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In many centers order slimex 15 mg without a prescription, it is the second-line drug after digoxin for therapy of fe- Electrophysiological Actions tal arrhythmias cheap slimex 10mg with mastercard. Because of the high incidence of proar- Sinoatrial Node rhythmia purchase slimex 15 mg, initiation of therapy or significant increases in Flecainide decreases the sinus cycle length but re- dosing should be performed only on inpatients buy slimex 10 mg online. Adverse Effects Atrium Flecainide decreases the maximal rate of depolar- Most adverse effects occur within a few days of initial ization in atrial tissue and shifts the membrane respon- drug administration cheap slimex 10 mg with amex. The atrioventricular conduction time, measured as Worsening of heart failure and prolongation of the PR the A–H interval, is prolonged by flecainide as is the His-Purkinje or H–V interval. His-Purkinje System and Ventricular Muscle Contraindications Flecainide slows conduction in the His-Purkinje system and ventricular muscle to a greater degree than Flecainide is contraindicated in patients with preexist- in the atrium. Flecainide may also cause block in acces- ing second- or third-degree heart block or with bundle sory A-V connections, which is the principal mecha- branch block unless a pacemaker is present to maintain nism for its effectiveness in treating A-V reentrant ventricular rhythm. Electrocardiographic Changes Drug Interactions Flecainide increases the PR, QRS, and to a lesser ex- In patients whose condition has been stabilized by fle- tent, QTc intervals. Hemodynamic Effects Propafenone Flecainide produces modest negative inotropic effects that may become significant in the subset of patients Propafenone (Rythmol) exhibits predominantly class with compromised left ventricular function. Additionally, propafenone is a weak Oral bioavailability Nearly complete -receptor and L-type calcium channel blocker. Onset of action 1 hour Peak response 2–3 hours Electrophysiological Actions Duration of action 8–12 hours Plasma half-life 2–10 hours As with all members of its class, propafenone has its ma- Primary route of metabolism Hepatic jor effect on the fast inward sodium current. Inhibition of the sodium channel throughout the cardiac cycle will result in a de- Approved indications for propafenone include treatment crease in the rate of ectopy and trigger ventricular of supraventricular arrhythmias and life-threatening tachycardia. Propafenone has been shown to increase mor- Sinoatrial Node tality in patients with structural heart disease, and so ex- Propafenone causes sinus node slowing that could treme caution must be used in this subset of patients. It may lengthen the sinus node with flecainide, the patient should be hospitalized for recovery time with minimal effects on sinus cycle length. Atrium Adverse Effects and Drug Interactions The action potential duration and ERP of atrial mus- Concurrent administration of propafenone with cle are both prolonged by propafenone. The electrophys- digoxin, warfarin, propranolol, or metoprolol increases iological effects persist beyond removal of the drug from the serum concentrations of the latter four drugs. In patients with atrial flutter, fibrillation, or Cimetidine slightly increases the propafenone serum tachycardia, propafenone can slow the atrial rate, result- concentrations. Additive pharmacological effects can ing in a change from 2:1 or 4:1 A-V block to 1:1 A-V con- occur when lidocaine, procainamide, and quinidine are duction with a subsequent increase in the ventricular rate. As with other members of class IC, propafenone A-V Node may interact in an unfavorable way with other agents The IV administration of propafenone slows con- that depress A-V nodal function, intraventricular con- duction through the A-V node. His-Purkinje System and Ventricular Muscle The most common are dizziness or light-headedness, Propafenone slows conduction and inhibits auto- metallic taste, nausea, and vomiting; the most serious matic foci. Electrocardiographic Changes Contraindications Propafenone causes dose-dependent increases in the Propafenone is contraindicated in the presence of se- PR and QRS intervals. Other contraindications include by an increase in right atrial, pulmonary arterial, and severe bradycardia, hypotension, obstructive pulmo- pulmonary artery wedge pressures in addition to an in- nary disease, and hepatic and renal failure. Because of crease in vascular resistance and a decrease in the car- its weak -blocking action, propafenone may cause pos- diac index. This problem is great- may be observed in patients with preexisting left ven- est in patients who are slow metabolizers. In the absence of cardiac abnor- malities, propafenone has no significant effects on car- diac function. SA, sinoatrial; D, decrease in conduction velocity; I, increase in conduction velocity; –, no significant effect with clinically relevant doses;,mini- mal effect. Bear in mind the com- Atrium plete spectrum of cardiovascular effects of these agents Propranolol has local anesthetic properties and ex- when prescribing their use. For example, while patients erts actions similar to those of quinidine on the atrial with a normally functioning cardiovascular system may membrane action potential. Membrane responsiveness tolerate adrenergic blockade of the heart, patients with and action potential amplitude are reduced, and ex- compensated heart failure, who depend on adrenergic citability is decreased; conduction velocity is reduced. A-V Node Propranolol The depressant effects of propranolol on the A-V node are more pronounced than are the direct depres- Propranolol (Inderal) is the prototype -blocker (see sant effects of quinidine. It decreases the effects of sympathetic dual actions of -blockade and direct myocardial de- stimulation by competitive binding to -adrenoceptors.

