Treatment - Pharma lecture



Peptic ulcerHelicobacter pylori, previously?Campylobacter pylori, is a?gram negative,?HYPERLINK "" \o "Microaerophile"microaerophilic?bacterium?found usually in the?stomach. It is present in a person with chronic?gastritis?and?gastric ulcers, conditions not previously believed to have a?microbial?cause. It is also linked to the development of?duodenal?ulcers and?stomach cancer. However, over 80% of individuals infected with the bacterium are?asymptomatic (In medicine, a disease is considered?asymptomatic?if a patient is a carrier for a disease or infection but experiences no symptoms.)Peptic ulcer disease?refers to painful sores or ulcers in the lining of the?stomach?or first part of the small intestine, called the duodenum.. The following are the causes of peptic ulcer:Use of painkillers called nonsteroidal anti-inflammatory drugs (NSAIDs), such as?aspirin,?naproxen?(Aleve,?HYPERLINK ""Anaprox,?HYPERLINK ""Naprosyn, and others),?ibuprofen?(Motrin,?Advil, some types of?Midol, and others), and many others available by prescription; even safety-coated aspirin and aspirin in powered form can frequently cause ulcers.Excess acid production from gastrinomas, tumors of the acid producing cells of the stomach that increases acid output (seen in Zollinger-Ellison syndrome)Excessive drinking of alcoholSmoking?or chewing?tobaccoSerious illnessRadiation?treatment to the area.Signs and symptoms of a peptic ulcer can include one or more of the following:abdominal pain, classically?HYPERLINK "" \o "Epigastric"epigastric?strongly correlated to mealtimes. In case of duodenal ulcers the pain appears about three hours after taking a meal;bloating?and abdominal fullness;waterbrash?(rush of saliva after an episode of regurgitation to dilute the acid in esophagus - although this is more associated with?HYPERLINK "" \o "Gastroesophageal reflux disease"gastroesophageal reflux disease);nausea, and copious vomiting;loss of appetite?and weight loss;hematemesis?(vomiting of blood); this can occur due to bleeding directly from a gastric ulcer, or from damage to the esophagus from severe/continuing vomiting.melena?(tarry, foul-smelling feces due to presence of?oxidized?iron from?hemoglobin).Causes:H. pyloriA major causative factor (60% of gastric and up to 50–75%[17]?of duodenal ulcers) is chronic?inflammation?due to?Helicobacter pylori?that?colonizes?the?HYPERLINK "" \o "Pyloric antrum"antral?mucosa.[18]?The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active?gastritis?(type B gastritis).?HYPERLINK "" \o "Gastrin"Gastrin?stimulates the production of?gastric acid?by parietal cells. In?H. pylori?colonization responses to increased gastrin, the increase in acid can contribute to the erosion of the?mucosa?and therefore ulcer formation.NSAIDsAnother major cause is the use of?NSAIDs, such as?ibuprofen?and?aspirin.[19]?The gastric mucosa protects itself from?gastric acid?with a layer of mucus, the secretion of which is stimulated by certain?prostaglandins. NSAIDs block the function of?HYPERLINK "" \o "Cyclooxygenase"cyclooxygenase?1 (cox-1), which is essential for the production of these prostaglandins. COX-2 selective anti-inflammatories (such as?HYPERLINK "" \o "Celecoxib"celecoxib?or the since withdrawn?HYPERLINK "" \o "Rofecoxib"rofecoxib) preferentially inhibit?cox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration.StressStress due to serious health problems such as those requiring treatment in an intensive care unit is well described as a cause of peptic ulcers, which are termed?stress ulcers.[5]While chronic life stress was once believed to be the main cause of ulcers, this is no longer the case.[20]?It is, however, still occasionally believed to play a role.[20]?This may be by increasing the risk in those with other causes such as?H. pylori?or NSAID use.[21]DietDietary?factors such as?spice?consumption, were hypothesized to cause ulcers until late in the 20th century, but have been shown to be of relatively minor importance.[22]?Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, appear to have little effect.[23][24]?Similarly, while studies have found that alcohol consumption increases risk when associated with?H. pylori?infection, it does not seem to independently increase risk. Even when coupled with?H. pylori?infection, the increase is modest in comparison to the primary risk factor.[25][26][nb 1]OtherAlthough some studies have found correlations between smoking and ulcer formation,HYPERLINK "" \l "cite_note-28"[27]?others have been more specific in exploring the risks involved and have found that smoking by itself may not be much of a risk factor unless associated with?H. pylori?infection. DiagnosisThe diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate.More specifically, peptic ulcers erode the?HYPERLINK "" \o "Muscularis mucosae"muscularis mucosae, at least to the level of the submucosa (contrast with erosions, which do not involve the muscularis mucosae. Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast?x-rays. The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such as?weight loss, because?stomach cancer?can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce?acid. An?HYPERLINK "" \o "Esophagogastroduodenoscopy"esophagogastroduodenoscopy?(EGD), a form of?endoscopy, also known as a?HYPERLINK "" \o "Gastroscopy"gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.One of the reasons that?blood tests?are not reliable for accurate peptic ulcer diagnosis on their own is their inability to differentiate between past exposure to the bacteria and current infection. Additionally, a false negative result is possible with a blood test if the patient has recently been taking certain drugs, such as?antibiotics?or?proton-pump inhibitors. The diagnosis of?Helicobacter pylori?can be made by:Urea breath test?(noninvasive and does not require EGD);Direct culture from an EGD biopsy specimen; this is difficult to do, and can be expensive. Most labs are not set up to perform?H. pylori?cultures;Direct detection of?HYPERLINK "" \o "Urease"urease?activity in a biopsy specimen by?rapid urease test;Measurement of?antibody?levels in the blood (does not require EGD). It is still somewhat controversial whether a positive antibody without EGD is enough to warrant eradication therapy;Stool?antigen?test;Histological examination and staining of an EGD biopsy.The breath test uses radioactive?carbon?to detect H. pylori. To perform this exam the patient will be asked to drink a tasteless liquid which contains the carbon as part of the substance that the bacteria breaks down. After an hour, the patient will be asked to blow into a bag that is sealed. If the patient is infected with H. pylori, the breath sample will contain radioactive?carbon dioxide. This test provides the advantage of being able to monitor the response to treatment used to kill the bacteria.TreatmentYounger patients with ulcer-like symptoms are often treated with?antacids?or?H2 antagonists?before?endoscopy?is undertaken.People who are taking?HYPERLINK "" \o "NSAIDs"nonsteroidal anti-inflammatories?(NSAIDs) may also be prescribed a?prostaglandin?analogue?(HYPERLINK "" \o "Misoprostol"misoprostol) in order to help prevent peptic ulcers. Misoprostol is used for the prevention of?NSAID-induced gastric ulcers. It acts upon gastric?parietal cells, inhibiting the secretion of?gastric acid?by?G-protein coupled receptor-mediated inhibition of?HYPERLINK "" \o "Adenylate cyclase"adenylate cyclase, which leads to decreased intracellular?cyclic AMP?levels and decreased?proton pump?activity at the?apical?surface of the parietal cell. Because other classes of drugs, especially?H2-receptor antagonists?and?proton pump inhibitors, are more effective for the treatment of acute peptic ulcers, misoprostol is only indicated for use by people who are both taking NSAIDs and are at high risk for NSAID-induced ulcers, including the elderly and people with ulcer complications. Misoprostol is sometimes coprescribed with NSAIDs to prevent their common adverse effect of?gastric ulceration?(e.g. with?HYPERLINK "" \o "Diclofenac"diclofenac?in?HYPERLINK "" \o "Arthrotec"Arthrotec).Acid reducing medication.H2 antagonists?or?proton-pump inhibitors?decrease the amount of acid in the stomach, helping with healing of ulcers. H. pyloriWhen?H. pylori?infection is present, the most effective treatments are combinations of 2 antibiotics (e.g.?HYPERLINK "" \o "Clarithromycin"clarithromycin,?amoxicillin,?tetracycline,?HYPERLINK "" \o "Metronidazole"metronidazole) and a?proton-pump inhibitor?(PPI), sometimes together with a bismuth compound. In complicated, treatment-resistant cases, 3 antibiotics (e.g. amoxicillin + clarithromycin + metronidazole) may be used together with a PPI and sometimes with bismuth compound. An effective first-line therapy for uncomplicated cases would be amoxicillin + metronidazole +?HYPERLINK "" \o "Pantoprazole"pantoprazole?(a PPI). SurgeryPerforated peptic ulcer is a surgical emergency and requires surgical repair of the perforation. Most bleeding ulcers require endoscopy urgently to stop bleeding with cautery, injection, or?clipping.Gastric Ulcer: Gastric ulcerPathologyTypeBacterial?infectionCause(s)Heliobacter pylori?bacteriaSymptomsLocalized?stomach?pain?which worsens when eating, anorexia, lack of appetite, weight loss, blood in stool, sour taste in mouth.Mortality RateLowTreatmentsAntibiotics,?Proton pump inhibitors.A?gastric ulcer?is a disintegration of the?stomach?lining which interferes with the production of the?mucous?that coats the lining allowing?stomach acid?to come in contact with the stomach. This causes pain to the patient after eating, which encourages the production of stomach acid. Given time, the acid can eat right through the lining, exposing the?capillaries?beneath, leading to a?bleeding?gastric ulcer, which increases the pain. If left unattended, the ulcer can become perforated, leading to?peritonitis?and?sepsis, either of which is life threatening. ................
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