Paracetamol exhibits analgesic and antipyretic properties. The mechanism of action of paracetamol has not been fully elucidated; some sources suggest it reduces prostaglandin synthesis through indirect inhibition of cyclooxygenase activity distinct from the previously described COX-1 and COX-2 isoforms. Unlike nonsteroidal anti-inflammatory drugs (NSAIDs), it does not decrease peripheral prostaglandin synthesis and therefore does not exert anti-inflammatory effects. Paracetamol also has no effect on platelet aggregation and lacks the adverse effects typical of NSAIDs.
The analgesic mechanism of action involves reduction of arachidonic acid cyclooxygenase activity. This results in decreased prostaglandin production in the central nervous system, leading to an elevation of the pain threshold. The decrease in prostaglandin concentration in the hypothalamus, where the thermoregulatory centre is located, is responsible for the antipyretic effect of paracetamol.
Paracetamol is well absorbed from the gastrointestinal tract. Its oral bioavailability is approximately 90%. Food may reduce the absorption of the drug. Peak plasma concentration of paracetamol is reached approximately one hour after administration. Following rectal administration, peak plasma concentration occurs 2–3 hours after administration.
Paracetamol undergoes minimal protein binding. After administration of a therapeutic dose, 10 to 20% of paracetamol was found in a protein-bound form.
Paracetamol primarily undergoes three types of biotransformation in the liver: conjugation with glucuronic acid; conjugation with sulfuric acid; oxidation via cytochrome P450 subunits, leading to the formation of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Normally, when paracetamol is used at recommended doses, NAPQI is rapidly conjugated with glutathione and undergoes further metabolism before being excreted. A problem arises when paracetamol is taken in a dose that leads to excessively rapid depletion of glutathione stores, or when these stores have been diminished due to excessive alcohol consumption. In such cases, levels of hepatotoxic NAPQI may reach dangerously high values.
The half-life of paracetamol, depending on individual characteristics, ranges from 2 to 4 hours. In cases of paracetamol overdose, the half-life may increase up to 8 hours depending on the degree of liver damage. Only 5% of the dose is excreted unchanged in the urine.
⚠️ Warnings
Paracetamol should be used with caution in patients with alcohol dependence and in malnourished patients due to the risk of liver damage.
During the use of paracetamol, particular attention should be paid to the total amount of the active substance taken across different preparations. The popularity of paracetamol among manufacturers of medicinal products in various forms (sachets, tablets, suppositories, suspensions) facilitates inadvertent overdose.
Some patients with hypersensitivity to acetylsalicylic acid may also exhibit hypersensitivity to paracetamol.
Caution should also be exercised in patients with congenital glucose-6-phosphate dehydrogenase deficiency or methaemoglobin reductase deficiency.
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