Katherine Vogel Anderson, PharmD, BCACP

• Associate Professor
• Colleges of Pharmacy and Medicine University of Florida

Within the mucosa is (outermost to innermost): muscularis mucosae weight loss pills for over 50 buy 60mg xenical with mastercard, lamina propria weight loss shots generic 120mg xenical, and epithelium weight loss pills 70 buy line xenical. The mechanisms for each are altered significantly in the diseased state and there are multiple modalities for evaluating these alterations weight loss pills top 10 purchase 60mg xenical visa. The celiac plexus can be blocked via different approaches weight loss 8 week program purchase xenical 120mg with visa, including: transcrural weight loss pills 1995 generic xenical 60mg, intraoperative, endoscopic ultrasound-guided, and peritoneal lavage. Pain management strategies that use regional anesthetic techniques and avoid the use of systemic opioids help reduce the incidence of postoperative nausea and vomiting. The chapter then transitions into a discussion of perioperative considerations for the anesthetist, including the effects of various anesthetic medications and surgical conditions on bowel function and physiology. Its main functions are motility, digestion, absorption, excretion, and circulation. In the second part the specific anatomy and function of the esophagus, stomach, small bowel, and large bowel are discussed. Within the mucosa is (outermost to innermost) the muscularis mucosae, lamina propria, and epithelium. The serosa is a smooth membrane of thin connective tissue and cells that secrete serous fluid that serves to enclose the cavity and reduce friction between muscle movements. The longitudinal muscle layer contracts in order to shorten the length of the intestinal segment whereas the circular muscle layer contracts to decrease the diameter of the intestinal lumen. Between these smooth muscle layers is the myenteric (Auerbach) plexus, which regulates the gut smooth muscle. This is composed of the extrinsic nervous system, which has sympathetic and parasympathetic components, and the enteric nervous system. They travel to the sympathetic chain of ganglia and synapse with postganglionic neurons. Parasympathetic preganglionic fibers originate in the medulla and sacral region of the spinal cord. Vagus nerve fibers innervate the esophagus, stomach, pancreas, small intestine, and the first half of the large intestine. Pelvic nerve fibers innervate the second half of the large intestine, sigmoid, rectal, and anal regions. Two plexuses constitute the enteric nervous system: the myenteric (Auerbach) plexus and the submucosal (Meissner) plexus. Sympathetic stimulation is inhibitory so it will increase the tone of the intestinal wall whereas parasympathetic stimulation is excitatory and will induce intestinal contractions and movement. For example, when there is sympathetic stimulation the tone of the wall increases, the sphincters contract, and, reflexively, the amount of excitatory acetylcholine released is reduced. The mechanism is via -2 activation, which inhibits the release of acetylcholine and through activation which contracts sphincter muscles and relaxes intestinal muscles. The cervical esophagus is approximately 4 to 5 cm long and is surrounded by the trachea anteriorly, the vertebral column posteriorly, and the carotid sheaths and thyroid gland laterally. The thoracic esophagus spans from the suprasternal notch to the diaphragmatic hiatus and lies posterior to the trachea. At the level of the carina, it deviates right to allow room for the aortic arch and runs posteriorly and underneath the left mainstem bronchus. From T8 to the diaphragmatic hiatus (T10) the esophagus runs anterior to the aorta. The abdominal esophagus extends from the diaphragmatic hiatus to the cardia of the stomach. The upper one-third of the esophagus is composed of striated muscle and the remaining two-thirds is smooth muscle. The proximal stomach is the reservoir for undigested food and produces smooth, tonic contractions. The distal stomach grinds, mixes, and sieves food particles via high-amplitude contractions. Notable cell types in the stomach that aid in digestion are the mucous cells, which protect against harsh hydrochloric acid; parietal cells, which secrete hydrochloric acid; chief cells, which secrete pepsin; and G cells, which secrete gastrin. Breaks down food into chyme through physical and chemical mechanisms Chemically digests chyme for absorption in the small intestine Absorption of nutrients from chyme Further nutrient absorption A space for mixing of chyme with bacteria to form fecal matter Duodenum Jejunum Ileum Cecum Ascending colon Runs superiorly from the cecum to the