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By K. Sanford. Central State University. 2018.

She is sweating The more difficult question is whether oxime treat- profusely order accutane 30mg on-line acne jeans, vomiting generic accutane 40 mg otc acne 7 year old, and having difficulty breathing. Insecticides can include re- She cannot walk without assistance, and she has a versible carbamate AChE inhibitors or irreversible pulse of 30. Certainly a that the woman had threatened suicide 2 hours ear- quick inquiry to see if the product can be identified lier. Oximes are effective in reactivating AChE inhibited by carbamates as well ANSWER: It is very likely that Pam has ingested an as phosphorylating inhibitors. An addi- treatment does present some risk of its own, and it tional diagnostic test would be to examine the size is not typically used for carbamate poisoning, since of the pupils and test for pupillary reflexes. If it is an the life-threatening stage should pass within a few anti-AChE overdose, the pupils will be constricted, hours. You should immediately prepare for ventila- and they will open only slightly (if at all) when the tory support, as paralysis of the muscles of respira- eye is darkened. So there is no de- atropine, a treatment that typically presents rela- finitive answer to whether to administer an oxime. This will reduce or eliminate many If there is reason to suspect a phosphorylating in- symptoms, including the bradycardia, nausea, hy- hibitor was ingested or the patient is descending potension, sweating, and the component of the res- further into severe respiratory distress, treatment piratory difficulty resulting from bronchoconstric- with an oxime might be warranted. It quate ventilatory support is available, it might be appears that the ingestion occurred in the past 2 better to treat the patient symptomatically. Wonderlin DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Atropine 136 Oxybutynin 137 Cyclopentolate 137 Propantheline 137 Dicyclomine 137 Scopolamine 136 Glycopyrrolate 137 Tolterodine 137 Ipratropium 138 Tropicamide 137 Muscarinic blocking drugs are compounds that se- The control of access to muscarinic receptors in the cen- lectively antagonize the responses to acetylcholine tral nervous system (CNS) by a tertiary amine versus (ACh) and other parasympathomimetics that are medi- quaternary ammonium group is fundamentally impor- ated by activation of muscarinic receptors. The belladonna alka- loids, such as atropine, are the oldest known muscarinic MECHANISM OF ACTION blocking compounds, and their medicinal use preceded Antimuscarinic drugs are competitive antagonists of the the concept of neurochemical transmission. The seven trans- membrane helices of these receptors have a ringlike or- ganization in the cell membrane that forms a narrow CHEMISTRY central cleft where ACh binds. At least seven amino The best known of the muscarinic blocking drugs are the acids from four transmembrane helices have been im- belladonna alkaloids, atropine (Atropine) and scopol- plicated in agonist binding to the muscarinic receptors. They are tertiary amines that con- Some of these residues, particularly a negatively tain an ester linkage. Atropine is a racemic mixture of charged aspartate, interact electrostatically with the DL-hyoscyamine, of which only the levorotatory isomer is positively charged quaternary ammonium moiety of pharmacologically active. Atropine and scopolamine are ACh, whereas other residues are required for binding to parent compounds for several semisynthetic derivatives, the ester moiety. Although the tertiary amine and qua- and some synthetic compounds with little structural sim- ternary ammonium groups of antimuscarinic drugs bind ilarity to the belladonna alkaloids are also in use. All of to the same anionic site on the receptor that agonists the antimuscarinic compounds are amino alcohol esters occupy, these drugs do not fit into the narrow cleft and with a tertiary amine or quaternary ammonium group. Finally, some Tissue or other classes of drugs can act in part as muscarinic an- system Effects tagonists. For example, the antipsychotics and antide- Skin Inhibition of sweating (hyperpyrexia may pressants produce antimuscarinic side effects (e. Visual Cycloplegia (relaxation of ciliary mus- cle); mydriasis (relaxation of sphincter pupillae muscle); increase in aqueous outflow resistance (increases intraocu- PHARMACOLOGICAL ACTIONS lar pressure in many cases of glau- coma) Muscarinic antagonists have no intrinsic activity, and Digestive Decreased salivation; reduced tone and they can produce effects only by blocking the activation motility in the gastrointestinal tract; of muscarinic receptors by muscarinic agonists or by decrease in vagus-stimulated gastric, neuronally released ACh. Therefore, the magnitude of pancreatic, intestinal, and biliary secre- tions the response produced by muscarinic antagonists de- Urinary Urinary retention (relaxation of the de- pends on the existing level of cholinergic activity or on trusor muscle); relaxation of ureter the presence of muscarinic agonists. At these locations, block of the activation of mus- Central nervous Decreased concentration and memory; carinic receptors can increase the tone provided by the system drowsiness; sedation; excitation; ataxia; adrenergic input. Atropine can also facilitate atrioventricular Although muscarinic agonists typically do not exhibit (A-V) conduction and block