Currently for acid-related digestive tract diseases, azole drugs (proton pump inhibitor PPI) is currently the most commonly used drugs in clinical practice, this type of drug for the inhibition of gastric acid is clear, effective, so many friends have acid reflux, stomach upset symptoms, will take azole drugs to relieve, and even a lot of friends perennial taking azole drugs, in fact, do so is very undesirable.

Several recent studies have found that long-term use of azoles has the potential to increase the risk of hepatocellular liver cancer incidence, and in June 2018, results of a study from the University of Taipei showed that in a long-term follow-up of nearly 60,000 people from 2000 to 2013, the incidence of hepatocellular liver cancer was found to be 2.86 times higher in patients with long-term use of PPIs compared to the control group.

And a recent joint UK-US study involving 470,000 people and spanning more than 18 years also found that long-term use of omeprazole was associated with a significant increase in the odds of risk of liver cancer, while long-term use of H2 receptor antagonists (tilden analogs) had a lesser effect.

Regarding the principle of action of omeprazole that may cause the risk of liver cancer, a study published in Nature found that PPIs inhibit gastric acid secretion, leading to the proliferation of enterococci, which are able to enter the liver and cause damage to liver health.

In addition to PPIs being associated with an elevated chance of liver cancer with long-term use, the issue of PPI preparations being used for long periods of time and potentially causing gastric cancer is also gaining traction, with a 2017 study from the Faculty of Medicine at the University of Hong Kong finding a more than seven-fold increase in the risk of gastric cancer with long-term use of PPIs.

In the case of excessive gastric acid secretion, PPI inhibits gastric acid secretion and can effectively relieve many symptoms of diseases related to excessive gastric acid caused by gastric acid, in the treatment of peptic ulcers, in the eradication program of Helicobacter pylori, the PPI drug of the class of azole is an essential medication, but the drug itself is a double-edged sword, if the application of a reasonable, it can be minimized to minimize the impact of its impact on the body's health, while the If it is not used wisely, it may increase the chances of side effects or significant impact on the body.

The azole drug is a good example, so many studies show that long-term use of azole drugs lead to an increase in the chances of cancer, then azole can still eat? Of course, if the disease really need, should eat or eat, to give you a few examples:

1. Patients with H. pylori positive duodenal ulcers undergo H. pylori eradication treatment with a quadruple combination of drugs (including azoles) for 2 weeks and continue acid suppression therapy [Take a PPI (before breakfast) + a tilden (Take it after dinner.）] for 2 weeks to stop taking arazoles;

2. Helicobacter pylori positive gastric ulcer patients, Helicobacter pylori eradication medication for 2 weeks, continue acid-suppression therapy for 4 to 6 weeks, you can stop taking azoles;

3. For H. pylori-negative duodenal ulcer patients, it is recommended to discontinue azoles after 4 weeks of acid-suppressive therapy and to take tilden after dinner every day for the next 12 weeks for maintenance therapy, whereas for gastric ulcer patients it is usually recommended to discontinue acid-suppressive therapy after 6-8 weeks of acid-suppressive therapy and then to take maintenance therapy for the next 12 weeks.

4. Patients who need long-term aspirin to prevent blood clots, if there are gastrointestinal problems or Helicobacter pylori positive, it is recommended to carry out the eradication of Helicobacter pylori treatment first, after the end of the eradication treatment in the taking of aspirin, in the first 12 months of taking, the first 6 months to take azole drugs to protect the gastric mucosa, reduce the risk of gastrointestinal bleeding, 6 months, can be switched to tetrodotylate drugs, continue to take 6 months. .

These are the classic dosing regimen for the application of arazoles, and not considered a long-term use of the situation, are safe and effective treatment of the disease, but still emphasize that it is not recommended that the adult long-term use of omeprazole to inhibit the secretion of gastric acid, may really lead to liver cancer, gastric cancer increased risk of incidence of the disease, the benefits do not outweigh the costs.

Omeprazole, rabeprazole, and lansoprazole are proton pump inhibitors that have a powerful ability to inhibit gastric acid, and are commonly used in clinical practice, and even abused in some cases. Therefore, research on proton pump inhibitors has been proliferating.