right inferior Peristaltic waves move the feces superiorly where bacteria border of the liver where it turns 90 degrees to become digest the waste and further nutrients, water, and vitamins the transverse colon are absorbed Crosses abdominal cavity right to left just below the stomach Runs inferiorly along the left side of the abdominal cavity Lower left quadrant of the abdominal cavity Posterior pelvic cavity. Along the anterior surface of the sacrum and coccyx Fecal formation Stores fecal matter prior to elimination. Further absorbs water, nutrients, vitamins Stores fecal matter prior to elimination Stores fecal matter prior to elimination. Distention will activate stretch receptors allowing the internal anal sphincter to relax and allow for defecation. Transverse colon Descending colon Sigmoid colon Rectum the duodenum is the first and smallest section of the small intestine. Its main function is to chemically digest the chyme received from the stomach in preparation for absorption. The pancreas, liver, and gallbladder secrete digestive enzymes through the ampulla of Vater into the middle portion of the duodenum. The digested chyme from the duodenum enters the jejunum where it is mixed and circulated for exposure to the jejunal walls for nutrient absorption. The walls of the jejunum are folded many times over to increase its surface area and allow for maximal absorption of nutrients. By the time chyme enters the ileum, almost 90% of all available nutrients are absorbed. It serves to absorb vitamin B12 and other products of digestion that were not previously absorbed in the jejunum. It ends at the ileocecal valve-a circular muscle that serves to prevent reflux of colonic contents into the small intestine. It contracts in response to colonic dilation and relaxes in response to ileal dilation. Briefly, the cecum is a pouch at the beginning of the large intestine that allows for mixing of the chyme from the small intestine with bacteria to form fecal matter. The ascending colon transports the fecal matter superiorly along the right side up to the transverse colon. The transverse colon, the longest portion of the large intestine, crosses the abdominal cavity. The feces then enter the descending colon, which stores the feces until it is ready for transport, inferiorly and along the left side of the abdominal cavity to the sigmoid colon. Again, the walls of the descending colon allow for further absorption of water and nutrients. The sigmoid colon is an S-shaped, curved region that stores then transports fecal matter from the descending colon to the rectum and anus for elimination. The final portion of the large intestine is the rectum where feces are stored until elimination. This activates stretch receptors and leads to relaxation of the internal anal sphincter allowing for elimination. Emphasis is placed on mechanism, how motility and transit are altered by various disease states, and methods for evaluating motility. Swallowing starts with the oropharynx pushing food backward and downward while the muscles of the nasopharynx prevent food from entering the nasal passages. The epiglottis moves upward in a protective mechanism over the larynx and trachea to prevent aspiration. The act of swallowing inhibits the respiratory center to protect from aspiration but it is so shortlived it is unnoticeable. Afferent nerve fibers transmit to the dorsal vagal complex activating efferent fibers that terminate either on the striated muscle of the esophagus or on the nerves of the enteric nervous system. Etiologies can be grouped into anatomical, mechanical, and neurologic, although many disease states involve overlap between two or all three. Anatomical etiologies include the presence of diverticula, hiatal hernia, and changes associated with chronic acid reflux. These anatomical abnormalities interrupt the normal pathway of food as it travels to the stomach which, in turn, changes many of the pressure zones of the esophagus. There is also a neurologic component to these diseases but the result is the same- the esophagus is unable to relax properly for food travel. In diffuse esophageal spasm the muscle contractions are uncoordinated and, as a result, food does not properly move downward. Neurologic disorders such as stroke, vagotomy, or hormone deficiencies will alter the nerve pathways such that the appropriate sensing and feedback are disrupted. In evaluating esophageal function, it is important to select a study with an appropriate clinical correlation-is it a problem with motility or is it an anatomical abnormality If it is a questionable motility problem, then an esophageal manometry study is best. A special catheter detects changes in pressure