Therapy of gastrointestinal ulcers
Hemorrhage is the leading cause of death associated with peptic ulcer disease. Lifetime risk of bleeding for those without treatment is approximately 35 . Spontaneous, and often temporary, cessation of bleeding occurs in about 70 of patients. EGD is appropriate in the acute setting. This is successful in identifying the cause of bleeding in the majority of cases. Sometimes bleeding can be controlled with thermal coagulation via a heater probe. Stigmata of recent bleeding include the presence of an adherent clot or the presence of a visible vessel in the ulcer base. In general, approximately 30 of those with stigmata of recent bleeding will rebleed and a large proportion of these will require emergent operation. Operative strategy is that of duodenotomy with oversewing of the bleeder combined with a definitive acid-reducing procedure. Operative intervention is necessary when there is ongoing massive hemorrhage leading to shock or cardiovascular instability, prolonged blood loss...
Bleeding from a peptic ulcer remains the most common source of upper GI bleed accounting for greater than 50 . This can be controlled approximately 94 of the time using endoscopic techniques. Visualization of an ulcer itself can be an important predictor of rebleed. Ulcers have four recognized appearances clean base a flat, pigmented spot, which at times may be purple an adherent clot a visible vessel or active bleeding. These are all considered to have an increased risk of hemorrhage. A clean ulcer base rarely bleeds a flat pigmented base will bleed in about 10 of patients an adherant nonbleeding clot rebleeds in about 20 of patients and a visible vessel carries about a 40-80 rebleed rate.
While most cases of acromegaly are not inherited, mutations in the GNAS1 gene can cause GH-secreting pituitary adenomas (somatotrophinomas). These can be transmitted in an autosomal dominant pattern. Familial acromegaly may also be a feature of multiple endocrine neoplasia type I (MEN I), an autosomal dominant disorder that includes peptic ulcer disease and pituitary, parathyroid, and pancreas endocrine abnormalities.
Patients have abdominal- pain radiating to tlic back, nausea and vomiting that does not relieve the pain, leukocytosis, and elevated amylase lipase, Perforated peptic ulcer disease also may have elevated amylase and presents similarly, but patients have free air on abdominal x-ray and history of peptic ulcer disease,
With short-term use, glucocorticoids are practically free of adverse effects, even at the highest dosage. Long-term use is likely to cause changes mimicking the signs of Cushing's syndrome (endogenous overproduction of cortisol). Sequelae of the anti-inflammatory action lowered resistance to infection, delayed wound healing, impaired healing of peptic ulcers. Sequelae of exaggerated glucocor-ticoid action a) increased gluconeogen-esis and release of glucose insulin-dependent conversion of glucose to triglycerides (adiposity mainly noticeable in the face, neck, and trunk) steroid-diabetes if insulin release is insufficient b) increased protein catabolism with atrophy of skeletal musculature (thin extremities), osteoporosis, growth retardation in infants, skin atrophy. Sequelae of the intrinsically weak, but now manifest, mineralocorticoid action of cortisol salt and fluid retention, hypertension, edema KCl loss with danger of hypokalemia.
Dried rhizomes and roots of a legume, Glycyrrhiza glabra, distributed from Europe to western Asia and North Africa, are the source of licorice, used to flavor tobacco and confectionery. In India, licorice is chewed with betel nut. Medicinally, it has been valued against indigestion. Derivatives of licorice have been used to treat stomach ulcers. Spanish (including Italian and Greek) licorice is considered the best quality. Lower quality Oriental licorice is cultivated in the Middle East, the Caucasus, and north China. In the United States, roots from different regions are blended to make various brands of licorice extract.
After 10 days, the life in shelters became very stressful for many victims. An increase of acute stress responses, including serious stress peptic ulcer, was reported. The Department of Internal Medicine of Kobe University Medical School was busy with the treatment of many cases of extremely serious bleeding ulcers. Anxiety reactions and sleep disorders were common 6 . An increased occurrence of pneumonia and bronchitis was reported among the elderly (the earthquake took place in January, which was wintertime in Japan).
