Paracetamol

Paracetamol is an active substance with antipyretic and analgesic effects. It belongs to the group of non-opioid analgesics and is one of the most widely used medicines in the world. It is used in adults and children to treat mild to moderate pain and fever. Paracetamol is mainly known as acetaminophen in the US and is also on the WHO's list of essential medicines. In most cases, it is available, alone or in combination with other active ingredients, as an over-the-counter product without a prescription.

Paracetamol can be administered in the form of suppositories, tablets, effervescent tablets, capsules, hard capsules, syrup, juice, granules as well as an infusion solution.

Pharmacodynamics

The exact mechanism of action of paracetamol has not been completely elucidated to date. Unlike the analgesics of the non-steroidal anti-inflammatory class, it has little inhibitory effect on the enzymes cyclooxygenase 1 and 2, which play an important role in the development of the sensation of pain. Studies showed that paracetamol probably blocks another isoform of this enzyme, cyclooxygenase 3. This results in indirect inhibition of pain. The antipyretic effect of paracetamol is probably achieved through an effect on thermoregulation of the brain and spinal cord. However, some further research is required to elucidate the exact mechanism of action.

Pharmacokinetics

After oral administration (absorption by mouth, for example in the form of a tablet), it usually takes 30-90 minutes for the maximum blood plasma concentration to be reached. Oral bioavailability is approximately 88% and plasma half-life is 1-4 hours. Plasma protein binding at therapeutic doses is comparatively low at 10-25%. Paracetamol is mainly degraded in the liver. This occurs first by the cytochrome P450 system and subsequently by conjugation (coupling) with glucuronic acid or sulfate and then with gluatathione. Excessive doses of the drug can cause complete consumption of glutathione, resulting in very rapid damage to liver tissue. The final metabolites of paracetamol are eventually excreted in the urine.

Drug Interactions

The two active substances probenecid and salicylamide can slow down the excretion of paracetamol and thus promote possible liver damage. Alcohol and medicines which are considered to be so-called CYP450 inducers (e.g.: carbamazepine, barbituric acid) may also promote the formation of liver-damaging substances. Drugs with an effect on the gastrointestinal tract can slow down the absorption of paracetamol and thus limit its effectiveness.

Paracetamol itself rarely shows effects on the efficacy of other medicines. Paracetamol may increase the effect of anticoagulants when taken regularly. In addition, paracetamol is known to further potentiate the blood count-altering effect of zidovudine. It is also suspected that paracetamol can suppress the effectiveness of vaccinations. Therefore, it is not recommended to take it before and after vaccination.

In case of overdose, kidney or liver damage, hypoglycemic coma or thrombocytopenia may occur. In particularly severe cases, liver failure is also possible.

In long-term studies, evidence was found that acetaminophen may induce monocyte leukemia in female mice in rare cases. However, the applicability of this study to humans has not been established.

There is no evidence that paracetemol has a mutagenic effect or influence on fertility.

Paracetemol may pass into breast milk and should therefore be taken by pregnant women and nursing mothers only on the express instructions of a doctor.

Side effects

Undesirable side effects are rare if paracetemol is used properly. Possible side effects include blood count changes, skin reactions and elevation of liver enzymes.

Toxicological data:

LD50= 338 mg/kg (oral, mouse), LD50 = 1944 mg/kg (oral, rat).