Proton pump inhibitors (PPIs) may reduce the benefits of aspirin in patients with coronary artery disease (CAD)

Proton pump inhibitors (PPIs) may reduce the benefits of aspirin in patients with coronary artery disease (CAD), researchers from Denmark report.

Previous research has suggested that concomitant PPI use might be responsible for the reduced aspirin efficacy seen in some patients.

“Aspirin is the mainstay of secondary antithrombotic treatment; accordingly, low-dose aspirin lowers the risk of vascular events by 32% in high-risk patients,” explain Anne-Mette Hvas (Aarhus University Hospital, Brendstrupgaardsvej) and colleagues in the journal Heart.

“However, platelet response to aspirin is variable and in some patients platelet aggregation is inhibited less than expected and these patients might be at an increased risk of cardiovascular events.”

PPIs exert their antacid effect by inhibiting an ATPase associated with gastric parietal cells and raising intragastric pH, which can greatly reduce the lipophilicity of aspirin and, therefore, potentially its efficacy.

To better understand the effects of PPIs on aspirin function, the investigators studied 418 patients with stable CAD, all of whom were taking aspirin 75 mg/day and 54 of whom were also taking PPIs.

Analysis revealed that platelet aggregation was significantly greater in patients taking aspirin as well as a PPI (180 units/min) than in those taking aspirin only (152 units/min).

Platelet activation, as assessed by levels of soluble serum P-selectin, was also significantly increased in those taking both aspirin and a PPI (88.5 ng/ml) than those taking aspirin only (75.4 ng/ml).

Importantly, these differences were not explained by differences in age, sex, body mass index, blood pressure, family history of ischemic heart disease, smoking, or diabetes, all of which factors were well balanced between patient groups.

Although the authors did not demonstrate a causal link between PPI use and reduced aspirin function, “these findings may nevertheless affect the clinical practice of antithrombotic treatment,” conclude the researchers.

“In view of the widespread use of PPIs, a randomised double-blind crossover study is needed to explore further the inhibitory effect of PPIs on aspirin,” the investigators recommend.

What is the treatment for acid reflux?

Diet

The vast majority of people with acid reflux will get better if they make some changes to their diet. Some foods are safe for heartburn sufferers, while others are major triggers of it.

It would be easy to say that there is a reflux diet. Unfortunately, we all react differently to different foods.

Below is a list of foods/drinks that commonly cause irritation and/or heartburn:

• Alcohol
• Black pepper
• Chili and chili powder
• Citrus fruit, pineapple
• Coffee
• Garlic
• Spicy food
• Tea
• Tomatoes, tomato sauce, tomato juice, ketchup
• Vinegar
• Some patients with acid reflux say these gassy foods cause discomfort:
• Beans
• Broccoli
• Brussel Sprouts
• Cabbage
• Cauliflower
• Kale
• Fizzy drinks (sodas)
• Medications

Acid suppressant - these have been shown to be effective, such as histamine2-receptor antagonists (blockers). Histamines are good at reducing inflammation. An inflamed stomach produces more acid - blocking this extra production of acid helps prevent the acids from building up and seeping upwards.

Propton pump inhibitors - these reduce the production of acid in the stomach. They act on cells in the stomach wall and produce stomach acids.

Prokinetic agents - these promote the emptying of the stomach, stopping it from becoming overfull.

Antiacids - commonly used to treat mild acid-related symptoms, such as heartburn or indigestion. They neutralize the acids in the stomach. These are not recommended for frequent heartburn for patients with GERD.

What are the symptoms of acid reflux?, What causes acid reflux?

What are the symptoms of acid reflux?

Asthma - gastric juices seep upwards into the throat, mouth and air passages of the lungs

Chest pain - part of the heartburn sensation

Dental erosion

Dysphagia - difficulty swallowing

Heartburn - a burning feeling rising from the stomach or lower chest towards the neck

Hoarseness

Regurgitation - bringing food back up into the mouth

What causes acid reflux?

Acid reflux commonly occurs when the lower esophageal sphincter (LES) does not work properly, and allows acid to seep upwards from the stomach to the esophagus. Although we know that a faulty LES is a common cause, we are not sure why it becomes faulty. One of many reasons could be that pressure in the stomach rises higher than the LES can withstand.

Here are some common causes of acid reflux:

Pregnancy - more commonly found during the third trimester of a pregnancy. As the growing baby presses on the stomach, contents may back up into the esophagus. Doctors say antacids will not relieve acid reflux caused by pregnancy. Patients find that if they eat smaller meals but eat more meals per day, it helps. In the vast majority of cases the acid reflux will disappear soon after the baby is born.