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The thrombin liberated in thromboplastin inhibitor buy generic slimex 15mg, a substance that inhibits the process now activates (a) fibrinogen (I) to exogenous activation of coagulation buy slimex 15 mg, and prostacy- fibrin (Ia) buy discount slimex 15 mg, (b) fibrin-stabilizing factor (XIII) 10mg slimex overnight delivery, clin(=prostaglandinI ) 15 mg slimex amex,whichinhibitsplateletadhe-2 and (c) V, VIII and XI (positive feedback). In- which XIIIa ultimately stabilizes to insoluble fi- jectedheparinhasimmediateaction. XIIIa is a transamidase that links marol) are vitamin K antagonists that work by in- the side chains of the fibrin threads via hibiting liver epoxide reductase, which is necessary covalent bonds. Therefore, these drugs do not take effect until the serum concentration of Fibrinolysis and Thromboprotection vitamin K-dependent coagulation factors has decreased. Cyclooxygenase inhibitors, such as To prevent excessive clotting and occlusion of aspirin (acetylsalicylic acid), inhibit platelet aggrega- major blood vessels (thrombosis) and em- tion by blocking thromboxane A2 (TXA2) synthesis bolisms due to clot migration, fibrinS is re-dis- (! Hemorrhagic diatheses can have the following solved (fibrinolysis) and inhibitory factors are causes: a) Congenital deficiency of certain coagula- activated as soon as vessel repair is initiated. The main causes are factor XIIa), tissues (tissue plasminogen acti- liver damage as well as vitamin K deficiency due to vator, tPA, endothelial etc. This bocytopenia) or platelet defect (thrombocy- is useful for dissolving a fresh thrombus lo- topathy). Fibrinolysis Plasminogen Fibrin mesh-work Streptokinase Plasma Staphylokinase kallikrein (PKK) Plasmin XIIa tPa Aprotinin, etc. Kallikrein Tranexamic acid Urokinase α2-Antiplasmin Activates Converts to Inhibits Medication Soluble fibrinopeptides D. Suppression of coagulation Heparin Exogenous Endogenous activation activation PL–Ca2+–VIIa XI XIIa IX XIa X PL–Ca2+–IXa–VIIIa V PL–Ca2+–Xa–Va Negative feedback Prothrombin Thrombin Binding to endothelial thrombomodulin Activates α2-Macroglobulin α -Antitrypsin Fibrin Converts to 1 Inhibits Fibrinopeptides 105 Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. They are surrounded by a version of angiotensin I to angiotensin II dense network of pulmonary capillaries and (! The oxy- (Internal or tissue respiration involves nutrient gen-deficient“venous”bloodofthepulmonary oxidation,! Convection (bulk flow) is artery is thus oxygenated (“arterialized”) and the means by which the body transports gases pumpedbackbythelefthearttotheperiphery. Bothflowsaredrivenbya pumped through the pulmonary and systemic circu- pressure difference. CO times the port gases over short distances of a few µm— arterial–venous O2 difference (avDO )2 —i. As the expiratory individual gas relative to the total volume volume is usually measured, it is also abbre-. The rest, the body maintains a VE of about 8L/min, atmospheric partial pressures in dry ambient with. Gas transport Partial pressures Partial pressures kPa (mmHg) Fraction (L/L) kPa (mmHg) FO2 ≈ 0. To exploit the motion of the diaphragm and Mechanics of Breathing chest for ventilation, the lungs must be able to Pressure differences between the alveoli and follow this motion without being completely theenvironmentarethedriving“forces”forthe attached to the diaphragm and chest. This is exchange of gases that occurs during ventila- achieved with the aid of the pleura, a thin tion. Alveolar pressure (PA = intrapulmonary fluid-covered sheet of cells that invests each pressure;! B) must be lower than the lung (visceral pleura), thereby separating it barometric pressure (PB) during inspiration from the adjacent organs, which are covered (breathing in), and higher during expiration by the pleura as well (parietal pleura). If PB is defined as zero, the al- In its natural state, the lung tends to shrink veolar pressure is negative during inspiration due to its intrinsic elasticity and