnancy test.
- ABG Interpretation in 6 StepsCauses in depth: High-gap acidosis: MUDPILES is the classic list (methanol, uremia, DKA, propylene glycol, isoniazid and iron, lactate, ethylene glycol, salicylates). GOLDMARK (Mehta 2008) fits the ICU better: glycols, 5-oxoproline (regular acetaminophen in malnourished or septic patients), L-lactate, D-lactate (short bowel), methanol, aspirin, renal failure and ketoacidosis (diabetic, alcoholic,
- ACLS Algorithms in BriefPost-arrest care: targets, temperature and prognosis: Shivering: score it (Bedside Shivering Assessment Scale) and step up from acetaminophen, buspirone, magnesium and skin counterwarming to sedation and opioid, paralysis last.
- BurnsWound care, pain and daily nursing checks: Burn pain is background, breakthrough and procedural, and dressing changes hurt most. Give opioids IV during resuscitation, since subcutaneous and IM absorption is unreliable, and expect doses to climb with tolerance. Add scheduled acetaminophen, ketamine for procedures, gabapentinoids for neuropathic pain and itch, and distraction such as virtual reality
- Hypothermia, Heat Stroke and DrowningCooling: methods, speed, stopping and drugs: Antipyretics lower a raised hypothalamic set point, which heat stroke does not have, and aspirin and acetaminophen can worsen its coagulopathy and liver injury (Bouchama 2007); SCCM 2025 advises against routine antipyretics and limits prophylactic antibiotics and antiseizure drugs to research. Dantrolene did not shorten cooling (67.9 vs 69 min) in a 52-
Practice Medical Emergencies: Neuro, Endocrine, Blood and Infection questions free49 exam-style questions with rationales on the topic where Acetaminophen comes up most. No account or download needed.
In the algorithms
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Sources
- FDA label: Ofirmev (2018)
- FDA label: Acetaminophen Injection, Baxter (2024)
- Ohashi 2020 (mechanism)
- Cantais 2016 (IV hypotension)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.