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Gastric Acid Secretion
Transcript of Gastric Acid Secretion
Food intake leads to reflex secretion of
Deficient levels of glucose in the brain can
also trigger the reflex.
Local gastric and intestinal factors also
influence gastric acid secretion
Chyme in the antrum and duodenum
stimulates the secretion of gastrin. ACh directly - M3 cholinoceptors .
Gastrin - CCKB (gastrin) receptors.
Gastrin activate H (ECL) cells and
secret histamine - H3 receptors.
Hydrogen ions actively secreted into
lumen in exchange for potassium ions.
Process is catalyzed by H+,K+ - ATPase.
HCO3 exchange Cl-Antiporter Cl- diffusion out due to concentration Hydrogen ions actively secreted into
lumen in exchange for potassium ions.
HCO3 exchange Cl- - Antiporter
Cl- diffusion out due to concentration PEPTIC ULCERS A peptic ulcer is a hole in the lining of the stomach or the duodenum of the small intestine. There are two types of peptic ulcers:
A gastric ulcer, which is a peptic ulcer in the stomach.
A duodenal ulcer is a peptic ulcer in the duodenum, the first section of the small intestine.
Peptic ulcers form when the lining of protective mucus and other substances break down, which allows acidic digestive juices to damage the stomach or duodenal lining. Causes of Peptic ulcer:
infection of a type of bacteria called Helicobacter pylori. Other causes of peptic ulcer include
long-term use of nonsteroidal anti-inflammatory drugs (NSAIDS)
after a physically stressful event, such as an illness, surgery or injury
stomach tumor or pancreas tumor
Smoking is a risk factor for developing a peptic ulcer Typical symptoms include epigastric pain, and burning in the upper abdomen.
Other symptoms can include nausea, vomiting, and pain between the shoulder blades in the back.
The pain of a peptic ulcer often begins about two hours after eating and also occurs at night. Eating more food or taking an antacid often decreases or relieves the pain.
Complications of peptic ulcer include the development of a perforated peptic ulcer, which can bleed. Symptoms of a perforated peptic ulcer include blood in the vomit (hematemesis) and black tarry stools (melana). A bleeding perforated peptic ulcer is a life-threatening condition and a medical emergency.
Bleeding from a peptic ulcer can result in anemia. Symptoms of anemia include fatigue, weakness, and light-headedness. Severe bleeding (hemorrhage) can result in shock and death.
If a peptic ulcer gets deep enough to go through the stomach wall, stomach contents may spill into the abdominal cavity, resulting in a serious complication called peritonitis.
Peptic ulcers that have left scars can result in the develoment of a complication called pyloric stenosis. Symptoms of pyloric stenosis include projectile vomiting immediately after a meal. The list of signs and symptoms mentioned in various sources for Peptic Ulcer includes the 6 symptoms listed below:
•Abdominal discomfort - this is the primary symptom; usually chronic and ongoing; the discomfort has particular characteristic patterns:
oAbdominal pain after a meal - usually 2-3 hours later
oAbdominal pain on empty stomach
oAbdominal pain relieved by food
oAbdominal pain relieved by antacids
•Gastrointestinal bleeding - a very serious symptom requiring immediate medical attention; caused by a bleeding ulcers, its symptoms may include:
oBlood in vomit
oVomit with coffee grounds consistency
oBlood in stool
oBlack stool The first step in treating peptic ulcer is prevention.
This includes not smoking.
Nonsteroidal anti-inflammatory drugs (NSAIDS) should be taken only as directed.
Treatment of a peptic ulcer involves reducing the amount of stomach acid so that the lining of the stomach or duodenum can heal.
Medications may include antacids and a proton pump inhibitor, which decrease the production of stomach acid. Drugs called H2 blockers also reduce stomach acid.
Antibiotics may be prescribed when peptic ulcer is caused by a Helicobacter pylori infection.
Treatment of peptic ulcer that leads to bleeding (perforated peptic ulcer) involves hospitalization. Surgery may be required to stop the bleeding and/or to reduce stomach acid production. GASTROESOPHAGEAL REFLUX DISEASE Reflux refers to the stomach acid rising up the "wrong way" back up the esophagus and sometimes into the mouth.
