From the Guidelines
Tylenol (acetaminophen) works primarily by inhibiting cyclooxygenase (COX) enzymes in the central nervous system, which reduces the production of prostaglandins that mediate pain and fever. The mechanism of action of Tylenol is not fully understood, but it is known to have minimal peripheral anti-inflammatory effects and does not significantly inhibit COX enzymes in peripheral tissues, which explains why it relieves pain and reduces fever but lacks substantial anti-inflammatory properties 1. This central action makes Tylenol effective for pain relief and fever reduction while causing fewer gastrointestinal side effects compared to NSAIDs. Some evidence suggests that the mechanism of action of Tylenol may also involve serotonergic pathways and the endocannabinoid system, although more research is needed to fully understand its effects 1. It is worth noting that the use of Tylenol has been associated with risks of severe liver injury, and the FDA has recommended limiting the amount of acetaminophen in prescription products to 325 mg per tablet, capsule, or other dosage unit to reduce this risk 1. Overall, the mechanism of action of Tylenol is complex and not fully understood, but its central action and lack of peripheral anti-inflammatory effects make it a useful medication for pain relief and fever reduction. Key points about the mechanism of action of Tylenol include:
- Inhibition of COX enzymes in the central nervous system
- Minimal peripheral anti-inflammatory effects
- Lack of significant inhibition of COX enzymes in peripheral tissues
- Possible involvement of serotonergic pathways and the endocannabinoid system
- Association with risks of severe liver injury, particularly at high doses 1.
From the Research
Mechanism of Action of Tylenol (Acetaminophen)
The mechanism of action of Tylenol (acetaminophen) is complex and not fully understood. However, several studies have proposed different mechanisms:
- Inhibition of cyclooxygenase (COX) enzymes: Acetaminophen has been shown to inhibit COX-1 and COX-2 enzymes, although it is a weak inhibitor in vitro 2, 3.
- Inhibition of prostaglandin synthesis: Acetaminophen has been shown to reduce levels of prostaglandin metabolites in urine, but does not reduce synthesis of prostaglandins by blood platelets or by the stomach mucosa 2.
- Activation of descending serotonergic pathways: Acetaminophen has been shown to have a central analgesic effect that is mediated through activation of descending serotonergic pathways 4.
- Action through an active metabolite: Acetaminophen is metabolized to N-acylphenolamine (AM404), which acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 receptors in the brain 5, 6, 4.
- Inhibition of myeloperoxidase: Acetaminophen has been shown to inhibit myeloperoxidase, which may be associated with multiple inflammatory pathologies 3.
Key Findings
- Acetaminophen has a spectrum of action similar to that of NSAIDs, but with weaker analgesic and anti-inflammatory effects 3.
- Acetaminophen has a better tolerance profile than NSAIDs, with less gastrointestinal toxicity 3.
- The analgesic effects of acetaminophen are reduced by inhibitors of many endogenous neurotransmitter systems, including serotonergic, opioid, and cannabinoid systems 3.
- There is debate about the hepatotoxicity of therapeutic doses of acetaminophen, with some studies suggesting that much of the toxicity may result from overuse of combinations of acetaminophen with opioids 3.