By P. Treslott. Colby-Sawyer College.

Also inhibited is C-fiber sensory nerve activation asthma symptoms that is unresponsive to standard ther- in animal models trusted 300 mg lopid, which may in turn suppress reflex- apy cheap 300mg lopid fast delivery. A provocative factor such as prolonged allergen exposure or a respiratory infection Clinical Uses often precedes status asthmaticus buy lopid 300 mg visa. A rapid increase in Cromolyn sodium and nedocromil sodium are used al- the daily use of bronchodilators to control acute symp- most exclusively for the prophylactic treatment of mild toms is a danger sign of an impending crisis lopid 300 mg on line. Treatment to moderate asthma and should not be used for the con- includes oxygen cheap lopid 300 mg fast delivery, inhaled short-acting 2-agonists, and trol of acute bronchospasm. Subcutaneous - in about 60 to 70% of children and adolescents with agonists can be given to those who respond poorly to in- asthma. The underlying pathophysiology of asthma is best (C) Status asthmaticus is best treated with inhaled described by which of the following statements? The standard treatment regimen for asthma is best ceptor agonists or inhaled corticosteroids are not described by which of the following? Because of extensive systemic (C) Inhaled corticosteroids only side effects, oral corticosteroids are not typically (D) A combination of inhaled bronchodilators and used to treat asthma except when symptoms cannot inhaled corticosteroids be controlled by standard therapy. Dysphonia, candidiasis, and sore throat are associ- (A) Tachycardia, dizziness, and nervousness ated with the use of inhaled corticosteroids. The (B) Dysphonia, candidiasis, and sore throat emergence of Churg-Strauss syndrome, though un- (C) Dyspepsia and Churg-Strauss syndrome common, is associated with the use of oral (D) Nausea, agitation, and convulsions leukotriene modulators. Theophylline produces a (E) Muscle tremor, tachycardia, and palpitations range of side effects, including nausea, agitation, and life-threatening convulsions. No credible data indicate either SUPPLEMENTAL READING that asthma is psychosomatic or that it develops in Bisgaard H. Long-acting inhaled beta2- cated for the treatment of status asthmaticus, as agonist therapy in asthma. Medical and ventila- status asthmaticus, as does increased use of inhaled tory management of status asthmaticus. Department of Health adrenoceptor agonists are used as bronchodilators and Human Services, Public Health Service, as needed to relieve acute symptoms. As asthma is National Institutes of Health, National Heart, Lung an inflammatory disease of the airway, inhaled corti- and Blood Institute, 1997. Although the signs are alarming to the of warfarin, and elevated warfarin levels can cause patient, the intern on duty does not view them as bleeding. Warfarin levels should be patient has been taking warfarin for atrial fibrilla- monitored in this patient, and his warfarin dosages tion. About 3 weeks ago the asthma symp- farin completely or administering vitamin K is not toms were increasing in frequency and severity, necessary, as the bleeding complications are not se- prompting his pulmonologist to prescribe oral theo- vere. Moreover, these actions could precipitate ad- phylline on top of the inhaled corticosteroid and - verse clotting events (e. Seibert DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Alosetron 473 Loperamide 473 Apomorphine 476 Mesalamine 480 Bisacodyl 476 Metoclopramide 472 Bismuth subsalicylate 473 Misoprostol 481 Budesonide 481 Nizatidine 479 Cascara 475 Octreotide 482 Cimetidine 479 Olsalazine sodium 480 Cisapride 472 Omeprazole 479 Diphenoxylate 473 Ondansetron 477 Docusate 474 Pantoprazole 479 Erythromycin 472 Phenolphthalein 475 Esomeprazole 479 Polyethylene glycol 475 Famotidine 479 Prochlorperazine 477 Granisetron 477 Promethazine 477 Infliximab 481 Rabeprazole 479 Ipecac 476 Ranitidine 479 Kaolin, pectin 473 Sucralfate 481 Lactulose 475 Sulfasalazine 480 Lansoprazole 479 Tegaserod 472 470 40 Drugs Used in Gastrointestinal Disorders 471 INTRODUCTION TO NORMAL fat receptors in the small bowel inhibits gastric peri- PHYSIOLOGY staltic contractions and retards gastric emptying. The small intestinal motility in the fed state consists The gastrointestinal (GI) tract consists of the esopha- of random slow-wave contractions that result in slow gus, stomach, small intestine, and colon. It processes transit and long contact of food with enzymes and ab- ingested boluses of food and drink and expels waste sorptive surfaces. Intervention by disease or pharmacological wave, termed the interdigestive migrating motor com- therapy may alter function of the GI tract. During discusses drugs employed in the treatment of several GI the migrating motor complex, a peristaltic contraction disorders, emphasizing disease pathophysiology and ring travels from the stomach to the cecum at 6 to 8 cm drug mechanisms of action. In the stomach the contractions sweep From the mid esophagus to the anus, smooth muscle against a widely patent pylorus, permitting the passage surrounds the alimentary canal and is responsible for of undigestible solids. In the small intestine this is to active movement and segmentation of intestinal con- clear the intestine of undigested material: it functions tents. The migrating motor propria, consists of a circular and a longitudinal layer of complex appears to correlate with motilin hormonal muscle. Motilin is From the gastric body to the colon, repetitive spon- a 22–amino acid polypeptide released from the duode- taneous depolarizations originate in the interstitial cells nal mucosa as a regulator of normal GI motor activity. These contractions are primarily minute in the stomach, 12 per minute in the proximal in- retrograde in the proximal colon, allowing segmenta- testine, and 8 per minute in the distal intestine. In the distal colon a creased frequency of contraction in the proximal intes- propulsive mass movement occurs intermittently. This tine forms a gradient of contraction, and intestinal may be stimulated by food ingestion and is termed the contents are therefore propelled distally. Reabsorption of 6 to The underlying intrinsic smooth muscle motility is 7 L occurs within the small bowel, leaving a residual of modulated by neurohormonal influences.