There are indeed some studies that suggest that long-term use of proton pump inhibitors such as omeprazole may lead to an increased risk of liver cancer. There is a study in the United Kingdom, collected the medical records of patients using proton pump inhibitors from 1993-2011, in addition, also collected 470,000 people's data from UK BIOBANK, through the control analysis, excluding confounding factors, surprisingly, found that the use of proton pump inhibitors to get an 80% increase in the risk of liver cancer compared with the control group, of which the risk of omeprazole is 83%, and the risk of lansoprazole is 34%. Of course, these studies have their limitations and need to be verified by further and more rigorous experiments.

Why proton pump inhibitors may increase the risk of liver cancer.

The main reason may be the ability of proton pump inhibitors to cause hypergastrinemia, and liver cells are more affected by this. In addition, the inhibition of gastric acid leads to the growth of intestinal flora, which increases bile acid secretion, and this affects the secretory function of the liver. Some studies have found that proton pump inhibitors may accelerate the progression of cirrhosis to liver cancer.

There is also research on the increased risk of stomach cancer with proton pump inhibitors, finding that long-term use of omeprazole, for example, may increase the risk of stomach cancer by as much as two-fold, and that the risk is positively correlated with the dose and duration of use.

Omeprazole, lansoprazole and other proton pump inhibitors are very effective for diseases caused by excessive secretion of gastric acid, which is indeed a good drug, and short-term use generally does not have any major side effects. However, it is not recommended to use them for a long period of time, especially if they are used for several years or decades, which will not only increase the risk of liver and stomach cancer, but also increase the risk of cardiovascular, cerebral and cerebral vascular diseases, osteoporosis and other related diseases.

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This is a very good question! Proton pump inhibitors, abbreviated as PPIs, are another important class of drugs that inhibit gastric acid secretion following H2 receptor antagonists, and are currently the most potent class of drugs that inhibit gastric acid secretion.

The common proton pump inhibitors in clinical practice today are omeprazole, rabeprazole, lansoprazole, pantoprazole and esomeprazole to name a few.

Proton pump inhibitors, which are used clinically for the treatment of peptic ulcer, gastroesophageal reflux disease, Dreiemann's syndrome, and upper gastrointestinal bleeding.

Proton pump inhibitors, which are now the first-line drugs for clinical abnormalities of gastric acid secretion and related disorders, are also used in combination with amoxicillin and clarithromycin for the eradication of Helicobacter pylori infection.

Common adverse reactions to proton pump inhibitors include: nausea, flatulence, diarrhea, constipation, epigastric pain, and other digestive system and so on.

Occasionally, a rash, elevated alanine aminotransferase (ALT) and bilirubin are seen, but they are usually mild and transient, and most do not affect treatment.

As for long-term use of proton pump inhibitors, does it increase the risk of stomach and liver cancer?It has long been controversial in academia, but has not yet been confirmed by evidence-based medicine.

In the following, I will make a brief communication with you guys from the mechanism of action of proton pump inhibitors and the controversial situation about the increased risk of gastric cancer by PPIs, and due to the space, this communication will not be discussed for the risk of liver cancer.

Mechanism of action of proton pump inhibitors

Where does our stomach acid come from? The stomach acid in our stomach is in the cell membranes of the stomach wall"H+, K+-ATPase "pump moleculesThe action pumps intracellular H+ out into the stomach in the form of H+ to K+ exchange, and the H+ (hydrogen ions) is stomach acid.

When we take a proton pump inhibitor such as omeprazole, the drug is first absorbed into the bloodstream, but then diffuses into the cells of the human stomach lining, where it binds to the "H+, K+-ATPase" pump molecule, irreversibly causing thepump molecular inactivation, resulting in less stomach acid as intracellular H+ (hydrogen ions) cannot be pumped in and out of the stomach.

Only if the new "H+, K+-ATPase" pump moleculeresynthesizeout and inserted again into the cell membrane of the stomach wall before it can beRestart the pumpfunction of pumping H+ into the stomach before gastric acid secretion begins again.

Since proton pump inhibitors, act on the last link in gastric acid secretion, their inhibition of gastric acid is powerful and long-lasting.

However, despite being acid-producing agents, proton pump inhibitors are inherently acid-intolerant and are easily broken down and destroyed by stomach acid.