Many patients are asymptomatic. Early symptoms are polyuria (large amounts of urine), anorexia, and constipation, as well as weakness, fatigue, drowsiness, and lethargy. As the hypercalcemia increases, abdominal pain (from peptic ulcer disease), nausea, and vomiting are typical. The patient may report generalized bone pain and may have had recent fractures from what appeared to be little cause.
In the area of a gastric or duodenal peptic ulcer, the mucosa has been attacked by digestive juices to such an extent as to expose the subjacent connective tissue layer (submucosa). This self-digestion occurs when the equilibrium between the corrosive hydrochloric acid and acid-neutralizing mucus, which forms a protective cover on the mucosal surface, is shifted in favor of hydrochloric acid. Mucosal damage can be promoted by Helicobacter pylori bacteria that colonize the gastric mucus.
Risk factors that may have contributed to the bleeding include and nonsteroidal anti-inflammatory drugs, anticoagulants, colonic diverticulitis, renal failure, coagulopathy, colonic polyps, and hemorrhoids. Patients may have a prior history of hemorrhoids, diverticulosis, inflammatory bowel disease, peptic ulcer, gastritis, cirrhosis, or esophageal varices.
Most common in children, who have 25100 red-brown macules or barely elevated papules, usually over the trunk lesion becomes a wheal when rubbed (Darier's sign) solitary mastocytoma usually appears within first month of life rubbery, yellow to brown, plaques, urticate with or without vesiculation after rubbing (bullous urticaria pigmentosa) telangiectasia macu-laris eruptiva perstans brown macules and telangiectasias with erythema, often over upper trunk associated with peptic ulcer disease diffuse mastocytosis bullae in infancy, replaced by doughy skin, with generalized pruritus dermatographism, bullae after minor skin trauma mast cell infiltration of liver, spleen, skeleton, and gastrointestinal tract flushing syndrome, most common in early life
Additional Side Effects CV Vasodilation, pallor. Oral Dry mouth, stomatitis. GI GI pain, peptic ulcers, nausea, dyspepsia, flatulence, GI fullness, excessive thirst, GI bleeding (higher risk in geriatric clients), perforation. CNS Headache, nervousness, abnormal thinking, depression, euphoria. Hypersensitivity Bronchospasm, anaphylaxis. Miscellaneous Purpura, asthma, abnormal vision, abnormal liver function.
Peptic ulcer disease refers to ulcerative disorders in the lower esophagus, upper duodenum, and lower portion of the stomach. Approxiamtely 4 to 5 million people in the United States 710 Peptic Ulcer Disease have peptic ulcers, which are sharply circumscribed breaks of the mucosa that may extend through the tissue layers of the muscle and serosa into the abdominal cavity. The types of peptic ulcers are gastric and duodenal, both of which are chronic diseases. Stress ulcers, which are caused by a physiological response to major trauma, are clinically distinct from chronic peptic ulcers. Gastric ulcers are less common than duodenal ulcers and usually occur in the lesser curvature of the stomach within 1 inch of the pylorus. The ulcer formation is caused by an inability of the mucosa to protect itself from damage by acid pepsin in the lumen (which is caused by a breakdown of the defensive factors). Duodenal ulcers occur in the proximal part of the duodenum (95 ), are less than 1 cm in...
Complications caused by pernicious anemia include macrocytic anemia and gastrointestinal disorders. Pernicious anemia impairs myelin formation and thus alters the structure and disrupts the function of the peripheral nerves, spinal cord, and brain. Patients have a high incidence of benign gastric polyps, peptic ulcers, and gastric carcinoma. Low hemoglobin levels and consequent hypoxemia of long duration can result in congestive heart failure and angina pectoris in the elderly. If it is left untreated, pernicious anemia can cause psychotic behavior or even death.