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Simultaneous recordings were made of the mem- brane potential of a PT cell proven lopid 300 mg, and of the LFP in overlying cortical layer 1 trusted 300 mg lopid. Note that the PT cell is regularly depolarized in synchrony with the negative peak of each LFP cycle discount lopid 300mg amex, and occasionally discharges discount 300 mg lopid mastercard. A critical mass of synchronous discharge is recruited via gap junctions linking large numbers of inhibitory interneurons (not shown) generic 300mg lopid visa. Simultaneous LFP in deep layers of area 4, intracellular potential of an unidentified cortical neuron, and histogram of extracellular spikes from a thalamic reticular neuron. Since the earliest effect following the stimulus was a suppression of firing, inhibitory feedback was a key mechanism, as always. The same stimulus also reset ongoing beta rhythm (20 Hz), suggesting a close relationship in the circuitry underlying both oscillatory frequencies. These effects were expressed only during a static motor episode, namely a maintained precision grip. Intrinsic membrane properties of both thalamic and neocortical neurons allow them to oscillate within different frequency spectra, usually in the range of 1–20 Hz. The reticular thalamic neurons oscillate even more readily than thalamic neurons them- selves. Both the thalamic neurons give collaterals to the reticular thalamic nucleus on their way to the cortex, and the cortical pyramidal cells also give collaterals as they return to the thalamus. So the entire circuit includes recurrent inhibitory loops within both the thalamus and cortex, reinforcing intrinsi- cally oscillatory membrane potentials, plus coupling of the thalamus and cortex such that they synchronize in the same rhythm. Modeling reveals that thalamic rhythmicity depends on cortical excitatory input being stronger to reticular thalamic neurons (which are themselves inhibitory) than to thalamocortical projection cells. The thalamocortical circuit initially entrains a small cortical focus, and corticocortical connections dis- tribute the synchronization up to 4 mm in different directions. It had alternating sharp positive peaks and rounded negative waves, as shown in Figure 7. From the start, Gastaut recognized that the mu rhythm was closely allied with beta rhythm; he considered mu an amplified form of beta at half the frequency. The arched shape with the 20-Hz ripple is clearly retained in MEG records (Figure 7. Moreover, higher mu frequencies were not exact harmonics of lower ones; spindles could appear at different moments of time at the 10- and 21-Hz component frequencies. Therefore, the characteristic comb shape of the mu rhythm might be composed of two superposed rhythms with different generators. It is notable that mu and beta rhythms do not engage exactly the same cortical territories. Recording subdural ECoG in humans, Ohara and coworkers observed corticomuscular coherence during isometric contraction of wrist extensor muscles. Copyright © 2005 CRC Press LLC A 40 :µV EEG 0. Some large layer 5 projection pyramidal cells are rhythmically bursting at burst frequencies of 5–15 Hz depending on the level of depolarization. Nevertheless, spontaneous PT cell discharge is only modulated and synchronized by oscillatory potentials; there is much activity that occurs independently of the 10-Hz rhythm. They also noted a secondary tremor frequency of about 25 Hz, which they suggested might be related to beta rhythm. However, they were quick to emphasize an important caveat; the relationship between cortical oscillations and tremor move- ments was sporadic. For example, it was lost when subjects were nervous and apprehensive: the tremor persisted but the mu rhythm virtually disappeared. They concluded that the tremor was driven by “continuous rhythmic subcortical dis- charges” which could momentarily entrain the activity of cortical cells “if the cortex Copyright © 2005 CRC Press LLC was not sufficiently activated. Mechanical properties are recognized as the major determinant of physiological tremor; nevertheless there is a central neurogenic component in about one third of the normal population, observed as synchronized EMG bursts mainly in the 7–13 Hz band. The mechanical component is primarily influenced by inertia and stiffness; it changes according to the body part and loading conditions.