in the esophagus at various levels. The catheter is then pulled back into the esophagus and pressure measurements are made at different levels. These evaluate the act of swallowing and visualize the lining of the esophagus for anatomic abnormalities. Before discussing the transit of food through the stomach and small intestine it is important to understand their actions during the fasting state. As described previously, the stomach is a J-shaped sac that serves as a reservoir for large volumes of food, mixes and breaks down food to form chyme, and slows emptying into the small intestine. Solids must be broken down into 1 to 2 mm particles before entering the duodenum, and they take approximately 3 to 4 hours to empty from the stomach. The motility of the stomach is controlled by intrinsic and extrinsic neural regulation. Parasympathetic stimulation to the vagus nerve increases the number and force of contractions whereas sympathetic stimulation inhibits these contractions via the splanchnic nerve. Neurohormonal control is also at play in that gastrin and motilin will increase the strength and frequency of contractions and the gastric inhibitory peptide will inhibit them. Emptying of the stomach is controlled by neural and hormonal mechanisms as well as the composition of ingested food. Duodenal distention decreases the gastric tone to slow emptying, and increased fat content triggers the release of cholecystokinin to further inhibit stomach motility. Drug-induced conditions include the administration of opioids (to be discussed later in the chapter), and the use of vasoactive agents. Vasoactive drugs increase catecholamine concentrations leading to sympathetic stimulation and, therefore, decreased motility. These drugs are often given intraoperatively or to critically ill patients for blood pressure control. Neurologic disorders resulting in decreased gastric motility include vagal neuropathies and gastroparesis. Finally, conditions that are commonly present in severely compromised patients, such as those with hyperglycemia, increased intracranial pressure, and mechanical ventilation can decrease gastric motility. Efforts to increase motility using drugs like erythromycin and metoclopramide have been used with some success. The most prevailing test to evaluate gastric motility is the gastric emptying study. The patient fasts for at least 4 hours prior to the study then consumes a meal with a tightly bound radiotracer, commonly egg albumin. Continuous or frequent imaging occurs for the next 60 to 120 minutes and the measurement of time for 50% of the ingested meal to empty is determined. Small intestinal motility mixes the contents of the stomach with digestive enzymes, further reducing particle size and increasing solubility. However, the major function of the small intestine is to circulate the contents and expose them to the mucosal wall in order to maximize absorption of water, nutrients, and vitamins before entering the large intestine. The circular and longitudinal muscle layers work in a coordinated fashion to achieve segmentation. Segmentation occurs when two nearby areas contract and thereby isolate a segment of intestine. Then a contraction occurs in the middle of that isolated segment, further dividing it. Contractions in the middle of those segments continue to occur and the process ensues. Segmentation allows the contents to remain in the intestine long enough for the essential substances to be absorbed into the circulation. It is controlled mainly by the enteric nervous system with modulation of motility by the extrinsic nervous system. When considering small bowel dysmotility it is helpful to distinguish etiologies based on reversible and nonreversible causes. For reversible causes, mechanical obstruction should be the first to come to mind. In this case, there is a physical obstruction the muscles of the intestine cannot overcome. Although the large intestine is rich with bacteria, the small intestine usually has fewer than 100,000 organisms per milliliter. Disrupting this condition with bacterial overgrowth leads to alterations in absorptive function leading to diarrhea. Other reversible causes include ileus, electrolyte abnormalities, and critical illness. In structural causes there may be abnormalities with the intestinal smooth muscle, in which it cannot produce proper contractions. Short bowel syndrome can be considered a structural etiology in that a large portion of the small intestinal structure is simply not present. In patients who have had a section of their small bowel resected, the remaining portion may not provide sufficient functional compensation, resulting in diarrhea, malnutrition, and weight loss.

