Non-acidic, Non-opioid Painkillers

Non-opioid analgesics include different types of substances with different mechanisms of action. In addition to the typical non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors  , substances such as paracetamol or acetaminophen and metamizole also belong to this group.

We can classify non-opioid painkillers based on their chemical characteristics:

• Acid. NSAIDs such as ibuprofen, acetylsalicic acid and diclofenac.
• Non-acid. Such as paracetamol or acetaminophen and metamizole. These are two drugs we will focus on in this article.

Although the mechanism of action for both groups of analgesics generally lies in the synthesis of prostaglandin,  there are minor differences, which we will explain below.

Non-acid and non-opioid analgesics: Paracetamol or acetaminophen

Paracetamol is a painkiller that belongs to the chemical group of aniline. It has analgesic and antipyretic properties. It is therefore used primarily in the treatment of moderate pain and episodes of fever.

This painkiller was discovered in Germany in 1877. Today, it is the most widely used painkiller in Europe and the United States for the indications we mentioned above. It is available as a generic drug and under various brands such as Panodil®.

Mechanism of action

The reason paracetamol is not anti-inflammatory but is analgesic and antipyretic, despite the fact that it acts on the cyclooxygenase enzyme (COX),  is that it only inhibits COX-3, which is centrally located.

Prostaglandin is therefore an inhibitor of synthesis, which does not take place at the peripheral level, and it can not act as an anti-inflammatory agent. Prostaglandins are the molecules that are responsible for the feeling of pain. Since it inhibits the synthesis of it, the pain threshold increases.

In conditions of fever, in addition, the inhibition of prostaglandin synthesis is increased.  Since it inhibits COX-3 and thus also the synthesis of these molecules, paracetamol lowers the body temperature and thus also the fever.

Side effects of paracetamol

The main side effect of this type of painkiller is its hepatoxicity. This happens when there is an overdose of the drug and the metabolites that occur as a result cannot be properly neutralized. They thus affect the liver, causing liver failure.

The toxic metabolite from the conversion of paracetamol is called NAPQI or Nacetyl-p-benzoquinoneimine, which is neutralized with glutathione reserves.

In addition to hepatoxicity, it can also trigger other side effects such as:

• Intolerance.
• Changes in renal function.
• Headache.
• Confusion.
• Hypersensitivity.

Non-acidic, non-opioid analgesics: Metamizole

Metamizole belongs to the chemical group of pyrazolone. Just like paracetamol, it treats fever and pain.

German experts synthesized it in 1920. Today, like all other types of painkillers, it is marketed under the generic name and various brands such as Nolotil®.

Mechanism of action

Metamizole derives its antipyretic and analgesic effect from its ability to reduce pro-inflammatory synthesis of prostaglandin. This is because it is able to inhibit the synthesis of prostaglandin. This enzyme catalyzes, as its name suggests, the synthesis of new prostaglandins.

In addition, metamizole is also able to inhibit lipopolysaccharide-induced fever. In addition, it has anticonvulsant effects, which are associated with the inhibition of intracellular calcium as a result of the reduced synthesis of inositol phosphate.

Side effects of metamizole

Metamizole is different from non-opioid analgesics, which act on the synthesis of prostacyclin, in that  it does not cause any significant side effects for the gastrointestinal tract.

However, like all other drugs, it produces other side effects. The most important are those related to hypersensitive reactions such as:

• First, there is agranulocytosis. It is a serious side effect. It is a disorder that comes from a lack of bone marrow that does not allow the body to produce enough white blood cells or increase the destruction of white blood cells. As a result, there is a low number of white blood cells.
• In addition, there is also leukopenia. A reduced number of white blood cells in the blood.
• As the latter, there is thrombocytopenia. A reduced number of platelets.

In short, one should keep in mind the importance of these drugs in controlling diseases that cause processes of inflammation and fever, representing two of the most widely used anti-inflammatory drugs in the world.

Like all other medicines, however, they have significant side effects. You can prevent most of them if you do not self-medicate and respect the treatment prescribed by your doctor. If you have any further questions on the use of this product, talk to a doctor or pharmacist.