When this occurs chronically it is probably caused by Gastroesophageal Reflux Disease (GERD). •Treatments for gastrointestinal bleeding:
oEmergency treatment - if gastrointestinal bleeding from a bleeding ulcer is suspected
oSee also treatment of anemia - because anemia can result from gastrointestinal bleeding and its blood loss.
•Discontinue causative medications - for NSAIDs and other secondary causes
•Antibiotics - mainly for the treatment of H Pylori infections
•Proton pump inhibitors
•Antacids - these drugs give temporary relief of symptoms of acid secretion but do not solve the problem. (GERD) is usually caused by eating spicy and fatty foods, drinking alcohol and coffee, and certain medications, all of which can lead to relaxation of the lower esophageal sphincter muscle and reflux of stomach acid.
Another risk factor for heartburn is hiatal hernia, in which part of the stomach moves above the diaphragm.
Gastroesophageal reflux is a common condition that often occurs without symptoms after meals. In some people, the reflux is related to a problem with the lower esophageal sphincter, a band of muscle fibers that usually closes off the esophagus from the stomach. If this sphincter doesn't close properly, food and liquid can move backward into the esophagus and may cause the symptoms Persistent heartburn - twice a week or more; most common GERD symptom, though surprisingly you can have GERD without heartburn
Bitter taste in mouth
Increased by bending, stooping, lying down, or eating
Relieved by antacids TREATMENT PROTON PUMP INHIBITOR Since their introduction in the late 1980s, proton pump inhibitors have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers.
improved treatment of various acid-peptic disorders
minimal side effects and few significant drug interactions Recommendations
Although H2 blockers are less expensive than PPIs, PPIs provide superior acid suppression, healing rates and symptom relief.
Therefore, PPIs may be more cost-effective than H2 blockers, especially in patients with more severe acid-peptic disorders, because of their lower and less frequent dosing requirements and their comparatively shorter duration of required therapy.
When deciding which PPI to use, physicians should consider the patient's age, medications, and diagnosis, as well as the expense of therapy.
All five PPIs appear to have similar efficacy in the treatment of various acid-peptic disorders.
The newer agents, rabeprazole and pantoprazole, seem to have fewer drug interactions. This is a particularly important consideration in older patients who are already taking several other medications. While the average wholesale prices of all agents in this class are similar, pantoprazole is the least expensive.
Some controversy remains regarding the need to endoscopically evaluate patients before prescribing PPIs. It would be prudent to consider endoscopic evaluation before initiating PPI therapy in patients 45 years or older and in those with atypical symptoms because pre-endoscopy treatment with a PPI could mask gastric cancer. While some authorities recommend that the H. pylori status of all patients requiring long-term PPI therapy be determined and that those who are positive for H. pylori receive appropriate treatment to eradicate the infection, the FDA's gastrointestinal drug advisory committee has issued assurances regarding the absence of the risk of atrophic gastritis and gastric carcinoma in these patients. Esomeprazole may have increased bioavailability when compared with omeprazole, but otherwise it appears to be similar; omeprazole will soon be available in generic form. Basic Pharmacology
PPIs are substituted benzimidazoles and are generally administered as enteric-coated tablets or capsules that pass through the stomach intact and are absorbed in the proximal small bowel.
Once absorbed, all PPIs have a relatively short plasma half-life (about one to two hours).
Duration of action is much longer because of their unique mechanism of action.
PPIs are lipophilic weak bases that cross the parietal cell membrane and enter the acidic parietal cell canaliculus.
In this acidic environment, the PPI becomes protonated, producing the activated sulphenamide form of the drug that binds covalently with the H+/K+ ATPase enzyme that results in irreversible inhibition of acid secretion by the proton pump.The parietal cell must then produce new proton pumps or activate resting pumps to resume its acid secretion.
In contrast to the other PPIs, rabeprazole forms a partially reversible bond with the proton pump and is activated at a broader range of gastric pH. Therefore, it may have a more sustained acid-suppressing effect than the other PPIs. Side Effects and Precautions
PPIs are generally well tolerated.