parasympathetic effects on selectivity among muscarinic receptors (see Chapter the cardiac conduction system and on myocardial con- 12), some muscarinic antagonists are selective in their tractility. Blood Vessels Heart Atropine and other muscarinic antagonists produce Intravenous administration of low doses of atropine or minimal effects on the circulation in the absence of cir- scopolamine often produces slight bradycardia, whereas culating muscarinic agonists. This reflects the relatively higher doses produce tachycardia by directly blocking minor role of cholinergic innervation in determining the parasympathetic input to the sinoatrial node. Atropine can produce Although it has been suggested that the bradycardia re- flushing in the blush area owing to vasodilation. One plau- sible explanation for the paradoxical bradycardia pro- Gastrointestinal Tract duced by low doses of muscarinic blockers is that they block presynaptic muscarinic receptors that normally Muscarinic antagonists have numerous effects on the provide feedback inhibition of the release of ACh. The inhibition of Antagonism of these presynaptic muscarinic receptors salivation by low doses of atropine results in a dry prevents feedback inhibition and increases the release mouth and difficulty in swallowing. Antimuscarinic 136 II DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM drugs also inhibit gastric acid secretion and gastroin- By this mechanism they can block reflex laryngospasm testinal motility, because both processes are partly un- during surgery.

Drugs Acting on the Sympathetic Nervous System 89 Inhibitor: Moclobemide MAO-A Selegiline MAO-B Nor- epinephrine Norepinephrine transport system Effector organ A generic 5mg accutane fast delivery acne qui se deplace et candidose. Monoamine oxidase inhibitor Pain stimulus Local anesthetic effect Controlled Substances Act regulates use of Amphetamine cocaine and Cocaine amphetamine "Doping" Runner-up B accutane 10 mg sale acne extraction dermatologist. Indirect sympathomimetics with central stimulant activity and abuse potential Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. With local ceptors are stimulated, further release use, underperfusion of the vasocon- of norepinephrine is inhibited. Con- stricted area results in a lack of oxygen versely, their blockade leads to uncon- (A). In the extreme case, local hypoxia trolled release of norepinephrine with can lead to tissue necrosis. Howev- tance veins during change from the su- er, after vasoconstriction subsides, reac- pine to the erect position (orthostatic tive hyperemia causes renewed exuda- collapse: " venous return, " cardiac out- tion of plasma fluid into the interstitial put, fall in systemic pressure, " blood space, the nose is “stuffy” again, and the supply to CNS, syncope, p. Besides rebound congestion, may serve to lower tonus of smooth persistent use of a decongestant entails musculature in the prostatic region and the risk of atrophic damage caused by thereby facilitate micturition (p. This inhibition can be put to therapeutic use in antihypertensive treatment (vasodilation! Sympathetic these would exacerbate “anxiety” or activation gives rise to an increase in “stage fright”. When sympathetic Stage fright, however, is not a disease drive is eliminated during! As a rule, this basic struc- lytics are completely absorbed from the ture is linked to an aromatic nucleus by intestines and subsequently undergo a methylene and oxygen bridge. The presystemic elimination to a major ex- side chain C-atom bearing the hydroxyl tent (A). Variation of the cleus determines whether the com- molecule will create a new patentable pound possess intrinsic sympathomi- chemical, not necessarily a drug with a metic activity (ISA), that is, acts as a novel action. At the usual therapeutic dosage, the high con- centration required for these effects will not be reached. None of these blockers is sufficiently selective to per- Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Drugs Acting on the Sympathetic Nervous System 95 Isoproterenol Pindolol Propranolol Atenolol! To a lesser degree, release of epineph- Antiadrenergics are drugs capable of rine from the adrenal medulla is also lowering transmitter output from sym- impaired. Their action is hypotensive (indi- (“pharmacological sympathectomy”), cation: hypertension, p. Disorders of extra- permits rapid penetration through the pyramidal motor function with devel- blood-brain barrier. These adverse effects have ting of systemic arterial pressure at a rendered the drug practically obsolete. It is stored instead lease of both norepinephrine (NE) and of NE, but is unable to mimic the func- acetylcholine. Lassitude, dry mouth; es the axonal membrane, thereby im- rebound hypertension after abrupt ces- peding the propagation of impulses into sation of clonidine therapy. Stor- Methyldopa (dopa = dihydroxy- age and release of epinephrine from the phenylalanine), as an amino acid, is adrenal medulla are not affected, owing transported across the blood-brain bar- to the absence of a re-uptake process. Cardiovascular cri- of methyldopa competes for a portion of ses are a possible risk: emotional stress the available enzymatic activity, so that of the patient may cause sympatho- the rate of conversion of L-dopa to NE adrenal activation with epinephrine re- (via dopamine) is decreased. Reserpine, an alkaloid from the Rauwolfia plant, abolishes the vesicular storage of biogenic amines (NE, dopa- mine = DA, serotonin = 5-HT) by inhibit- ing an ATPase required for the vesicular amine pump. The amount of NE re- Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Inhibitors of sympathetic tone Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Parasympathetic outflow is chan- nelled from the brainstem (1) through Responses to activation of the para- the third cranial nerve (oculomotor n. Parasympathetic via the ciliary ganglion to the eye; (2) nerves regulate processes connected through the seventh cranial nerve (fa- with energy assimilation (food intake, cial n. Approximately 75% of all because of enhanced peristaltic activity parasympathetic fibers are contained and lowered tone of sphincteric mus- within the vagus nerve. To empty the urinary bladder (mic- the sacral division innervate the distal turition), wall tension is increased by colon, rectum, bladder, the distal ure- detrusor activation with a concurrent ters, and the external genitalia.

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When the problem or the reality is extremely complex and optimization techniques are not available generic accutane 5mg with amex acne medication oral, a heuristic may be used cheap accutane 5 mg acne treatment during pregnancy. Heuristics do not yield definitive solutions, but assist decision makers in arriving at provisional solutions (Camms & Evans, 1996). For example, the determination of the choice of initial doses of both medication and dialysis treatment for a renal patient relies on population-based pharma- cokinetic and solute kinetic heuristics, respectively. Rule-based decision support systems primarily store knowledge in the form of rules and problem solving procedures. Rules are applied on the data collected using an inference engine, decisions are suggested, and explanations supplied (Turban & Aronson, 2000). For example, DARWIN, a renal decision support system, uses rule-based reasoning to advise dialysis technical staff regarding the response to bacteriologic monitoring of fluids used during hemodialysis. Another example of a rule-based or expert system is the use of clinical protocols to generate suggestions regarding anemia treatment using erythropoietin and iron protocols. On the basis of knowledge of new and historical laboratory results and medications, the expert system can suggest the modification of drug doses or the discontinuation of a medication. The inference engine can also provide an explanation of the basis of the recommendation in the protocol. A decision algorithm is a set of instructions that is repeated to solve a problem. Highly intelligent algorithms include the capability to learn and to perform several iterations of the algorithm or of parts of the algorithm until an optimal solution is reached (Turban & Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. A very simple decision algorithm may alert physicians on receipt of out- of-range laboratory results. In the next sections, we will discuss about the characteristics of a medical decision support systems, generic components, problem areas in which decision support systems are used and knowledge sharing standards. Characteristics of M edical Decision Support Systems To understand the characteristics of a medical decision support system, it is important to analyze the medical decision making process. A clear understanding of the medical decision making process is essential to appreciate the value and the characteristics of a medical decision support system. It is an extremely complex sequence of inter related and differentiated activities that occur over a period of time. The vastness of the knowledge area presents itself infinite paths to reach a decision. Thus, the importance of finding an optimal path is extremely important in the decision making process. Any assistance in this critical step can be of immense value to the medical decision makers. The second is the beliefs and opinions about the objective states, and the processes including input and outcomes states. The third is the values and consequences attached to each outcome of the event-choice-action combination. The decision support literature classifies problems into three major categories: struc- tured, semi-structured, and unstructured (Gorry & Morton, 1971). Structured problems are routine and repetitive: solutions exist, are standard, and pre-defined. Unstructured problems are complex and fuzzy; they lack clear and straight-forward solutions. Semi- structured problems combine the features of the two previous categories; their solution requires human judgment as well as the application of standard procedures (Simon, 1971). Thus the complexity involved in a decision making process can be grouped as a knowledge gathering process, knowledge storage, knowledge retrieval, and information processing. The literature categorizes the decision making process into four distinct phases: intelligence, design, choice, and review (Stohr & Konsynski, 1992). During the intelligence phase of the decision making process, the need for a decision making (or the trigger) event is recognized and the clinical problem or opportunity is properly identified and defined. This is done by eliciting two different types of knowledge domains: public and private. Private knowledge generally is heuristic and experience- based knowledge that usually comes from the clinical practitioners. Public knowledge can be gathered from standards, guidelines, text books and journals.

