Acetaminophen

Primary tabs

DRUGS
Acetaminophen

Acetaminophen is a centrally acting analgesic and anti-pyretic. It is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fever. Acetaminophen is effective in the central nervous system and acts primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin synthesis.

Introduction

Acetaminophen is a centrally acting analgesic and anti-pyretic. It is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fever. Acetaminophen is effective in the central nervous system and acts primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin synthesis.

Indications

  • Pain (due to arthritis, backache, common cold, muscular ache, toothache, headache, premenstural and menstrual cramps)
  • Fever

Pharamcological Action

Acetaminophen acts primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centers of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.

Dosage

For adults and children 12 years of age and older: 650 to 1000 mg every 4 to 6 hours

For children under 12 years of age: 10 to 15 mg/kg every 4 to 6 hours

Pharmacokinetics

Acetaminophen is rapidly and almost completely absorbed. It primarily undergoes glucuronidation (45-55% of the dose) in which this process is facilitated by UGT1A1, UGT1A6, UGT1A9, UGT2B15 in the liver or UGT1A10 in the gut. 30-35% of the dose undergoes sulfation. This biotransformation is facilitated by SULT1A1, SULT1A3, SULT1A4, SULT1E1 and SULT2A1. A small percentage of acetaminophen is oxidized by CYP2E1 to form N-acetyl-p-benzo-quinone imine (NAPQI), a toxic metabolite which is then conjugated to glutathione and excreted renally. Approximately 80% of acetaminophen is excreted in the urine after conjugation and about 3% is excreted unchanged.

Contraindications

  • In patients with known allergy to acetaminophen.
  • In patients that are suffering from various liver problems or acute liver failure.
  • Patients suffering from serious kidney problems should avoid its use.
  • In patients experiencing shock and overdose of acetaminophen.
  • Contradicted in patients on poor nutrition.

Drug Interactions

  • Concomitant use of acetaminophen and alcohol affect the liver.
  • Acetaminophen when administered together with leflunomide may cause serious liver disorders.
  • Prilocaine when taken with acetaminophen can cause methemoglobinemia that reduces the oxygen-carrying capacity of the blood to different organs.
  • Lomitapide use along with acetaminophen may increase the risk of liver disorder.
  • Teriflunomid when given with acetaminophen increases the risk of liver problems.

Side effects

Common (affecting between 1 in10 to 1 in 100)

  • Fever with or without chills
  • Nausea
  • Itching
  • Rash
  • Headache

Uncommon (affecting 1 in 100 to 1 in 1000)

  • Bloody, tarry stools
  • Cloudy urine
  • Pain in the lower back and/or side
  • Pinpoint red spots on the skin
  • Sore throat
  • Canker sores
  • Decreased urine output

Very rare (affecting less than 1 in 10,000)

  • Unusual bleeding or bruising
  • Unusual tiredness
  • Jaundice

Precautions

  • Avoid in patients who are allergic to acetaminophen.
  • Avoid intake of acetaminophen in patients having pre-existing liver disease.
  • Patients making regular use of alcohol or alcohol abuse should also avoid intake of acetaminophen.
  • Avoid in pregnant women or women having breastfeed.

Clinic Evidence

  • Seventeen blinded, randomized controlled trials with children (<18 years) receiving either ibuprofen or acetaminophen to treat fever or moderate to severe pain were considered. Ibuprofen (4-10 mg/kg) and acetaminophen (7-15 mg/kg) showed comparable efficacy (3 pain relief trials; 186 children). The risk ratio point estimates were 1.14 (95%confidence interval [CI], 0.82-1.58) at 2 hours after receiving the dose, and 1.11 (95% CI, 0.89-1.38) at 4 hours. Acetaminophen reduced the temperature (10-15 mg/kg) at 2, 4, and 6 hours after treatment. Single doses of ibuprofen (4-10 mg/kg) and acetaminophen (7-15 mg/kg) have similar efficacy for relieving moderate to severe pain and fever. Acetaminophen was effective at (10-15 mg/kg) at 2, 4, and 6 hours post-treatment.

References

Log in or register to post comments