Therefore, proton pump inhibitors, except for injections, oral formulations, mostly in enteric form, are transported to the alkaline-biased intestinal tract for absorption to avoid disruption of the gastric acid environment.

Academic controversy over PPIs' increased risk of gastric cancer

The main academic controversial view that proton pump inhibitors (PPIs), can increase the risk of gastric cancer is.Long-term use of PPIs can lead to an increase in serum gastrin levels, which has the potential to promote gastric mucosal cell proliferation (origin of gastric cancer), so long-term use of PPIs has an increased risk of gastric cancer.

1. In 2013, Seoul National University Hospital in South Korea showed through meta-analysis (statistical method) that acid suppressants, such as PPIs, may increase the risk of gastric cancer

2. Prof. Leung Wai-keung's team at the University of Hong Kong published a statistical analysis of data in the journal GUT (the official journal of the British Society of Gastroenterology), showing that long-term use of PPIs can increase the risk of gastric cancer, and the risk of gastric cancer increases with the duration of the application of PPIs and with the increase in the dose of PPIs, respectively.

3. Two Norwegian academics have supplemented the above study by Prof. Leung Wai-keung's team at the University of Hong Kong as follows.

They believe that because long-term use of PPIs causes a low-acid environment in the stomach, it promotes the elevation of gastrin under the action of negative feedback mechanism, which makes gastrin act on the gastrin receptor of the gastric mucosa and stimulates the proliferation of gastric mucosal cells, resulting in the formation of neuroendocrine tumors and even gastric cancer, and said that this process, they have been confirmed in animal experiments.

In conclusion, so far, the information about long-term use of proton pump inhibitors, which increases the risk of gastric cancer, is still in the stage of doctrinal controversy and has not been confirmed by evidence-based medicine.

What patients should do in the face of PPI controversy

Nowadays, both clinicians and patients themselves, proton pump inhibitors (PPIs) seem to have long been deeply rooted in people's hearts, as if they had become the "essential oils" of gastroenterologists; they have become the "gastric necessities" of ordinary people's homes!

So what do we do in the face of proton pump inhibitors (PPIs) that are controversial on one side and inseparable on the other?

It is recommended to grasp 2 key points: first, the dosage is strictly in accordance with the doctor's instructions, under the guidance of the doctor; second, the drug is strictly in accordance with the dosage contained in the drug instructions, specific examples are as follows.

1. Omeprazole instruction dosage

(1) Duodenal ulcer: Oral, 20mg once daily for 4-6 weeks.

(2) Gastric ulcer: Oral, 1 time 20mg, once a day, course of treatment 6-8 weeks.

2. Rabeprazole instructions dosage

(1) Duodenal ulcer: Oral, 10-20mg once daily for 4-6 weeks.

(2) Gastric ulcer: take orally, 10-20mg once a time, once a day, for 6-8 weeks.

3. Lansoprazole instruction dosage

Gastric and duodenal ulcers, reflux esophagitis: Adults usually take 30mg orally once a day in the early morning.

(1) Duodenal ulcer: Oral, 30mg once a day for 4 weeks.

(2) Gastric ulcer:Oral, 30mg once a day for 4-6 weeks.

Clinicians should be proactively alerted to any discrepancy between the clinician's prescribed dosage and the dosage stated in the drug insert.

To summarize:As of today, information about long-term use of proton pump inhibitors (PPIs), which increase the risk of gastric cancer, is still in the stage of doctrinal controversy and has not been confirmed by evidence-based medicine.

As an ordinary citizen, when taking proton pump inhibitors, there are 2 key points to be grasped: firstly, the dosage is strictly in accordance with the doctor's prescription and under the doctor's guidance; secondly, the dosage is strictly in accordance with the dosage set out in the instruction manual of the drug.

Clinicians should be proactively alerted to any discrepancy between the clinician's prescribed dosage and the dosage stated in the drug insert.

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Proton pump inhibitors (PPIs) irreversibly bind to and inhibit the activity of the hydrogen-potassium (H-K) ATPase pump at the luminal surface of the cell membrane of the gastric wall, thereby effectively blocking gastric acid secretion. However, long-term application of PPIs may lead to some safety-related problems and is a concern for some of the drug-using population. There is very little consistent data on causality to support these concerns regarding the idea of an increased risk of gastric and hepatic cancer after long-term PPI use.