Rzhetsky order accutane 5mg overnight delivery acne juvenil, Iossifov buy 20mg accutane free shipping acne 2009 dress, Koike, Krauthammer, Kra, Morris, Yu, Duboue, Weng, Wilbur, Hatzivassiloglou, and Friedman (2004) have recently proposed an integrated system which visualizes molecular interaction pathways and therefore has the ability to make published knowledge literally visible. In the following sections we go into more detail and look how computational methods can deal with text. Representing Text The most common way to represent text data in numerical form such that it can be further processed by computational means is the so-called “bag of words” or “vector space” model. To this end a standard practice composed of two complementary steps has emerged (Baeza-Yates & Ribeiro-Neto, 1999): 1. Indexing: Each document is represented by a high-dimensional feature vector in which each component corresponds to a term from a dictionary and holds the occurrence count of that term in the document. The dictionary is compiled from all documents in the database and contains all unique words appearing throughout the collection. In order to reduce the dimensionality of the problem, generally only word stems are considered (i. Additionally, very frequently appearing words (like “the” & “and”) are regarded as stop words and are removed from the dictionary, because they do not contribute to the distinguishability of the documents. Weighting: Similarities between documents an then be measured by the Euclidean distance or the angle between their corresponding feature vectors. However, this ignores the fact that certain words carry more information content than others. The so-calledtf-idfweighting scheme (Salton & Buckley, 1988) has been found a suitable means to deal with this problem: Here theterm frequencies (tf)in the document vector are weighted with the inverse document frequency idfi = log(N/sd ), where N is the i number of documents in the collection, and sd denotes the number of times the word i stem si occurs in document d. Although the “bag of words” model completely discards the order of the words in a document, it performs surprisingly well to capture its content. A major drawback is the very high dimensionality of the feature vectors from which some computational algo- rithms suffer. Additionally, the distance measure typically does not take polysemy (one word has several meanings) and synonymy (several words have the same meaning) into account. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Interactive Information Retrieval Towards Effective Knowledge Management 59 Evaluating Retrieval Performance In order to evaluate an IR system, we need some sort of quality measure for its retrieval performance. Consider the following situation: We have a collection of C documents and a queryQ requesting some information from that set. Let R be the set of relevant documents in the database to that query, and A be the set of documents delivered by the IR system as answers to the given query Q. The precision and recall are then defined by R A R A precision and recall, R R where R∩A is the intersection of the relevant and the answer set, that is, the set of found relevant documents. The ultimate goal is to achieve a precision and recall value of one, that is, to find only the relevant documents, and all of them. A user will generally not inspect the whole answer set A returned by an IR system—who would want to click through all of the thousands of hits typically returned by a web search? Therefore, a much better performance description is given by the so-called precision-recall-curve. Here, the documents in A are sorted according to some ranking criterion and the precision is plotted against the recall values obtained when truncating the sorted answer set after a given rank—which is varied between one and the full size of A. Therefore, the quality of a search engine which generates hit lists is strongly dependent on its ranking algorithm. In essence, each document (or page) is weighted with the number of hyperlinks it receives from other web pages. At the same time the links themselves are weighed by the importance of the linking page (Brin & Page, 1998). The analogue to hyperlinks in the scientific literature are citations, that is, the more often an article is cited, the more important it is (Lawrence, Giles & Bollacker, 1999). The Role of Context So, we can handle unstructured text and measure how good an IR system works, but a critical question was not answered yet: How do we determine, which documents from a large collection are actually relevant to a given query?

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