Contraindications Severe hypotension, hemorrhage, arterial bleeding, liver dysfunction, peptic ulcer. Use of the extended-release tablets and capsules in children. Special Concerns Extended-release niacin may be hepatotoxic. Use with caution in diabetics, gall Side Effects GI N&V, diarrhea, peptic ulcer activation, abdominal pain. Dermatologic Flushing, warm feeling, skin rash, pruritus, dry skin, itching and tingling feeling, keratosis nigricans. Other Hypotension, headache, macular cystoid edema, amblyopia. NOTE Megadoses are accompanied by serious toxicity including the symptoms listed in the preceding as well as liver damage, hyperglycemia, hyperuricemia, arrhythmias, tachycardia, and dermatoses.
Long before the mechanisms of activation of acid secretion by the stomach were recognized, extract of belladonna was found to ameliorate peptic ulcer symptoms. However, the active ingredient, atropine, has a generalized effect on all the muscarinic receptors in the body, resulting in side effects, such as blurred vision, dry mouth, and urinary tract dysfunction that resulted in abstinence from the drug. Even though atropine was later replaced by more selective M1 receptor antagonists (e.g., pirenzepine), the general muscarinic side effects, although reduced compared with atropine remained.19
Aspartic proteinases may play many roles in human disease, although in many cases the speculations outnumber the proofs. For many years, gastric pepsin was suspected of contributing to the formation of stomach ulcers. In cases of cancer of the esophagus, pepsinogen secretion is stimulated and the excessive amounts of pepsin that result could play a role in extensive degradation of the esophagus and upper stomach (Varis et al., 1991).
Helicobacter pylori is a gram-negative microaerophilic spiral bacterium that predominantly inhabits the antral region of the human stomach. While H. pylori can also be found in the body or fundus of the stomach or in gastric metaplasia of the duodenum, it seems well adapted only to gastric tissues. It is not found, for instance, in normal small or large intestine or esophagus. In vitro, it grows quite slowly and only under conditions of reduced (but not absent) oxygen. In the absence of relatively complex antimicrobial treatment protocols, this bacterium can apparently establish a life-long infection. The organism resides within the mucus layer of both surface and glandular epithelium. This ecologic niche serves to protect the organism from both the harsh environmental conditions of the stomach as well as from host-effector mechanisms. However, despite the fact that host responses are ineffective in clearing the organism, H. pylori induces a state of active chronic gastric...
When the tetanus bacteria enter an open wound, they multiply and produce a potent neurotoxin called tetanospasmin, which enters the bloodstream and acts on the spinal ganglia and central nervous system by interfering with the function of the postsynaptic inhibitory potentials. The anterior horn cells become overstimulated, thus resulting in excessive muscle contraction. Toxins may also act directly on skeletal muscle and cause muscle contraction. Complications include lung disorders such as pneumonia, pulmonary emboli, atelectasis, cardiac dysrhythmias, gastric ulcers, and flexion contractures. Tetanus results in approximately 5 deaths per year in the United States death usually results from autonomic dysfunction such as extremes in blood pressure, cardiac dysrhythmia, or cardiac arrest.
The a- and -stereoisomers of 18-glycyrrhetinic acid acid FW 470.7) and carbenoxolone (3-hydroxy-11-oxoolean-12-en-30-oicacid 3-hemisuccinate disodium salt FW 614.7) are available from Sigma Chemical. The structure-activity relationships for glycyrrhetinic acid derivatives are illustrated in Fig. 1. In addition to their actions on gap junctions, licorice and its analogs have been shown to interact with mineralocorticoid receptors and to inhibit the enzyme 11-dehydrogenase (53-55), resembling symptoms caused by excess mineralocorticoid secretion (i.e., pseudo-aldosteronism). These side effects have led to use of carbenoxolone in trials for the treatment of gastric ulcer (56). Carbenoxolone has also been shown to shift the reversal potential of the opioid current in locus coeruleus neurons to the K+ equilibrium potential.