Large meals and eating habits - people who have large meals will usually find that their acid reflux will improve if they cut down portion sizes. Patients who kept a food diary, noting down everything they ate and linking certain foods to incidences of acid reflux, have experienced a reduction in acid reflux.

Bending forward - this movement will not usually cause acid reflux unless there is another underlying trigger or problem.

Hiatus hernia (hiatal hernia) - a condition where the upper part of the stomach protrudes into the chest through a small opening in the diaphragm. Hiatal hernias are commonly caused by severe coughing, vomiting, straining, sudden physical exertion, pregnancy, and obesity.

Peptic ulcers and insufficient digestive enzymes - peptic ulcers and not enough digestive enzymes in the stomach may slow down the digestive process, causing an accumulation of gastric acids that back up into the esophagus.

Asthma - experts still argue about which came first, the asthma or the acid reflux - did the asthma cause the acid reflux or did the acid reflux cause the asthma? Nobody has a definite answer to the relationship between asthma and acid reflux. Some say that the coughing and sneezing brought on by asthmatic attacks can cause changes in the chest which trigger acid reflux. Others blame asthma medications - they are taken to dilate the airways, but might also relax the esophageal sphincter.

Most asthma sufferers say that their asthma is worsened by acid reflux because the acid that seeps into the esophagus from the stomach stimulates the nerves along the neck into the chest, causing bronchial constriction and breathing problems.

Smoking - research has shown that the saliva of smokers contain lower levels of bicarbonates, which neutralize acids. Cigarette smoking also reduces the production of saliva. Smoking also stimulates the production of stomach acid, weakens the esophageal sphincter, promotes the movement of bile salts from the intestine to the stomach (making the acids more harmful), and slows down digestion (making stomach pressure last longer because it takes more time to empty).

Alcohol - patients have commented that quitting alcohol, or cutting down consumption significantly improved their symptoms.

Complications of indigestion

In the vast majority of cases indigestion is mild and does not happen frequently. Severe indigestion can occasionally cause the following complications:

Esophageal stricture - if the indigestion is caused by acid reflux, when stomach acids leak back up into the esophagus and irritate the mucosa, the esophagus can become scarred. The esophagus can eventually become narrow and constricted. Patients with esophageal stricture may have swallowing difficulties; food can get stuck in the throat, causing chest pain. Surgery is sometimes needed to widen the esophagus.

Pyloric stenosis - this is caused by long-term irritation of the lining of the digestive system from stomach acid. The Pylorus - the passage between the stomach and the small intestine - becomes scarred and narrowed. Food is not properly digested. Surgery may be required to widen the pylorus.

Peritonitis - inflammation of the peritoneum (the tissue layer of cells lining the inner wall of the abdomen and pelvis). Surgery can repair damage to the peritoneum, and antibiotics are sometimes prescribed to deal with infection.

Treatment options for indigestion - Proton Pump Inhibitors

Treatment for indigestion depends on what is causing it and how severe symptoms are.

Diet and lifestyle changes - if symptoms are mild and your indigestion is not occurring often, some lifestyle changes will probably ease symptoms. This usually involves consuming less fatty foods, less caffeine, alcohol and chocolates, sleeping at least 7 hours every night, and avoiding spicy foods.

Medications:

Antacids - examples include Alka-Seltzer, Maalox, Rolaids, Riopan, and Mylanta. These are OTC (over-the-counter, no prescription needed) medicines. These are usually the first medications doctors recommend.

H-2-receptor antagonists - examples include Zantac, Tagamet, Pepcid and Axid. Some of these are OTC while others are prescription drugs. They reduce levels of stomach acids and last longer than antacids. However, antacids are effective faster. Some patients may experience nausea, vomiting, constipation, diarrhea, and headaches. Other side-effects may include bruising or bleeding.

PPIs (proton pump inhibitors) - examples include Aciphex, Nexium, Prevacid, Prilosec, Protonix and Zegerid. PPIs are very effective for patients who also have GERD (gastroesophageal reflux disease). They reduce stomach acid and are stronger than H-2-receptor antagonists. Side effects may include cough, headache, dizziness, back pain, abdominal pain, wind, nausea and/or vomiting, constipation and diarrhea. In very rare cases long-term use can lead to bone fractures.

Prokinetics - an example includes Reglan. This medication is helpful if the stomach empties slowly. Side effects may include tiredness, depression, sleepiness, anxiety and muscle spasms.