In vivo induction of hypergastrinemia has been associated with gastric carcinoid tumors in rats in animal studies, but these observations do not describe or speculate on the human disease situation. Although some intestinal chromophobe hyperplasia has now been identified in patients treated with omeprazole for up to 11 years, no heterogeneous hyperplasia or neoplastic changes have been observed [1]. It has not been established that hypergastrinemia causes an increased risk of colon cancer.

Prolonged use of PPIs can cause associated adverse effects, and the following are those that are currently confirmed in studies or those that need to be further confirmed:

1. PPI use is associated with an increased risk of Clostridium difficile infection, other intestinal infections, and microscopic colitis.

2. PPIs can cause hypomagnesemia by decreasing intestinal magnesium absorption. Prolonged use of PPIs can cause vitamin B12 malabsorption.

3. Although the use of PPIs may be associated with fractures, a causal relationship has not been demonstrated, and PPIs may reduce the absorption of non-water-soluble calcium (e.g., calcium carbonate).

4. The use of PPIs is also associated with an increased risk of new-onset chronic kidney disease (CKD), progression of CKD and end-stage renal disease.

5. The available data on the association of PPI use with the risk of dementia and pneumonia are inconsistent.

References:

Klinkenberg-Knol EC, Nelis F, Dent J,et al. Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa.Gastroenterology. 2000;118(4):661.

Na Cun, Clinical Pharmacy Office, Affiliated Hospital of Chifeng College, Member of the Pharmacy Network

The authoritative interpretation of Pharmaceutical Affairs, unauthorized reproduction, plagiarism will be punished.

Omeprazole, rabeprazole, lansoprazole, pantoprazole, etc. are dead belong to the proton pump inhibitor, has a powerful inhibition of gastric acid. Mainly used for gastric ulcer, duodenal ulcer, reflux esophagitis, eradication of Helicobacter pylori treatment, but also a part of the patients long-term taking proton pump inhibitors to relieve acid reflux, heartburn and other symptoms, some patients a drug is long-term for several years, then proton pump inhibitors long-term taking in the end what are the risks?

1. Long-term use of proton pump inhibitors will lead to too little gastric acid secretion: when the stomach acid is reduced by the long-term role of drugs, it will lead to a decrease in gastric acid, and after too little gastric acid, for the intestinal bactericidal effect will be weakened, increasing the risk of intestinal infections, and the gastric acid can also promote the absorption of some nutrients, such as vitamin B2, iron, etc., if the gastric acid is too little, it will affect the absorption of these nutrients, resulting in malnutrition. If the stomach acid is too low, it will affect the absorption of these nutrients and cause malnutrition.

2. Long-term use will lead to the risk of chronic atrophic gastritis: atrophic gastritis is mainly a reduction in gastric acid secretion, a study has pointed out that patients with Helicobacter pylori infection, long-term use of proton pump inhibitors, the risk of atrophic gastritis is significantly higher than that of the patients who do not have Helicobacter pylori infection.

3. Precautions for the use of proton pump inhibitors: when using proton pump inhibitors for the treatment of gastric and duodenal ulcers, the possibility of gastric cancer must be ruled out first, or else it may lead to the masking of the condition and delay in treatment. There is also the use of proton pump inhibitors in pregnant and lactating women with caution, severe hepatic insufficiency should be used when the dose should be reduced by half.

There are no definitive research data on whether long-term use of proton pump inhibitors increases the risk of liver cancer.

These are the views of Xiao Ke, welcome your questions and additions, pay attention to Xiao Ke, to learn more about health knowledge.

Omeprazole, rabeprazole, and lansoprazole belong to the PPI class of drugs, or proton pump inhibitors, which are drugs that inhibit gastric acid secretion. These three drugs are in the same broad class of drugs and are widely used clinically, especially omeprazole.

These drugs treat diseases mainly gastric ulcer, duodenal ulcer, reflux esophagitis, etc., these diseases have excessive secretion of gastric acid, so it leads to easy ulcers, we used to think that there is no acid without ulcers, the reason why gastric ulcers have gastric ulcers is because of the excess of gastric acid, so inhibiting gastric acid secretion can treat gastric ulcers, in the past when there were no such azoles, the effect of the treatment of many gastric ulcers by drugs was Not very good, a lot of still need surgical treatment, directly to most of the stomach cut off, later with this kind of azole drugs, surgical operation is done less, because the drug inhibit gastric acid secretion effect is very good, gastric ulcers, duodenal ulcers healing rate is very high.