The frequency of adverse effects associated with PPIs is less than 5 percent.
The most common adverse effects are headache, diarrhea, abdominal pain, and nausea.
Except for diarrhea, the adverse effects of PPIs do not appear to be related to age, dosage, or duration of treatment.
The diarrhea seems to be related to the profound acid suppression, which has been shown to alter the bacterial content of the gut.
PPIs are only contraindicated if the patient has a known history of hypersensitivity to them, and they should be used with caution in patients with severe hepatic disease.
PPIs cause significant increases in gastric pH, which may alter the absorption of weak acids or bases.
They may inhibit the absorption of drugs such as griseofulvin, ketoconazole, itraconazole, iron salts, vitamin B12, cefpodoxime, and enoxacin, many of which are weak bases and require acid for absorption.
Coadministration with these agents should be approached cautiously because it may result in clinical treatment failure.
PPIs are metabolized to varying degrees by the hepatic cytochrome P450 enzymatic system and may alter drug metabolism by induction or inhibition of the cytochrome P enzymes.
This is an important consideration in patients taking medications with a narrow therapeutic window, such as diazepam, phenytoin, and warfarin. Omeprazole has the greatest potential for altering cytochrome P activity; the other PPIs are less likely to cause clinically significant drug interactions with these agents. PPIs in Acid-Peptic Diseases
GASTROESOPHAGEAL REFLUX DISEASE
Gastroesophageal reflux disease (GERD) can be diagnosed on the basis of the history alone in patients presenting with typical symptoms of heartburn, regurgitation, or both, especially after meals. These symptoms may be exacerbated by recumbency or bending, and relieved by antacids.
It is appropriate to empirically treat patients with classic GERD symptoms with lifestyle modification and patient-directed antacid or acid suppression therapy.PPIs are extremely effective acid suppressants, and it is likely that patients with GERD will respond to them. Physicians generally may assume that patients with typical symptoms who respond to PPI therapy have GERD.
There are two common approaches, but neither has been proved superior.
Step-up therapy starts with over-the-counter or standard-dosage H2 blockers and titrates to symptom control.
Step-down therapy starts with once- or twice-daily PPI therapy and decreases the dosage or changes to the lowest form of acid suppression that will control the patient's symptoms.
In considering which approach would be best for a patient, the physician should consider that PPIs have been shown to be more effective and quicker to eliminate symptoms and heal esophagitis than H2 blockers.
Regardless of treatment, certain patients with long-term symptoms are at increased risk for the development of Barrett's esophagus. There is no evidence that acid suppression therapy with PPIs causes regression of Barrett's esophagus or prevents progression to adenocarcinoma of the esophagus.Thus, the duration of symptoms, rather than the symptom complex or type of treatment, is a more important consideration in determining the need for an endoscopic evaluation to rule out Barrett's esophagus.While most patients with typical symptoms of GERD responsive to empiric therapy do not require endoscopy, patient whose symptoms do not respond to PPI therapy most likely do not have GERD, and further evaluation of their symptoms is needed. PEPTIC ULCERS
Peptic ulcers usually occur in patients with normal acid secretion and gastroduodenal mucosal defenses disrupted because of Helicobacter pylori infection or therapy with non-steroidal anti-inflammatory drugs (NSAIDs).
Studies of PPIs have demonstrated superior healing rates, shorter healing time, and faster symptom relief than are obtained with H2 blockers in these patients.
PPIs have been shown to heal peptic ulcers that may be refractory even to high-dose H2-receptor blockers, and they also exhibit antimicrobial activity against H. pylori in vitro.
While the mechanism of this antimicrobial activity is unclear, it is probably related to inhibition of the urease enzyme produced by H. pylori. PPIs only suppress H. pylori in vivo, and antibiotics alone are ineffective in eradicating H. pylori.
A combination of adequate acid suppression and antibiotic therapy is necessary for the successful eradication of H. pylori.The recurrence rate of peptic ulcers after one year is less than 10 percent when the combination of a PPI and antibiotics is used for H. pylori eradication.