Antibiotics - if Helicobacter pylori is causing peptic ulcers which result in indigestion an antibiotic will be prescribed. Side effects may include upset stomach, diarrhea and fungal infections.

Antidepressants - if no causes for indigestion are found after a thorough evaluation and the patient has not responded to treatments, the doctor may prescribe antidepressants. Antidepressants sometimes ease the discomfort by reducing the patient's sensation of pain. Side effects may include nausea, headaches, agitation, constipation, and night sweats.

The doctor may also recommend making changes to the patient's current medication if it is thought that it could be contributing to the indigestion. Sometimes aspirin or ibuprofen may be discontinued and alternative medications sought. It is important to change medications under the supervision of your doctor, and not to do this on your own.

How to diagnose indigestion? - Proton Pump Inhibitors

For the majority of patients indigestion is mild and does not occur very often. In such cases no treatment from a doctor is required. People who experience indigestion regularly should see their GP (general practitioner, primary care physician). You should also see your doctor if you experience severe discomfort or pain.

A doctor will ask the patient about symptoms, his/her medical and possibly family history, and examine the chest and stomach. This may involve pressing different areas of the abdomen to find out whether any are sensitive or tender.

Blood test - if the patient has any symptoms of anemia the doctor may order a blood test.

Endoscopy - patients who have not responded to treatment, or those with certain signs and symptoms, may be advised to have their abdomen examined in more detail. An endoscopy takes place in hospital. A long thin tube with a camera at the end - an endoscope - goes through the patient's throat and into the stomach. The surgeon can see images of the inside of the abdomen on an external monitor.

Tests to diagnose Helicobacter pylori infection - this may include a urea breath test, a stool antigen test, and a blood test. Peptic ulcers are often cause by this bacterium.

Liver function test - if the doctor thinks the patient may have a biliary condition, which affects the bile ducts in the liver. This involves a blood test that determines how the liver is working.

X-rays - usually an upper-gastrointestinal and small bowel series. X-rays are taken of the esophagus, stomach and small intestine.

Abdominal ultrasound - high-frequency sound waves make images that show movement, structure and blood flow. A gel is applied to the patient's abdomen and a hand-held device is pressed against the skin. The device emits sound waves and the doctor can see the insides of the abdomen in detail on a monitor.

Abdominal CT (computed tomography) scan - this may involve injecting a dye into the patient's veins. The dye shows up on the monitor. The CT scan takes a series of X-ray images to produce a 3-dimensional image of the inside of the abdomen.

Causes of indigestion - Proton Pump Inhibitors

Indigestion is usually related to lifestyle and what we eat and drink. It may also be caused by infection or some other digestive conditions. Some common causes include:

• Eating too much
• Eating too rapidly
• Consuming fatty or greasy foods
• Consuming spicy foods
• Consuming too much caffeine
• Consuming too much alcohol
• Consuming too much chocolate
• Consuming too many fizzy drinks
• Emotional trauma
• Gallstones
• Gastritis (inflammation of the stomach)
• Hiatus hernia
• Infection, especially with bacteria known as Helicobacter pylori
• Nervousness
• Obesity - caused by more pressure inside the abdomen
• Pancreatitis (inflammation of the pancreas)
• Peptic ulcers
• Smoking
• Some medications, such as antibiotics and NSAIDs (non-steroidal anti-inflammatory drugs)
• Stomach cancer

When a doctor cannot find a cause for indigestion the patient may have functional dyspepsia - a type of indigestion that may undermine the stomach's ability to accept and digest food and then pass that food on to the small intestine.

Symptoms of indigestion - Proton Pump Inhibitors

Most people with indigestion feel pain and discomfort in the stomach or chest area. The sensation generally appears soon after consuming food or drink. In some cases symptoms may appear some time after a meal. Some people feel full during a meal, even if they have not eaten much.

Heartburn and indigestion are two separate conditions. Heartburn is a burning feeling behind the breastbone, usually after eating.

The following symptoms are also common:

• Nausea
• Belching
• Feeling bloated (very full)
• In very rare cases indigestion may be a symptom of stomach cancer.

Mild indigestion is rarely anything to worry about. You should see your doctor if symptoms continue for more than two weeks. See your doctor immediately if pain is severe, and the following also occur:

• Loss of appetite or weight loss
• Vomiting
• Black stools
• Jaundice (yellow coloring of eyes and skin)
• Chest pain when your exert yourself
• Shortness of breath
• Sweating
• Chest pain radiation to the jaw, arm or neck

Dyspepsia, indigestion and upset stomach are the same terms

Dyspepsia, also known as indigestion or upset stomach, is a term that describes discomfort or pain in the upper abdomen. It is not a disease. Dyspepsia is a group of symptoms which often include bloating, nausea and burping.