Can these drugs be so effective that they cause cancer? No, at least not according to current research. Long-term use is not usually necessary, usually for a few months, and the medication can be discontinued after the ulcers have healed. The main clinical adverse reactions are allergic reactions (skin irritation, itching), jaundice, liver function abnormalities, interstitial pneumonitis, blood cell reduction, gastrointestinal symptoms (e.g., nausea, vomiting, abdominal distension, constipation, diarrhea), etc. No studies have shown that this type of medication increases the risk of gastric cancer or liver cancer.

On the contrary, a part of patients with gastric ulcers (5%) will become cancerous, or they are originally gastric cancer, only masked by gastric ulcers. The effect of these drugs may not be very good or may be easily repeated. At this time, if stomach cancer is found, it cannot be simply thought that it is caused by these drugs.

As for liver cancer, the well-known factors are hepatitis B, alcohol, etc. The vast majority of liver cancer patients in China have progressed from hepatitis B. There is no relationship with this kind of drugs, at least the current research has not found a relationship.

So if you need to use this type of medication, you don't need to have a psychological burden, you should still use it, these are better medications.

Omeprazole, rabeprazole and lansoprazole are commonly used in the clinic for acid inhibition, belonging to the proton pump inhibitors, which we are also used to call "razole" type of drugs, they are used to inhibit gastric acid secretion by blocking the proton pump on the cells of the gastric lining, acting in the last link of gastric acid secretion, with strong acid inhibition, and it can bring acid-free level to the stomach for a long time up to 72 hours. Acid-free level, acid inhibition for a long time, up to 72 hours, for gastric and duodenal ulcers, functional dyspepsia, gastroesophageal reflux disease, as well as Zuo - Ai syndrome and other gastric acid-related disorders, and prevention and treatment of non-steroidal anti-inflammatory drug-associated ulcers, but also enhance the bactericidal effect of antibiotics against Helicobacter pylori for the joint eradication of Helicobacter pylori.

For common acid-related diseases, such as gastroesophageal reflux disease (GERD) and gastric and duodenal ulcers, azoles should be used for as short a time as possible, usually for 4-8 weeks. Recurrent GERD requires long-term use of azoles to reduce heartburn and acid reflux, minimize recurrence of esophagitis, and prevent esophageal strictures. In addition, patients with Barrett's esophagus also need to take long-term "azole" drugs, which can reduce the symptoms of reflux and delay the progression of Barrett's esophagus to esophageal cancer, asymptomatic patients with Barrett's esophagus are not recommended to take "azole" drugs for a long period of time. It is not recommended for patients with asymptomatic Barrett's esophagus to take "razole" drugs for a long time. Lastly, patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and diclofenac sodium, antiplatelet agents such as aspirin and clopidogrel, or glucocorticosteroids such as prednisone and dexamethasone also need to combine with azoles to prevent ulcer disease and reduce the risk of rebleeding from ulcers.

Prolonged use of drugs such as azole, which continues to inhibit gastric acid secretion, may increase the risk of adverse effects such as lung infection, abdominal infection, impaired nutrient absorption, bone fracture, acute kidney injury and dementia. In addition, it has been found that "azole" drugs can weaken the secretion of growth inhibitor by gastric sinus cells, promote the release of gastrin, leading to hypergastrinemia, increased gastrin can lead to tissue atrophy and stimulate the growth of tumor cells, and animal experiments have proved that hypergastrinemia can lead to the growth of intestinal chromaffin cells, promote the development of carcinoid tumors and neuroendocrine tumors, and increase the incidence of gastric cancer and neuroendocrine tumors. There are animal experiments confirming that hypergastrinemia can lead to the growth of intestinal chromophobe cells, promote the occurrence of carcinoid and neuroendocrine tumors, and increase the risk of malignant tumors such as gastric cancer, colon cancer, and esophageal adenocarcinoma, etc. However, there is no sufficient evidence confirming that the long-term use of "razole" type of drugs can lead to malignant tumors for human beings.