NSAIDs cause peptic ulcers by inhibiting prostaglandin synthesis and weakening gastroduodenal mucosal defenses. Uncomplicated ulcers usually heal after discontinuation of NSAIDs and treatment with standard dosages of PPIs, H2 blockers, or sucralfate (Carafate). PPIs are the treatment of choice for large or complicated ulcers,and they may also be used for prevention of NSAID–induced ulcers. Omeprazole at a dosage of 20 mg daily has been shown to be better tolerated and associated with a lower relapse rate than misoprostol (Cytotec) at a dosage of 200 mcg twice daily. Omeprazole and misoprostol appear to be equally effective in preventing NSAID–induced ulcers. Dosage and Administration
PPIs are inactivated by exposure to gastric juice and are delivered in delayed-release gelatin capsules containing enteric-coated granules (omeprazole and lansoprazole) or in delayed-release enteric-coated tablets (rabeprazole and pantoprazole).
Omeprazole is supplied in doses of 10, 20, and 40 mg, and lansoprazole is supplied in doses of 15 and 30 mg. Both of these agents should be taken 30 minutes before meals, and their capsules should not be opened, chewed, or crushed, but should be swallowed whole.
Other methods of administering omeprazole, lansoprazole, or esomeprazole have been recommended for patients who are unable to swallow intact capsules. The capsules may be opened and the granules sprinkled over a tablespoon of applesauce, pudding, yogurt, or cottage cheese; the food must be swallowed immediately without stirring, crushing, or chewing. In patients with nasogastric or gastrostomy tubes, the granules in one capsule may be mixed with 40 mL of apple juice and injected through the tube, which should be flushed with additional juice to clear the tube.
Rabeprazole is supplied in one dose of 20 mg, and pantoprazole is supplied in one dose of 40 mg. Both agents must be swallowed whole without crushing, chewing, or splitting. Rabeprazole should be taken after meals, but pantoprazole may be taken without regard to meals. Antacids may be administered concomitantly with all PPIs. Dosage adjustments for PPIs are not necessary in elderly patients or those with renal failure or mild hepatic impairment. Lansoprazole, rabeprazole, and pantoprazole should be used with caution in patients with severe hepatic impairment.
The FDA has not approved pantoprazole for maintenance therapy because safety has not been established beyond 16 weeks. At this time, pantoprazole is indicated by the FDA only for the treatment of erosive esophagitis in a dosage of 40 mg daily for eight to 16 weeks. It is the only PPI available for intravenous administration and has recently been approved by the FDA for the short-term intravenous treatment (seven to 10 days) of GERD in hospital inpatients who are unable to take an oral PPI. The intravenous dosage is the same as the oral dosage (40 mg) and should be administered slowly over two to 15 minutes.
Esomeprazole is the s-isomer of omeprazole. It is more bioavailable than omeprazole as the result of a lesser first-pass effect and slower plasma clearance. Esomeprazole in dosages of 20 and 40 mg produces higher 24-hour intragastric pH levels than omeprazole, thus possibly resulting in superior acid control. The incidence and types of adverse effects appear to be similar to those of omeprazole.
Esomeprazole is supplied as delayed-release capsules containing enteric-coated pellets and is available in doses of 20 and 40 mg. It should be taken one hour before meals, and dosage adjustment is not necessary in elderly patients or those with mild to moderate hepatic impairment. Daily dosages should not exceed 20 mg in patients with severe hepatic impairment.
Esomeprazole is indicated for the short-term (four to eight weeks) treatment and healing of erosive esophagitis. If needed, an additional four to eight weeks of therapy may be considered. It is also indicated for maintenance therapy of erosive esophagitis; however, studies do not extend beyond six months of use. Esomeprazole, used as part of triple therapy, is indicated for the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence. Each part of the digestive tube performs at least some of these tasks, and different regions of the tube have unique and important specializations. •Secretion: Delivery of enzymes, mucus, ions and the like into the lumen, and hormones into blood.
•Absorption: Transport of water, ions and nutrients from the lumen, across the epithelium and into blood.
•Motility: Contractions of smooth muscle in the wall of the tube that crush, mix and propel its contents.