Injury to kidneys seldom occurs unless there is preexisting kidney disease weight loss pills lipo 6 cheap xenical 60 mg otc, nephrotoxic injury weight loss 8 week program buy xenical pills in toronto, hypovolemia weight loss pills 2x order xenical on line amex, or a combination thereof weight loss in cats purchase xenical 120mg amex, which will exacerbate renal dysfunction weight loss breakfast ideas generic 120mg xenical with amex. There is experimental evidence that propofol can prevent renal ischemia-reperfusion injury through inhibition of oxidative stress pathways weight loss pills under 30 dollars purchase 60mg xenical otc. The decrease in cardiac output and systemic arterial pressure results in a carotid and aortic baroreceptor-mediated increase in sympathetic nerve tone to the kidney, with renal vasoconstriction, antidiuresis, and anti-natriuresis. The renin-angiotensin-aldosterone system undoubtedly augments the renal responses to positive pressure ventilation. Although earlier studies suggested that hypotensive anesthesia can be well tolerated without permanent impairment of renal function, a more recent retrospective analysis suggests that mean arterial pressures less than 60 mmHg for 11 to 20 min or less than 55 mmHg for more than 10 min are associated with acute kidney injury. Administration of sodium nitroprusside decreases renal vascular resistance but tends to shunt blood flow away from the kidney. Moreover, its administration is associated with marked reninangiotensin activation and catecholamine release, which results in rebound hypertension if the infusion is suddenly discontinued. Sladen for contributing a chapter on this topic in the prior edition of this work. Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension. Vasopressin regulation of sodium transport in the distal nephron and collecting duct. Thirty years of research on atrial natriuretic factor: historical background and emerging concepts. Physiological effects of vasopressin and atrial natriuretic peptide in the collecting duct. The renin-angiotensin-aldosterone system in renal and cardiovascular disease and the effects of its pharmacological blockade. Atrial natriuretic peptide and renal dopamineric system: a positive friendly relationship Dopaminergic control of renal tubular function in patients with compensated cirrhosis. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. Hemodynamic monitoring and management in patients undergoing high risk surgery: a survey among North American and European anesthesiologists. Fluid management during video-assisted thoracoscopic surgery for lung resection: a randomized, controlled trial of effects on urinary output and postoperative renal function. Targeting urine output and 30-day mortality in goal-directed therapy: a systematic review with meta-analysis and meta- regression. Effect of the volume of fluids administered on intraoperative oliguria in laparoscopic bariatric surgery: a randomized controlled trial. Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo. Propofol prevents renal ischemia-reperfusion injury via inhibiting the oxidative stress pathways. The effect of changing from pressure support ventilation to volume control ventilation on renal function. Hypotensive anesthesia for total hip arthroplasty: a study of blood loss and organ function, brain, heart, liver and kidneys. Regional blood flow in dogs during halothane anesthesia and controlled hypotension produced by nitroprusside or nitroglycerin. Effects of fenoldopam on renal blood flow and systemic hemodynamics during isoflurane anesthesia. Effect of nicardipine on renal function following robot-assisted laparoscopic radical prostatectomy in patients with pre-existing renal insufficiency. Challenges in measuring glomerular filtration rate: a clinical laboratory perspective. Comparison of the modification of diet in renal disease and Cockcroft-Gault equations for dosing antimicrobials. Alteration of renal hemodynamics by thiopental, diazepam and ketamine in conscious dogs. For anesthetic drugs, the processes of distribution and elimination (metabolism and excretion) govern this relationship. Estimates of distribution volumes and clearances, pharmacokinetic parameters, are derived from mathematical formulas fit to measured blood or plasma concentrations over time following a known drug dose. Front-end kinetics refer to alterations in cardiac output that substantially influence the pharmacokinetic behavior of anesthetic drugs in terms of onset and duration of effect. Contextsensitive decrement time, which is defined as the time required to reach a certain plasma concentration after a termination of long infusion, characterizes the back-end kinetics. Hysteresis refers