In conclusion, omeprazole, rabeprazole and lansoprazole are commonly used acid-suppressing drugs in the clinic, which we also call "azole" drugs, applicable to gastric and duodenal ulcer, functional dyspepsia, gastroesophageal reflux disease and other gastric acid-related disorders, and can be used in conjunction with antibiotics to eradicate Helicobacter pylori. Patients with recurrent gastroesophageal reflux disease, Barrett's esophagus, and long-term use of non-steroidal anti-inflammatory drugs, antiplatelet agents, and glucocorticoids need to take "azole" drugs for a long period of time, and long-term use of these drugs may increase the risk of lung infections, abdominal cavity infections, nutrient absorption disorders, bone fracture, acute kidney injury, dementia, and adverse reactions such as gastrointestinal malignancies. However, it has not been proven that long-term use of azoles can lead to gastrointestinal malignant tumors in humans.

To answer this question let's look at two pieces of information.

First, omeprazole treatment of Helicobacter pylori can significantly reduce the incidence of gastric cancer.

On September 14, 2019, the leading international British Medical Journal, in its Volume 366, Issue 8213, published the results of the follow-up of a clinical trial on the effect of omeprazole, treatment of Helicobacter pylori, on mortality from gastric cancer incidence.

This is a trial in which 3,365 residents of areas with a high incidence of stomach cancer were treated with H. pylori for a period of two weeks and continued to be observed for more than 22 years in a trial that lasted 22 years from 1995 to 2017, and found that treatment of H. pylori with omeprazole significantly reduced the incidence of stomach cancer.

Second, omeprazole, pantoprazole, and lansoprazole, which can increase the risk of glandular polyps at the base of the stomach

On June 7, 2018, the U.S. Food and Drug Administration required changes to the instructions for omeprazole, pantoprazole, and lansoprazole substituent pump inhibitors and added a warning to the instructions. Omeprazole, pantoprazole, and lansoprazole and other such medications are associated with an increased risk of fundic gland polyps when used for prolonged periods of time, especially for more than one year of use.

To sum up, Helicobacter pylori is a great threat to human beings and is recognized as a class of carcinogens in the world, so the use of omeprazole to kill Helicobacter pylori can largely reduce the risk of us getting stomach cancer.

But it's a drug that's toxic, and omeprazole also increases the risk of polyps in the bottom of the stomach, so be sure to during my time. To the public hospital by the doctor after diagnosis prescribed, and if you need a long time to use the drug patients, be sure to use the drug during the period of more follow-up, more checks, in order to be the first time to find out the side effects of the drug and the appropriate intervention.

Some studies have shown that taking acid-suppressing drugs for a long time has increased the risk of stomach cancer; because our stomach glands secrete gastric acid and various enzymes, which can promote the digestion of food! If you take such drugs for a long time, the glands will atrophy and long term atrophic gastritis will be formed, which is a pre-cancerous lesion, and the probability of cancer will increase, so we don't recommend taking them for a long period of time, usually not more than three months in a single session.

As for whether acid suppressants increase the risk of liver cancer, there have been reports of this. Further research is needed!

Last month I gastroscopy found chronic gastritis with erosion, colorectal chronic inflammatory changes, the hospital hangs a week, after discharge from the hospital and eat omeprazole for two months did not help, when discharged from the hospital the doctor did not say omeprazole can be eaten for a long time, their own online search to learn that can not be eaten for a long time.

After I was discharged from the hospital, I went to the clinic again. The doctor took my pulse and looked at my tongue, and gave me Morodan, Shu Liver and Stomach Pills, and Monkey Head Mushroom Extract Granules, a total of more than five hundred dollars worth of medication, which I have been taking for half a month, and it's still not working. Also after taking Morodan I had abdominal pain and diarrhea, which may be caused by stomach cold. It seems that the doctor didn't see my stomach cold when he took my pulse and looked at my tongue, and gave me cold medicines.

My tongue has thick, white cracked tongue coating. The last time I drank the herbal medicine dispensed by the hospital I also had an increase in abdominal pain, after two days the doctor told me to stop and the herbal packet was taken home to soak my feet.

Also, I have pain in the upper front chest (below the collarbone) and the middle of my back after meals, why is this? What kind of treatment should I take for this?