Stomach upset? Can't digest food? Come on, let's talk about (Prokinetic Agents)!

Do you sometimes feel full or not digesting food properly after eating? Or do you have problems like heartburn or indigestion? Sometimes these problems can be caused by our intestines not working properly. Today we are going to talk about a special type of medicine that comes to the rescue at such times. These are called (Prokinetic Agents).

What are these (Prokinetic Agents)? Simply put...

Simply put, (Prokinetic Agents) are a type of medicine that increases the speed of food moving through your digestive system, that is, the intestines. When we swallow food, the muscles in our digestive tract start to contract from top to bottom like a series of waves. This is called (Peristalsis). It's like pushing food down. This is how food moves from the throat, down the esophagus, into the stomach, and then into the intestines. It's during this journey that our body absorbs the nutrients it needs.

However, due to some diseases or other reasons, this process called Peristalsis'' may not work properly. This is when symptoms such as constipation, heartburn, and feeling full without digesting food occur. Food may remain in the stomach for a long time, and then the body does not get the necessary nutrition.

That's when these drugs called (Prokinetic Agents) come to the rescue. These increase the movement of the intestines and help food pass down the digestive tract faster. But the most important thing to remember is that there are significant side effects that can come with these drugs. Therefore, doctors usually do not prescribe these drugs immediately. Most of the time, (Proton Pump Inhibitors - PPIs) or (H2 Blockers) are given other drugs and then (Prokinetic Agents) are considered only if they do not provide relief. However, depending on your medical condition, your doctor may also prescribe this drug.

How do these (Prokinetic Agents) work?

The way these medications work is a little complicated, but I'll keep it simple. They basically stimulate the nerves in your digestive system and help the muscles contract.

That means:

• It increases contractions in your esophagus (food pipe), helping to move food quickly into the stomach.
• Strengthen the Lower Esophageal Sphincter (LES) at the bottom of your esophagus. The LES is like a valve. It is the part of your esophagus that connects your stomach to your esophagus. If it doesn't close properly and becomes loose, stomach acid can come back up into your esophagus and throat. That's when you get that heartburn, heartburn, and chest pain. This is also called Acid Reflux or GERD.
• It increases stomach contractions and helps move food quickly into the small intestine.
• It reduces the time it takes for the stomach to empty. This reduces the chance of the contents of the stomach coming back up, like in the case of (Acid Reflux).

Imagine, this medicine acts like a traffic jam, and the police come and clear the way for the vehicles to move quickly.

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For what conditions are (Prokinetic Agents) used?

These medications are mainly used for the following conditions:

• Gastroparesis (stomach muscle dysfunction/delayed digestion): In this condition, the stomach muscles do not contract properly, so digestion of food is delayed. Prokinetic medications increase these contractions and cause the stomach to empty more quickly. People with diabetes can also develop this condition called Diabetic Gastroparesis. Metoclopramide is the only drug currently approved by the FDA in the United States for this. Your doctor may prescribe this if other treatments do not help.

• GERD (Gastroesophageal Reflux Disease): This is when stomach acid comes back up the esophagus into the mouth. This happens when the LES (Lessive Esophageal Suppression System) that I mentioned earlier doesn't close properly. Prokinetic agents alone won't help GERD. However, if your stomach is slow to empty, your doctor may prescribe these along with other medications.

• Functional Dyspepsia: This is when you have persistent stomach discomfort after eating, but no clear cause can be found. Some people may find that these medications can help reduce symptoms. Researchers say that these medications help by increasing stomach contractions and speeding up emptying.

• Nausea and vomiting: A doctor may prescribe this medication for acute or chronic vomiting that has not responded to other treatments. They are also sometimes used for vomiting caused by chemotherapy drugs for cancer.

• Chronic Intestinal Pseudo-obstruction: This is when the symptoms of a blockage are present even though there is no actual blockage in the intestine . Researchers are still investigating whether certain prokinetic agents can help with this condition.

What are the main types of (Prokinetic Agents)?

These drugs can be divided into two main categories: (Agonists) and (Antagonists).

• (Agonists): These act like certain (Neurotransmitters) (chemicals that carry messages between nerves) in our nervous system. That is, these (Agonists) go and attach to a nerve, telling that nerve to "contract". Just as the relevant (Neurotransmitters) does the same thing.
• (Antagonists): These work by preventing certain (Neurotransmitters) from binding to a nerve. Specifically, if there are (Neurotransmitters) that interfere with the (Peristalsis) process, these (Antagonists) block them from binding to the nerve.

