Non-opioid Analgesics Without The Addition Of Acids

Non-opioid analgesics without the addition of acids are drugs that not only have analgesic but also antipyretic properties. Therefore, their application focuses mainly on the use of both of these activities.

Non-opioid analgesics consist of numerous substances with different mechanisms of action. In addition to typical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, they also include substances such as paracetamol and metamizole.

Drugs called non-opioid analgesics can be divided into two groups taking into account their main features:

• With acids. Non-steroidal anti-inflammatory drugs such as ibuprofen, acetylsalicylic acid and diclofenac.
• No added acids. Such as paracetamol and metamizole. It is these two drugs that we will consider in today’s article.

Although the mechanism of action of both groups of analgesics is generally based on the synthesis of prostaglandin, there are slight differences between them, which we will explain later.

Non-opioid analgesics without the addition of acids: paracetamol

Paracetamol is an analgesic belonging to the chemical group of anilines. It has the effect of reducing pain and fever. Therefore, it is mainly used to treat moderate pain and episodes of fever.

This painkiller was discovered in Germany in 1977. Nowadays, it is the most widely used painkiller in Europe and the United States to combat the aforementioned ailments. It is available as a generic drug and under many trade names such as Gelocatil® and Termalgin®.

Mechanism of action

Paracetamol does not have an anti-inflammatory effect, despite the fact that it affects the enzyme cyclooxygenase (COX), and yet it has an analgesic and antipyretic effect. This is because it only inhibits the action of COX-3, which is centrally located.

Therefore, inhibition of prostaglandin synthesis does not occur at the peripheral level and cannot exert anti-inflammatory effects. Prostaglandins are the molecules that make you feel pain. As acetaminophen prevents their synthesis, the pain threshold increases.

Moreover, when fever occurs, inhibition of prostaglandin synthesis increases. Thanks to the ability to inhibit COX-3, and thus the synthesis of these molecules, paracetamol lowers body temperature and thus reduces fever.

Side effects

The most important side effect of this pain reliever is its hepatotoxicity. It occurs when a drug is overdosed and the related waste products cannot be properly neutralized. Therefore, they influence the condition of the liver, leading to its necrosis.

In addition to hepatotoxicity, paracetamol may also cause the following side effects:

• Intolerance,
• Changes in how the kidneys work,
• Headaches,
• Uncertainty about what is happening
• Hypersensitivity.

Non-opioid analgesics without the addition of acids: metamizole

Metamizole belongs to the group of chemicals called pyrazolones. It treats fever and pain, just like acetaminophen.

It was developed in 1920 by German scientists. Nowadays, like all other analgesics, it is sold both under the generic name and under many other brands, such as Nolotil®.

Mechanism of action

Metamizole owes its antipyretic and analgesic properties to its ability to reduce inflammation-causing prostaglandin synthesis. It is able to do this by inhibiting prostaglandin synthetase. This enzyme is a catalyst, as the name suggests, for the synthesis of new prostaglandins.

In addition, metamizole is also able to inhibit fever caused by lipopolysaccharides. In addition, it has the effect of relaxing muscle contractions, which is associated with the inhibition of intracellular calcium due to reduced inositol phosphate synthesis.

Side effects of metamizole

Metamizole differs from other non-opioid analgesics that affect prostacyclin synthesis because it  does not cause any significant side effects related to the functioning of the digestive system.

However, as with all medications, it can also be associated with side effects. The most important of these are hypersensitivity reactions, such as:

• First of all, agranulocytosis. This is a serious side effect. This condition arises from a malfunction in the bone marrow that stops the body from producing enough white blood cells, or increases the destruction of white blood cells. Consequently, the level of white blood cells is lowered.

• Besides, leukopenia. This is a reduced number of leukocytes in the blood.
• And then thrombocytopenia. Increased number of platelets in the blood.

In conclusion, you should be aware of the importance of these medications in controlling conditions that cause inflammation and fever. These are two of the most commonly used anti-inflammatory drugs in the world.

However, like all drugs, they have significant side effects. You can protect yourself from most of them if you do not take them on your own and follow your doctor’s recommendations. If you have any doubts, consult your doctor or pharmacist.