to the time delay between changes in plasma concentration and drug effect. Hysteresis accounts for the time required for drug to diffuse from the plasma to the site of action plus the time required, once drug is at the site of action, to elicit a drug effect. In particular, pharmacodynamics describes the relationship between drug concentration and pharmacologic effect. The effect-site concentration describes a mathematically derived virtual location where an anesthetic drug exerts its effect. The concentration range where changes in drug effect occur is known as the dynamic range. Levels below the dynamic range are ineffective and those above the dynamic range do not provide additional effect. Anesthetics rarely consist of one drug, but rather a combination of drugs to achieve desired levels of hypnosis, analgesia, and muscle relaxation. Pharmacokinetic and pharmacodynamic principles characterize the magnitude and time course of drug effect, but because of complex mathematics, they have limited clinical utility. Advances in computer simulation have brought this capability to the point of real-time patient care in the form of drug displays. Some of these include age; body habitus; gender; chronic exposure to opioids, benzodiazepines, or alcohol; presence of heart, lung, kidney, or liver disease; and the extent of blood loss or dehydration. The aim of this chapter is to provide an overview of key principles in clinical pharmacology used to describe anesthetic drug behavior. Pharmacokinetics is the relationship between drug administration and drug concentration at the site of action. The section on pharmacokinetics introduces both the physiologic processes that determine pharmacokinetics and the mathematical models used to relate dose to concentration. Pharmacodynamics is the relationship between drug concentration and pharmacologic effect. In fact, most anesthetics are a combination of several drugs with specific goals in analgesia, sedation, and muscle relaxation. This section reviews common pharmacodynamic interactions and how they influence anesthetic effect. The last section briefly addresses patient demographics and how they influence anesthetic behavior. When formulating an anesthetic, the following factors need to be considered in determining the correct dose: age; body habitus; gender; chronic exposure to opioids, benzodiazepines, or alcohol; presence of heart, lung, kidney, or liver disease; and the extent of blood loss or dehydration. This section focuses on body habitus and age, both known to influence the pharmacology of many anesthetic drugs and both of which serve as excellent examples of altered pharmacokinetics and pharmacodynamics. The group of blue drops emerging from the pipe at the top right represent a bolus dose that, when administered to the tank of water, evenly distributes within the tank. The processes of absorption, distribution, and elimination (metabolism and excretion) govern this relationship. Absorption is not relevant to intravenously administered drugs but is relevant to all other routes of drug delivery. The time course of intravenously administered drugs is a function of distribution volume and clearance. Estimates of distribution volumes and clearances are described by pharmacokinetic parameters. Pharmacokinetic parameters are derived from mathematical formulas fit to measured blood or plasma concentrations over time following a known amount of drug dose. If an injected drug disperses and distributes instantaneously throughout the tank without any drug degradation, the distribution volume is estimated using the simple relationship between dose. Considering the elimination of drug from the tank and the changes If drug elimination occurs as a first-order process. When a drug is administered intravenously, some drug stays in the vascular volume, but most of the drug distributes to peripheral tissues. This distribution is often represented as additional tanks (peripheral distribution volumes) connected to a central tank (blood or plasma volume). For the calculation of distribution volumes, peripheral tissue concentrations are difficult to measure whereas plasma concentrations are easily measured. The peripheral tank represents the drug volume of distribution in peripheral tissues. There may be more than one peripheral tank (volume) to best describe the entire drug disposition in the body. The more soluble a drug is in peripheral tissue relative to blood or plasma, the larger the peripheral volumes of distribution. Thus, the total volume of distribution may even be larger than the two tanks added together. At 2 minutes (left panel) and 4 minutes (right panel) following a 10-mg drug bolus, tank concentrations are decreasing from 5 to 