These Prokinetic Agents'' are further divided into different categories, depending on how each drug works:

• (Cholinergic Agonists):These work like a (Neurotransmitter) called (Acetylcholine). (Acetylcholine) stimulates the contraction of the muscles in the intestines. Examples: (Baclofen), (Bethanechol), (Neostigmine), (Pyridostigmine).
• (Motilin Agonists) (Macrolide Antibiotics): These work like the (Neurotransmitter) called (Motilin). (Motilin) stimulates contractions in the small intestine. Some drugs in this group are actually (Antibiotics) that are given to treat bacterial infections. Examples: (Erythromycin), (Azithromycin).
• Serotonin Agonists: These work like the neurotransmitter serotonin. Like serotonin, they stimulate intestinal contractions and help the stomach empty. Examples: Cisapride, Prucalopride, Tegaserod.
• (Dopamine Antagonists): These prevent the (Neurotransmitter) called (Dopamine) from binding to nerve cells. (Dopamine) reduces the movement of the stomach and intestines, and also relaxes the (LES). So, when (Dopamine) stops binding, these (Dopamine Antagonists) reverse that effect (i.e. increase movement). Examples: (Metoclopramide), (Domperidone).

Some examples of (Prokinetic Agents)

There are currently some types of Prokinetic medications that are used for treatment, some of which have been banned in countries like the United States due to side effects, and some that are still in the research stage.

• Azithromycin (Zithromax®): A motilin agonist. Doctors sometimes prescribe it off-label for gastroparesis.
• Baclofen (ED baclofen®): A cholinergic agonist. Its benefits for GERD are still being studied.
• (Bethanechol) (Urecholine®): A (Cholinergic Agonist). It helps with (Gastroparesis) and (GERD) symptoms. However, it is not used in large quantities because it can cause serious side effects such as muscle spasms and blurred vision.
• Cisapride (Propulsid®): A serotonin agonist. Helps the stomach empty more quickly. Previously used for GERD. Removed from the US market due to heart-related side effects.
• (Domperidone) (Motilium®): A (Dopamine Antagonist). In the United States, it is not easily available without special permission. It can cause serious heart problems such as irregular heartbeat and heart attack.
• Erythromycin (EES®): A Motilin Agonist. A doctor may prescribe it off-label for gastroparesis.
• Metoclopramide (Reglan®, Maxeran®, Gimoti®): A dopamine antagonist. The only FDA-approved drug for gastroparesis. It is also used to treat GERD that has not responded to conventional treatments. However, it comes with a warning that it can cause side effects that affect the nervous system.
• (Prucalopride) (Motegrity®):A (Serotonin Agonist). It is given for chronic constipation. It also helps the stomach empty quickly.
• Pyridostigmine (Mestinon®): A cholinergic agonist. It is primarily used to treat Myasthenia Gravis, but is also sometimes used to treat Gastroparesis.

What are the side effects of using these (Prokinetic Agents)?

This is the most important thing to be careful of. Prokinetic agents can have serious side effects. That's why doctors are often reluctant to prescribe them. However, when conventional treatments like PPIs for GERD don't work, a doctor may decide to prescribe a prokinetic agent. Or, as a precaution, they may be prescribed in a lower dose or for a shorter period of time.

If a doctor prescribes a prokinetic agent for you, be sure to ask about the specific side effects of that medication.

Common side effects include:

• Stomach ache
• Nausea and vomiting
• Diarrhea (bloating)
• Blurred vision
• Headache (headache)
• Tiredness
• Drowsiness, excessive fatigue, frequent sleepiness (Lethargy)
• Depression
• Anxiety
• Uncontrolled muscle contractions (Dystonia)
• Uncontrolled facial muscle movements (Tardive Dyskinesia)

Drugs like (Cisapride), (Domperidone) and (Tegaserod) were removed from the market due to the risk of serious heart problems. That is:

• Slow heart rate (Bradycardia)
• Irregular heartbeat (Arrhythmia)
• Heart attack

Current research into new prokinetic agents is focused on developing drugs that offer the benefit of stimulating intestinal contractions while reducing the risk of such side effects.

What are the most commonly used (Prokinetic Agents)?

The most commonly prescribed prokinetic agents are Metoclopramide and Domperidone. In the United States, Metoclopramide is the only FDA-approved drug for gastroparesis. However, a doctor can prescribe Domperidone with FDA approval.

Prokinetic agents vary in their effectiveness and safety in treating digestive disorders. Because of the risk of side effects, a doctor may try other medications before prescribing a prokinetic agent. However, if you have severe symptoms because your bowels are not contracting properly, a prokinetic agent may provide much-needed relief. If you are considering taking a prokinetic agent, it is important to discuss the benefits and risks with your doctor.