Good afternoon, my name is Sarah, I am a pharmacy practice resident at VCU . . . I will be speaking about medications related to disorders of the GI tract. This is a very broad category, but we will be following the assigned chapter closely. I will talk more in depth about GERD (acid reflux), than I will about constipation or diarrhea, as determined by the prevalence of these disorders in the American patient population. Please feel free to interrupt me with questions at any time .
We will focus first on the process of acid secretion in the GI tract, most notably the stomach. After we have an understanding of the cellular key players in acid secretion, we will discuss the various medications available and how each works. As this is the topic I would like to focus on today, we will talk about dosages of medications, as well as side effects and their place in treatment. We will also discuss complications of Gird We will then turn our attention to the lower GI tract and discuss the mechanism of motility, disorders of motility, and what treatment options we have for those patients.
We will not be covering all diagnoses of the GI tract that require medication for management. We will focus on the most frequently diagnosed and utilized medications, including GERD/NERD, diarrhea and constipation, and a few miscellaneous items. POINT OUT UPPER GI AND LOWER GI TRACT DEVIATION
Starting with the upper GI tract, there are 2 main categories of disease states related to acid secretion. The first is GERD, which can span a wide range of symptoms and complications. The first, dyspepsia, is also known as heartburn or NERD. This occurs with acid and stomach contents backs into the esophagus without major irritation or erosion of the esophageal lining. Repeated contact with an acidic substance eventually leads to erosion, creating an esophagitis. Esophagitis or inflammation of the stomach lining can lead to a full ulceration in the epithelial lining, which can be associated with a H. pylori bacterial infection. Pts that have H. pylori w/o and ulcer and H. pylori with an ulcer should both be treated, as H. pylori has been identified as a risk factor for forming an ulcer
Gastric acid secretion is a continuous process in which multiple central and peripheral factors contribute to a common endpoint, secretion of hydrogen ions by parietal cells. Neuronal (acetylcholine), paracrine (histamine), and endocrine (gastrin) factors all regulate acid secretion. Receptors for Ach, histamine and gastrin are on the basolateral membrane of parietal cells in the body and fundus of the stomach. Ach: stimulates gastic acid secretion via response to sight, smell, taste, or anticipation of food. It also increases the release of histamine from the enterochromaffin-like (ECL) cells in the fundus of the stomach, and of gastrin in the gastric antrum. Histamine: ECL cells are close to parietal cells, histamine is released and diffuses to parietal cells, activating histamine receptors. Gastrin: most potent inducer of acid secretion. CNS activation, distention of stomach, and gastric contents stimulate gastrin release. Gastrin induces ECL cells to release histamine, and also (to a lesser extent), stimulates direct acid secretion.
Point out fundus, antrum, and LES
Defense mechanisms are required to protect the esophagus and stomach from the extremely high concentration of hydrogen ions LES: prevents the reflux of contents into the esophagus-talk about this causing dyspepsia, certain foods trigger relaxation of the LES Stimulated by prostaglandin E2 and I2, soluble gastric mucus is secreted and forms an insoluble gel on the mucosal surface of the stomach ASA, alcohol, and other drugs that inhibit prostaglandin secretion inhibit the secretion of this protective mucus Superficial gastric epithelial cells secrete bicarbonate ions, which neutralize the acid in the stomach, raising pH, and therefore preventing acid-mediated damage.
The demonstrate reflux by determining pH level in esophagus
Of the 20-40% of patients that experience heartburn, 30-80% of those patients will have esophagitis.
Simethicone is an anti-foaming agent that decreases the surface tension of gas bubbles , causing them to combine into larger bubbles in the stomach that can be passed more easily by burping
Notice that the aluminum containing antacid can neutralize 3 hydrochloric acid molecules at a time. There is also no carbon dioxide production Notice the calcium containing product forms carbon dioxide, this is what gives antacids the belching and gas sensation associated with them
Excessive use of antacids coupled with impaired renal function can cause electrolyte imbalances. This can lead to high calcium concentrations, which can lead to kidney stones or calcium calcification in other areas of the body (heart). Increases in Al concentration leads to aluminum toxicity. Will talk about acid-rebound phenomenon at the end, as all acid suppressants can cause this.
Incidence of GERD can label a patient with asthma as ‘exacerbation-prone’ due to the ensuing inflammation associated with acid reflux. Acidic irritation of the esophageal epithelium leads to a metaplastic change from a normal squamous type epithelium to an intestinal-type, columnar lining (Barrett’s)
3 Drug combo: protonix 40 bid + clarithromycin 500mg BID + amoxicillin 1 gram Bid OR metronidazole 500mg BID)
Fluid content is the principal determinant of stool volume and consistency Water accounts for 70-85% of stool weight The daily challenge for the gut is to extract water, minerals, and nutrients from the luminal contents, leaving enough liquid for proper expulsion of waste material via defecation. 2 types of movement: Propulsive: giant migrating contractions, propagate over extended lengths, evoke mass transfer of feces Non-propulsive (mixing) 8-9 liters of water enter the small bowel, 1-1.5 liters cross into the colon, but only 100mL of water is expelled via feces. 6
Causes of constipation: Lack of dietary fiber Drugs Hormonal disturbances Neurogenic disorders
Metamucil: 2.5-4 grams per dose (1-3 teaspoonfuls in 250mL juice), now in tablet form Methylcelluose and polycarbophil: 4-6 grams per day
Bisacodyl: enteric coated tabs-takes 6 hours to work suppository for rectal administration, work within 30-60 minutes **should not be used for more than 10 days to avoid developing an atonic nonfunctioning colon Castor oil: the triglyceride is hydrolyzed in the small bowel by lipases into glycerol and ricinoleic acid (active), which stimulates the secretion of fluid and electrolytes and speeds transit time seldom recommended due to palatibility recommended dose: 15-60 mL for adults Senna: produce giant migrating colonic contractions and induce water and electrolyte secretion. laxative effect noted 6-12 hours after administration due to requiring activation in the colon
DISCUSS ADVERSE EFFECTS Just like the antacids that contain Mg, accumulation of Mg and Phos can be symptomatic, even deadly in elderly patients with poor renal function Liquid: Magnesium hydroxide 400 mg/5 mL: 5-15 mL as needed up to 4 times/day
ADVERSE EFFECTS WITH MINERAL OIL: ASPIRATION PNA
If diarrhea is occuring due to an infectious cause, must treat the underlying infection with antibiotics Most diarrhea is self-limiting, 72 hours in duration
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