Meclofenamate: What It Is And How It Works

Meclofenamate is a drug in the family of NSAIDs (non-steroidal anti-inflammatory drugs), a group of drugs widely used as analgesics. They also have anti-inflammatory and antipyretic effects (to lower fever).

Other drugs in this group are aspirin or ibuprofen. Its mechanism of action consists of the inhibition of the enzyme cyclooxygenase (COX). Among the NSAIDs, meclofenamate belongs to the group of fenamates. Its main applications are to alleviate menstrual pain or dysmenorrhea and joint stiffness of arthritis.

Mechanism of action of meclofenamate

Meclofenamate is an inhibitor of the enzyme cyclooxygenase (COX).  This enzyme has two isoforms:

• COX-1, constantly present in most tissues. This is what is called constitutive expression. It participates in various physiological mechanisms, such as platelet function, regulation of the cardiovascular system, and homeostasis.
• COX-2, whose synthesis is induced in certain circumstances, such as inflammation. In this case, it participates in the development of the cardinal signs of inflammation: edema (swelling), heat, redness and pain.

Cyclooxygenase participates in these processes by oxidizing arachidonic acid, present in the membrane of our cells. This oxidation gives different molecules:

• Thromboxanes.
• Prostaglandins.

These molecules are involved in multiple cellular processes. Among others, they are mediators of inflammation. The first is anti-inflammatory while the second is one of the promoters of the signs of inflammation.

In the inflammatory context, the released prostaglandins bind to certain receptors and are responsible for pain. They do this by lowering the threshold for pain-related nerve endings, which are called nociceptive endings.

In addition, they are involved in the edema that surrounds the inflammation by promoting vasodilation of the capillaries in the area. This vasodilation leads to an increase in vascular permeability, causing the blood plasma to go out into the extracellular space and causing swelling and a reddish color.

All these processes derive, among other things, from the oxidation of arachidonic acid by the enzyme cyclooxygenase. Meclofenate inhibits this enzyme, thereby inhibiting prostaglandin synthesis. For this reason it has anti-inflammatory effects.

They are also related to fever by binding to receptors in the central nervous system that are involved in thermoregulation, so NSAIDs also have an antipyretic effect.

Administration of meclofenamate

Meclofenamate is administered orally. It is recommended to take it with food or antacids to reduce possible stomach damage. Once ingested, it is absorbed quickly from the digestive tract. From there it passes into the blood, reaching the maximum concentration between 2 and 4 hours.

The metabolism of this drug takes place in the liver, through a process of oxidation and glucuronidation. Once metabolized, the elimination is mainly renal, with the urine; and a third is eliminated with the feces. This causes that in patients with hepatic and renal insufficiency it is necessary to adjust the dose and to be cautious with the use of this medicine.

It appears that the drug crosses the placental barrier during pregnancy, reaching the fetal tissues. Therefore, its use is contraindicated during it. It is also not recommended for use during lactation.

Indications of meclofenamate

There are many types of drugs in the group of NSAIDs, with different indications. Meclofenamate is indicated mainly in:

• Menstrual pain:  During menstruation, large amounts of prostaglandins are released into the uterine lining, causing contractions in the uterus. Their purpose is not to expel a fetus as in childbirth, but to facilitate the expulsion of the mucosa so that a new menstrual cycle can be restarted.
• Menorrhagia or heavy menstrual bleeding:  some NSAIDs can be used to decrease menstrual bleeding, such as meclofenamate.
• Joint inflammation: as we have explained, meclofenolato reduces both the inflammation and the pain associated with this type of process. Meclofenamate can be used in joint diseases such as ankylosing spondylitis, rheumatoid arthritis or osteoarthritis.
• Mild and moderate pain:  we have already said that prostaglandins are associated with the painful sensation that accompanies inflammation, so COX inhibitors can be used to alleviate it.

Adverse effects of meclofenamate

So far we have talked about the effects of meclofenamate by inhibiting the COX-2 isoform, as it is the most related to inflammatory processes. Meclofenamate also inhibits COX-1, from which the side effects of abuse of this type of medication derive.

The main complication of overuse of NSAIDs such as meclofenamate occurs in the stomach. Prostaglandins are protectors of the gastric mucosa against the hydrochloric acid that is synthesized in it.

If COX-1 is inhibited, prostaglandin synthesis decreases, increasing gastric secretion and decreasing mucosal protection. This alteration can damage the stomach wall causing gastroduodenal ulcers and stomach bleeding.

Other alterations associated with the use of NSAIDs are at the level of platelet function. Platelets use thromboxane A2 to stop bleeding, so an inhibition of COX-1 from platelets may increase the risk of bleeding.

Instead, COX-2 has the opposite effect, increasing the risk of vascular occlusion or thrombosis. The risk of each drug to produce one alteration or another depends on which isoform of the cyclooxygenase enzyme it inhibits with the greatest intensity.