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It is important to note that respiration is further assisted by considerable reduction of the dead-space air discount 300 mg lopid with mastercard. Avertical incision is made downwards from the cricoid cartilage discount lopid 300mg otc, passing between the anterior jugular veins discount lopid 300mg without prescription. Alternatively generic 300 mg lopid free shipping, a more cosmetic transverse skin crease incision cheap lopid 300mg visa, placed halfway between the cricoid and suprasternal notch, is employed. Ahook is thrust under the lower border of the cricoid to steady the trachea and pull it forward. The pretracheal fascia is split longitudinally, the isthmus of the thyroid either pushed upwards or divided between clamps and the cartilage of the trachea clearly exposed. The lower respiratory tract 23 In children the neck is relatively short and the left brachiocephalic vein may come up above the suprasternal notch so that dissection is rather more difficult and dangerous. In contrast, the trachea may be ossified in the elderly and small bone shears required to open into it. If this is not done, major vessels are in jeopardy and it is possible, although the student may not credit it, to miss the trachea entirely. Before joining the lung it gives off its upper lobe branch, and then passes below the pulmonary artery to enter the hilum of the lung. It has two important relations: the azygos vein, which arches over it from behind to reach the superior vena cava, and the pulmonary artery which lies first below and then anterior to it. The left main bronchus is nearly 2 in (5cm) long and passes downwards and outwards below the arch of the aorta, in front of the oesophagus and descending aorta. Unlike the right, it gives off no branches until it enters the hilum of the lung, which it reaches opposite T6. The pulmonary artery spirals over the bronchus, lying first anteriorly and then above it. Clinical features 1The greater width and more vertical course of the right bronchus accounts for the greater tendency for foreign bodies and aspirated material to pass into the right bronchus (and thence especially into the middle and lower lobes of the right lung) rather than into the left. The lungs (Figs 18, 19) Each lung is conical in shape, having a blunt apex which reaches above the sternal end of the 1st rib, a concave base overlying the diaphragm, an extensive costovertebral surface moulded to the form of the chest 24 The Thorax Fig. The right lung is slightly larger than the left and is divided into three lobes—upper, middle and lower, by the oblique and horizontal fissures. The lower respiratory tract 25 Blood supply Mixed venous blood is returned to the lungs by the pulmonary arteries; the air passages are themselves supplied by the bronchial arteries, which are small branches of the descending aorta. They maintain the blood supply to the lung parenchyma after pulmonary embolism, so that, if the patient recovers, lung function returns to normal. The superior and inferior pulmonary veins return oxygenated blood to the left atrium, while the bronchial veins drain into the azygos system. Lymphatic drainage The lymphatics of the lung drain centripetally from the pleura towards the hilum. From the bronchopulmonary lymph nodes in the hilum, efferent lymph channels pass to the tracheobronchial nodes at the bifurcation of the trachea, thence to the paratracheal nodes and the mediastinal lymph trunks to drain usually directly into the brachiocephalic veins or, rarely, indirectly via the thoracic or right lymphatic duct. Nerve supply The pulmonary plexuses derive fibres from both the vagi and the sympa- thetic trunk. They supply efferents to the bronchial musculature (sympa- thetic bronchodilator fibres) and receive afferents from the mucous membrane of the bronchioles and from the alveoli. The bronchopulmonary segments of the lungs (Figs 20, 21) A knowledge of the finer arrangement of the bronchial tree is an essential Table 1The named divisions of the main bronchi. Apical Upper lobe bronchus Posterior { Anterior Lateral Right main bronchus Middle lobe bronchus { Medial { Medial (cardiac) Apical Anterior Lower lobe bronchus { Basal { Lateral Posterior Apicoposterior Upper lobe bronchus { Anterior ↓ Superior Lingular bronchus { Left main bronchus Inferior { Anterior Apical Lower lobe bronchus { Lateral Basal Apicoposterior bronchus 2Posterior bronchus 2 3Anterior bronchus 3Anterior bronchus Middle lobe Lingula 4Lateral bronchus 4Superior bronchus 5Medial bronchus 5Inferior bronchus Lower lobe Lower lobe 6Apical bronchus 6Apical bronchus 7Medial basal (cardiac) bronchus 8Anterior basal 8Anterior basal bronchus bronchus 9Lateral basal 9Lateral basal bronchus bronchus Fig. Each lobe of the lung is subdivided into a number of bronchopulmonary segments, each of which is supplied by a segmental bronchus, artery and vein. These segments are wedge-shaped with their apices at the hilum and bases at the lung surface; if excised accurately along their boundaries (which are marked by intersegmental veins), there is little bleeding or alveolar air leakage from the raw lung surface. The names and arrangements of the bronchi are given in Table 1; each bronchopulmonary segment takes its title from that of its supplying seg- mental bronchus (listed in the right-hand column of the table). The left upper lobe has a lingular segment, supplied by the lingular bronchus from the main upper lobe bronchus.

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