What is the use of Paracetamol (Acetaminophen)?

From the Guidelines

Paracetamol is recommended as a first-line agent for the treatment of musculoskeletal pain due to its efficacy and safety profile, with a recommended daily dose not exceeding 4000mg (4g) in 24 hours 1. The use of paracetamol in a multimodal regimen is a valid and effective option for postoperative pain management, as it has been shown to provide a cost-effective strategy to improve outcomes and patient satisfaction with a side-effect profile that is superior to opioids alone in moderate–severe acute postoperative pain 1. Some key points to consider when using paracetamol include:

• The standard adult dose is 500-1000mg every 4-6 hours, not exceeding 4000mg (4g) in 24 hours.
• For children, dosing is weight-based, typically 10-15mg per kilogram of body weight every 4-6 hours.
• Paracetamol works by inhibiting the production of prostaglandins in the central nervous system, which are chemicals that cause pain and fever.
• Unlike NSAIDs such as ibuprofen, paracetamol has minimal anti-inflammatory effects and doesn't irritate the stomach lining, making it suitable for people who cannot take NSAIDs.
• It's generally safe when taken as directed but can cause serious liver damage in overdose or when taken with alcohol, and the FDA recommends limiting daily acetaminophen intake to a maximum of 4 g 1. The combination of paracetamol with other medications, such as NSAIDs, can improve the quality of pain relief compared to the appointment of each of the drugs separately 1. However, caution is needed in the frail patient, especially in the context of coexisting liver disease, and the NCCN panel suggests that providers consider limiting chronic administration of acetaminophen to 3 g or less per day 1.

From the FDA Drug Label

Temporarily relieves minor aches and pains due to: headache muscular aches backache minor pain of arthritis the common cold toothache premenstrual and menstrual cramps Temporarily reduces fever The primary use of paracetamol is to provide temporary relief from minor aches and pains and to reduce fever. Key indications include:

• Headache
• Muscular aches
• Backache
• Minor pain of arthritis
• The common cold
• Toothache
• Premenstrual and menstrual cramps 2

From the Research

Paracetamol Overview

• Paracetamol is used worldwide for its analgesic and antipyretic actions, with a spectrum of action similar to that of NSAIDs and resembles particularly the COX-2 selective inhibitors 3.
• It is, on average, a weaker analgesic than NSAIDs or COX-2 selective inhibitors but is often preferred because of its better tolerance 3.

Mechanism of Action

• The mode of action of paracetamol has been uncertain, but it is now generally accepted that it inhibits COX-1 and COX-2 through metabolism by the peroxidase function of these isoenzymes 3.
• Paracetamol shows selectivity for inhibition of the synthesis of PGs and related factors when low levels of arachidonic acid and peroxides are available 3.
• It also inhibits other peroxidase enzymes, including myeloperoxidase, which may be associated with multiple inflammatory pathologies 3, 4.

Therapeutic Uses

• Paracetamol is effective in treating acute and chronic pain, and is active as a single agent and is additive or synergistic with NSAIDs and opioids 5.
• It is recommended as a first or second-line drug for acute pain and chronic pain, especially for patients with limited therapeutic options and for the elderly 5.
• Paracetamol is a viable alternative to NSAIDs, especially because of the low incidence of adverse effects, and should be the preferred choice in high-risk patients 6.

Dosage and Administration

• Dosage, therapeutic intervals, and toxic potential are different for children and adults, and guidelines for treating children with paracetamol should be followed 7.
• A dose reduction is recommended in patients with liver disease or malnourished, and genotyping may improve efficacy and safety 5.
• Fast dissolving formulations of paracetamol provide superior and more extended pain relief that is similar to intravenous paracetamol 5.

Safety and Efficacy

• There is considerable debate about the hepatotoxicity of therapeutic doses of paracetamol, and much of the toxicity may result from overuse of combinations of paracetamol with opioids 3.
• Paracetamol has a favorable safety and tolerability record, but recent reports have questioned its therapeutic value and safety 5.
• The addition of an NSAID to paracetamol may confer additional analgesic efficacy compared with paracetamol alone, but future studies are required to assess the potential increase in side-effects from their combined use 6.