Indigestion is usually caused by stomach acid coming into contact with the mucosa of the digestive system - the sensitive protective lining of the digestive system. Stomach acids break down the mucosa, causing irritation and inflammation, which trigger the symptoms of indigestion.

In the majority of cases indigestion is linked to eating and/or drinking. Sometimes it may be caused by infection or some medications.

Drug interactions and Over-dosage of Rabeprazole

Drug interactions

Rabeprazole decreases the concentration of ketoconazole in the plasma (in 33%), increases the concentration of digoxin (in 22%), and does not interact with liquid antacids. Rabeprazole is compatible with any medicine metabolized by the CYP450 (theophylline, warfarin, diazepam, phenytoin).

Over-dosage

There is no available data on symptoms of rabeprazole overdose.

Contraindications, Restriction of usage and Side effects of Rabeprazole

Contraindications: hypersensitivity to rabeprazole, substituted benzimidazoles or any of components of its pharmaceutical forms.

pregnancy: FDA Pregnancy Ratings: B

lactation: Thomson Lactation Ratings: Infant risk cannot be ruled out.

Restriction of usage: acute hepatic failure

pediatric use in patients under 18 years of age (there are insufficient data about safety and efficiency of rabeprazole in this group of patients)

Side effects:

Rabeprazole adverse reactions/side effects include

• In clinical trials the most common side effect assessed as possibly or probably related to AcipHex was headache in 2.4% of patients vs 1.6% taking placebo.
• diarrhea
• vomiting
• nausea
• abdominal pains
• constipation
• meteorism
• dry mouth
• increased or decreased appetite
• asthenia
• headache
• anxiety
• sleeplessness
• vertigo
• thrombocytopenia
• granulocytopenia
• leukocytopenia
• skin eruption
• erythema
• myalgia
• arthralgia
• muscle or bone pain

Indications and usage of Rabeprazole

Short-term treatment in healing and symptomatic relief of duodenal ulcers and erosive or ulcerative gastroesophageal reflux disease (GERD); maintaining healing and reducing relapse rates of heartburn symptoms in patients with GERD; treatment of daytime and nighttime heartburn and other symptoms associated with GERD; long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and in combination with amoxicillin and clarithromycin to eradicate Helicobacter pylori.

1. Gastric ulcer
2. Peptic ulcer disease (PUD)
3. Maintenance of healing of erosive or ulcerative GERD
4. Healing of erosive and ulcerative GERD
5. Healing of duodenal ulcers.
6. Treatment of symptomatic GERD
7. Treatment of pathological hypersecretory conditions (Zollinger-Ellison syndrome)
8. Helicobacter pylori eradication to reduce risk of duodenal ulcer recurrence

What is Rabeprazole?

Rabeprazole is an antiulcer drug in the class of proton pump inhibitors.

Rabeprazole is used in

1. Short-term treatment in healing and symptomatic relief of duodenal ulcers and erosive or ulcerative gastroesophageal reflux disease (GERD).
2. maintaining healing and reducing relapse rates of heartburn symptoms in patients with GERD.
3. treatment of daytime and nighttime heartburn and other symptoms associated with GERD.
4. long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and in combination with amoxicillin and clarithromycin to eradicate Helicobacter pylori.

Pharmacology of Pantoprazole

Pantoprazole is metabolized in the liver by the cytochrome P450 system. Metabolism mainly consists of demethylation by CYP2C19 followed by sulfation.

Another metabolic pathway is oxidation by CYP3A4. Pantoprazole metabolites are not thought to have any pharmacological significance.

Pantoprazole is relatively free of drug interactions, however it may alter the absorption of other medications that depend on the amount of acid in the stomach, such as ketoconazole or digoxin.

What is Pantoprazole?

Pantoprazole is a proton pump inhibitor drug used for short-term treatment of erosion and ulceration of the esophagus caused by gastroesophageal reflux disease.

Initial treatment is generally of eight weeks' duration, after which another eight week course of treatment may be considered if necessary. It can be used as a maintenance therapy for long term use after initial response is obtained.

This medication may affect the results of certain lab tests, such as drug screenings (pantoprazole can cause a false positive for THC). It is recommended you make sure laboratory personnel and your doctor know you are using this drug.