Surgery, radiotherapy, and chemotherapy are the major treatment modalities for pancreatic cancer. A distal pancreatectomy, used more often with islet cell tumors than with exocrine cancer, removes only the tail of the pancreas or the tail and part of the body. The spleen is also removed. A total pancreatectomy or a pancreatoduodenectomy (Whipple procedure) is used when cure is the objective. In a total pancreatectomy, the entire pancreas and spleen are removed. The Whip-ple procedure involves removal of the head of the pancreas, distal stomach, gallbladder, pancreas, spleen, duodenum, proximal jejunum, and regional lymph nodes. The procedure induces exocrine insufficiency and insulin-dependent diabetes. A pancreatojejunostomy, hepaticoje-junostomy, and gastrojejunostomy are performed with the Whipple procedure to reconstruct the gastrointestinal (GI) system. A vagotomy is usually done in both procedures to decrease the risk of peptic ulcer.
The efficiency of eradication of H. pylori infection (around 95-98 ) and the use of antibiotics have completely changed the approach to peptic ulcer therapy, significantly reducing the use of antisecretory compounds. Nonetheless, as shown in Table 1, antiulcer drugs represent the second most frequently sold drug class.
Peptic Ulcer A peptic ulcer is a hole or a break in the mucous membrane that lines the digestive tract, allowing digestive acids to come in contact with cells in the lining, injuring them. Peptic ulcers most often occur in the first few inches of the duodenum (duodenal ulcers) or in the stomach (gastric, or stomach, ulcers). While stomach ulcers occur more frequently in women than in men and generally develop after age 60, duodenal ulcers are the most common type of ulcer among both men and women and usually first occur between ages 30 and 50. Many people who have a peptic ulcer have no symptoms, but most experience a burning or gnawing pain in the abdomen. Pain caused by a duodenal ulcer tends to follow a consistent pattern pain is absent on awakening, appears by midmorning, is relieved by eating, recurs 2 to 3 hours after each meal, and wakes the person during the night. This pattern continues for a week or more, but the pain may disappear without treatment and then recur months or...
Cholecystitis, peptic ulcer disease, or hepatitis can cause nausea and vomiting and should be excluded. Gastroenteritis, appendicitis, pyelonephritis, and pancreatitis also should be excluded. Obstetric explanations for nausea and vomiting may include multiple pregnancies or a hydatidiform mole.
The term 'acute abdomen' defines a clinical syndrome characterized by a history of hitherto undiagnosed abdominal pain lasting less than one week. A large number of disorders, ranging from benign, self-limited diseases to conditions that require immediate surgery, can cause acute abdominal pain. Eight conditions account for over 90 of patients who are referred to hospital and are seen on surgical wards with acute abdominal pain acute appendicitis, acute cholecystitis, small bowel obstruction, urinary colic, perforated peptic ulcer, acute pancreatitis, acute diverticular disease, and non-specific, non-surgical abdominal pain ('dyspepsia', 'constipation').
There was certainly no quantitative way of relating chemical properties to the biological properties. I began to wonder whether this pharmaceutical research could ever be as exciting again as I had found the research during my PhD years. Meanwhile SK&F moved out of London to Welwyn Garden City and then underwent an internal reorganization that brought in several scientists from ICI Pharmaceuticals. In particular James Black came in like a breath of fresh air to head Pharmacology and I instantly knew that here was somebody with whom I wanted to collaborate. Black initiated several lines of research but eventually all work was concentrated (because of limited resources) on to the search for compounds to block a new type of histamine receptor, the putative H2 receptor. This was a novel approach to controlling the secretion of gastric acid the therapeutic aim was to treat peptic ulcer disease. This was a real challenge for the medicinal chemists because there was no chemical lead other...
Contraindications Hemorrhagic tendencies (including hemophilia), clients with frail or weakened blood vessels, blood dyscrasias, ulcerative lesions of the GI tract (including peptic ulcer), diverticulitis, colitis, SBE, threatened abortion, recent operations on the eye, brain, or spinal cord, regional anesthesia and lumbar block, vitamin K deficiency, leukemia with bleeding tendencies, thrombocytopenic purpura, open wounds or ulcerations, acute nephritis, impaired hepatic or renal function, or severe hypertension. Hepatic and renal dysfunction. In the presence of drainage tubes in any orifice. Alcoholism. Special Concerns Use with caution in menstruation, in pregnant women (because they may cause hypoprothrombinemia in the infant), during lactation, during the postpar-tum period, and following cerebrovas-cular accidents. Geriatric clients may be more susceptible to the effects of anticoagulants.
