Pharmacology of paracetamol

Pharmacology of paracetamol 

 Paracetamol, also known as acetaminophen, is a common pain reliever and fever reducer used worldwide. It is available over the counter and is a part of many prescription medications. This article provides an overview of the pharmacokinetics and pharmacodynamics of paracetamol, including its absorption, distribution, metabolism, excretion, mechanism of action, dosage, adverse effects, contraindications, and interactions.

1. Pharmacokinetics

a. Absorption mechanism

Paracetamol is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are reached within 30-60 minutes of ingestion. The drug is also available in other forms such as suppositories, intravenous injections, and syrup.

b. Distribution in body

Paracetamol is distributed throughout the body after absorption. The drug is distributed into most body tissues, with the highest concentrations found in the liver, kidney, and brain. Paracetamol does not accumulate in body tissues, and the concentration of the drug in the body decreases as it is metabolized and excreted.

c. Metabolism mechanism

Paracetamol is primarily metabolized in the liver. The major metabolic pathway is glucuronidation and sulfation, which leads to the formation of inactive metabolites that are excreted in the urine. A small fraction of paracetamol is metabolized via the cytochrome P450 system, primarily CYP2E1, to form a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which can cause liver damage if it accumulates in high concentrations.

d. Excretion mechanism

Paracetamol and its metabolites are eliminated mainly by the kidney. The half-life of paracetamol is about 2-3 hours in adults, but may be longer in neonates and in patients with liver or kidney disease. The drug is excreted primarily in the urine as glucuronide and sulfate conjugates, and a small amount is excreted unchanged.

2. Pharmacodynamics 

a. Mechanism of action

Paracetamol's mechanism of action is not fully understood, but it is believed to involve inhibition of cyclooxygenase (COX) enzymes, particularly COX-2, which reduces the production of prostaglandins, substances that cause pain and fever.

b. Dose required

The recommended dose of paracetamol for adults is 325-1000 mg every 4-6 hours, not to exceed 4 grams per day. The recommended dose for children is based on their weight, with a maximum dose of 15 mg/kg every 4-6 hours.

c. Adverse effects

The most common adverse effects of paracetamol are nausea, vomiting, and abdominal pain. These side effects are generally mild and transient. Rare but serious adverse effects include liver damage, particularly in overdose or in patients with liver disease, and allergic reactions such as skin rash, hives, and swelling of the face, lips, tongue, or throat.

d. Contraindications

Paracetamol is generally safe and well-tolerated, but it is contraindicated in patients with a known allergy to the drug. It should be used with caution in patients with liver or kidney disease, and in patients who consume alcohol regularly.

e. Interactions

Paracetamol can interact with other drugs, including alcohol, anticoagulants, isoniazid, and phenytoin. These interactions may increase the risk of adverse effects, and patients should be advised to consult their healthcare provider before taking paracetamol with other medications.

In conclusion, paracetamol is a widely used pain reliever