2. Accounting for elimination, estimates of the distribution volume at each time point are both 1 L. For a bolus dose, assume that the volume of distribution is 1 L at time = 0 and that it then increases to 14 L as the plasma concentration falls over the next 10 minutes. The increase of the distribution volume is due to the distribution of drug to peripheral tissue and a decrease in the plasma concentration. For a constant infusion, assume the volume of distribution is again 1 L at time = 0 and that it then increases to 5 L as the plasma concentrations also increase to a steady-state concentration over the next several hours. It is estimated as the sum of the central and peripheral apparent distribution volumes. With additional distribution volumes, the overall volume of distribution can change over time and is a function of how drug is administered as well. For example, consider simulations of concentrations and distribution volumes over time following a bolus dose or a continuous infusion of an intravenous anesthetic Clearance Clearance describes the rate of drug removal from the plasma/blood. Systemic clearance permanently removes drug from the body, either by eliminating the parent molecule or by transforming it into metabolites. Intercompartmental clearance moves drug between plasma and peripheral tissue tanks. By way of clarification, in this chapter, the words compartment and tank are interchangeable. Clearance is defined in units of flow, that is, the volume completely cleared of drug per unit of time. The elimination rate is not an accurate method of describing the mass of drug removed over time. For example, assuming a first-order process, when plasma concentrations are high, the rate of drug elimination is high. The concentration changes for two time windows are labeled with dashed lines from 1 to 2 minutes (time window A) and from 3 to 4 minutes (time window B), respectively. In this simulation, the total amount of drug at each time can be calculated from the known volume of distribution and measured concentration. The concentration change in time window A is larger than in time window B even though they are both 1 minute in duration. They are different, and neither can be used as a parameter to represent a measure of drug removal from the body. For discussion purposes, assume that concentration is the power necessary to push drug out of the water tank. To standardize the elimination rate, the eliminated amount of drug is scaled to concentration. If the time interval is narrowed so that the time window approaches zero, the definition of clearance becomes: dA (t) Clearance = dt C (t) Clearance = 0 dA (t) 0 C (t) dt (18. To illustrate the relationship between clearance and volume of distribution, consider the following simulation using a generic drug dosed in milligrams into a single compartment (tank) representing the distribution volume that has a clearance of 1 L/min. Assume that when drug is administered, the tank is well stirred and has instantaneous mixing throughout the entire volume. Assume the distribution volume is 4 L, the total dose of drug is 64 mg, and that drug elimination is proportional to the amount of drug present inside the tank at any given time. A generic drug dose of 64 mg is administered into a single compartment volume of 4 L that has a clearance of 1 L/min. Drug elimination is proportional to the amount of drug present inside the compartment at any given time, otherwise known as first-order elimination kinetics. At 1-minute intervals, one of the 4 L is cleared along with all drug contained in that liter. With a clearance of 1 L/min, the amount of drug distributed to one fourth of compartment volume (1 L) will be cleared every minute. When assuming instantaneously mixing, the ratio of the amount of drug removed within the cleared portion of the distribution volume to the amount of drug within the total distribution volume will remain the same as illustrated in Eq. According to mass balance, the rate at which drug flows out of metabolic organs is the rate at which drug flows into them minus the metabolic rate. If nearly 100% of the drug is extracted by the liver, this implies that the liver has a very large metabolic capacity for the drug.

Buy generic xenical. New Fat Loss Pill? Hello!.

Syndromes

• Chest pain
• Cap the container. Keep it in the refrigerator or a cool place during the collection period. Label the container with your name, the date, the time of completion, and return it as instructed.
• Restricting fluid intake to a volume equal to the volume of urine produced
• Tube through the nose into the stomach (nasogastric tube) to look for signs of bleeding
• Get plenty of rest and drink fluids.
• Unresponsive reflexes