Always biopsy any gastric ulcer to exclude malignancy (duodenal ulcers do not have to be biopsied initially). 3. The major complication is perforation. Look for peritoneal signs, history of peptic ulcer disease, or free-air on abdominal x-ray. Treat with antibiotics and laparotomy with repair of perforation
Visceral pain is not felt in the internal organ where it originates, but is rather referred to a cutaneous zone (of Head) specific to that organ. This phenomenon is explained by the arrival of sensory impulses from both the internal organ and its related zone of Head at the posterior horn at the same level of the spinal cord the brain thus (mis)interprets the visceral pain as originating in the related cutaneous zone. The pain may be described as burning, pulling, pressure, or soreness, and there may be cutaneous hyperesthesia to light touch. Certain etiologies (e.g., angina pectoris, cholecystitis, gastric ulcer, intestinal disease) can produce ipsilateral my-driasis. In addition to the zones of Head, referred pain may also be felt in muscles and connective tissue (pressure points, as in Blumberg's sign or McBurney's point). Physicians should beware of
Gastrointestinal Increased gastric acidity leads to peptic ulcer, nausea and vomiting. Central nervous system (CNS) Agitation, restlessness, tremors, seizures. Metabolic Reduced serum K and Ca (chronic osteoporosis 2 cups day, 100 mg day). Muscle Increased contractility, high creatine phosphokinse (CPK), rhabdomyolysis.
Action Kinetics Atropine blocks the action of acetylcholine on post-ganglionic cholinergic receptors in smooth muscle, cardiac muscle, exocrine glands, urinary bladder, and the AV and SA nodes in the heart. Ophthalmologically, atropine blocks the effect of acetylcholine on the sphincter muscle of the iris and the accommodative muscle of the ciliary body. This results in dilation of the pupil (mydriasis) and paralysis of the muscles required to accommodate for close vision (cycloplegia). Peak effect Mydriasis, 30-40 min cycloplegia, 1-3 hr. Recovery Up to 12 days. Duration, PO 4-6 hr. tV2 2.5 hr. Metabolized by the liver although 30 -50 is excreted through the kidneys unchanged. Uses PO Adjunct in peptic ulcer treatment. Irritable bowel syndrome. Adjunct in treatment of spastic disorders of the biliary tract. Urologic disorders, urinary incontinence. During anesthesia to control salivation and bronchial secretions. Has been used for parkinsonism but more effective drugs are available.
Gastric pH should be mainained at 5.0 with antacids, H2 blockers, or proton pump inhibitors. This usually does not stop ongoing bleeding but is necessary to limit progression of disease and allow for healing. Endoscopic electrocautery or epi-nephrine injection may be attempted with bleeding ulcers or gastritis. Sclerotherapy or endoscopic banding may be attempted with variceal bleeding. Angiographic em-bolization does not work well because of the rich submucosal vascular plexus of the stomach. Selective infusion of vasopressin into the left gastric artery may lead to a temporary response.
Eradication of Helicobacter pylori C. This microorganism plays an important role in the pathogenesis of chronic gastritis and peptic ulcer disease. The combination of antibacterial drugs and omeprazole has proven effective. In case of intolerance to amoxicillin (p. 270) or clarithromycin (p. 276), metronidazole (p. 274) can be used as a substitute. Colloidal bismuth compounds are also effective however, the problem of heavy-metal exposure compromises their long-term use.
The pathophysiology of peptic ulcers, whether gastric or duodenal, is multifac-torial. Ulcers develop depending on the balance of injurious factors and host defense mechanisms. Environmental stressors are numerous. Acid secretion is involved in the final common pathway of ulcer formation. In regards to duodenal ulceration, mucosal exposure of acid is a necessary component of their pathogenesis. In general, patients with duodenal ulcers have an increased capacity for acid secretion. Maximal acid output in normal patients is usually around 20 mEq hour but patients with duodenal ulcers may exceed 40 mEq hr. There is, however, variability in this finding to the extent that some patients with duodenal ulcers have maximal acid outputs that are considered in the normal range. Additionally, patients with duodenal ulcer have increased basal acid outputs with normal basal gastrin levels. The role that acid secretion plays with the formation of gastric ulcers is less clear. Hypersecretion of...
Helicobacter pylori is a spiral bacterium which specifically colonizes gastric mucosa. It is able to survive in a near neutral pH through the production of urease. H. pylori infection has been correlated with the formation of peptic ulcers. Several lines of evidence link H. pylori to peptic ulceration. Additionally, the prevalence of H. pylori in patients with duodenal ulceration is near 100 . Patients with gastric ulcers have a prevalence of H. pylori in the range of 60-80 . Comparatively, Helicobacter colonizes approximately 20 of those without peptic ulcer disease. Consequently, the evaluation for and the treatment of Helicobacter infection is an integral part of the treatment of peptic ulcer disease. There are several other environmental factors which are associated with the development of peptic ulcers. Cigarette smoking has been associated with peptic ulcer disease in so far as it impairs healing, decreases the effectiveness of therapy, increases recurrence rates, and increases...
The antimicrobial treatment of Helicobacter pylori is an important component of the treatment of peptic ulceration. As previously mentioned, H. pylori is associated with duodenal ulceration in nearly 100 of cases and with gastric ulceration in about 60 of cases. Helicobacter infection should be considered when patients experience ulcer recurrence on maintenance medical therapy or when peptic ulcers fail to heal. Multiple medical regimens exist consisting of some combination of clarithromycin, metronidazole, bismuth, and or tetracycline. Triple therapy is becoming more popular with use of a PPI and two antibiotics (i.e., omeprazole, clarithromycin and metrinidazole). Regardless of the exact regimen used, a 10-14 day course leads to eradication of H. pylori in approximately 90 of cases.
In simplest terms, there are three basic operations for uncomplicated peptic ulceration parietal cell vagotomy, truncal vagotomy with pyloroplasty, and truncal vagotomy with antrectomy. With the advent of H2 receptor antagonists and, more recently, proton pump inhibitors the surgical treatment of peptic ulcer disease has become less common. Surgical treatment is indicated when ulcers fail to heal after 3 months of appropriate medical therapy or when ulcers recur on maintenance therapy. Surgery is also indicated when malignancy cannot be excluded and when complications of disease occur. Complications of peptic ulcer disease include perforation, hemorrhage, and obstruction.
The first H2 receptor antagonist developed was burimamide, followed by metiamide. With minimal structural alterations, Brimblecombe etal.3 developed cimetidine, the first 1 billion a year blockbuster drug (see 8.03 Medicinal Chemistry as a Scientific Discipline in Industry and Academia Personal Reflections). The modification of the chemical structure of cimetidine, with elimination of the imidazole ring, led to ranitidine, the pharmacokinetic characteristics of which provided improved patient compliance. These drugs provided effective inhibition of production and release of gastric acid via a pharmacologically proven mechanism, and became the gold standard therapy for peptic ulcers during the 1980s, leading to a marked improvement in the quality of life for a large number of patients, and substantial reductions in the societal costs of the treatment and incapacitation associated with gastric ulceration. These shortcomings were overcome with the discovery and development of proton pump...
Contraindications Hypotension, hypertension, CAD, coronary occlusion, AV conduction defects, vasomotor instability, pronounced brady-cardia, peptic ulcer, asthma (latent or active), hyperthyroidism, parkin-sonism, epilepsy, obstruction of the bladder, if the strength or integrity of the GI or bladder wall is questionable, peritonitis, GI spastic disease, inflammatory lesions of the GI tract, marked vagotonia. Not to be used IM or IV.