alveolar sur- and positive during expiration (! Since the fluid in the pressure differences are created through pleural space cannot expand, the lung sticks to coordinated movement of the diaphragm and the inner surface of the chest, resulting in suc- chest (thorax), resulting in an increase in lung tion (which still allows tangential movement volume (Vpulm) during inspiration and a of the two pleural sheets). Ppl, also called intra- phragm, scalene muscles, and external inter- pleural (Pip) or intrathoracic pressure, can be costal muscles. Their contraction lowers (flat- measured during breathing (dynamically) tens) the diaphragm and raises and expands using an esophageal probe (! Theexternalintercostal when the chest expands during inspiration, muscles and accessory respiratory muscles are and decreases during expiration (! During expira- ally does not become positive unless there is tion, the diaphragm and other inspiratory very forceful expiration requiring the use of muscles relax, thereby raising the diaphragm expiratory muscles. The difference between and lowering and reducing the volume of the the alveolar and the pleural pressure (PA -Ppl) chest and lungs. In terms hyperpnea and hypopnea are used to de- deeper breathing, active mechanisms can also scribe abnormal increases or decreases in the play a role in expiration: the internal inter- depth and rate of respiratory movements.

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Data processing is also constrained by criteria of what constitutes a processing need effective 10 mg slimex. Information also exists phenomenally discount slimex 10 mg fast delivery, through the very microstructural variety differentiation that exists in a structured situation trusted 10 mg slimex. The model given in Figure 3 leads to questions about our under- standing of knowledge creation generic slimex 15 mg overnight delivery, and has consequences for the way in which we see knowledge development in organizations discount 10mg slimex with mastercard. For instance, how and through what means are the patterns of meaning formed that enable data to be processed, and information to be coalesced. Further exploration of knowledge processes within organizations can be developed within the context of knowledge management. There is a perhaps a better way than that of Figure 3 to describe the relationship between data, information and knowledge, that comes from an ontological model of viable systems that originates from Schwarz (1997). While data is not information, data classifications or classes can be described as entities that, when woven into a relational pattern can become information when conditioned by knowledge within an action setting. This occurs when information is analyzed, interconnected to other information within a thematic context, and compared to what is already known. A relationship between data, information, and knowledge cannot be considered indepen- dently of an agent that is involved in creating that relationship. Our interest lies in the generic relationship, rather than local detailed relationships between commodity ele- ments that will be different for each agent. It presupposes that the agent has a purpose for inquiry and is involved in the process of either quantitative or qualitative measurement. Qualitative measurement involves conceptual assessment brought together with some form of mapping agent that is capable of generating a possibly complex scale of values that can be assessed as though they are quantitative measurements. Relationship between data, information and knowledge Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. The ontological relationship between data, information, and knowledge Autopoiesis and Autogenesis and contextual manifestation of thematic principles from constrained inquiring knowledge behaviour Existential domain Virtual domain Phenomenal domain Patterns of Relational information Data from structure and knowledge defining decision measuration defining context processes Autogenesis and Autopoiesis and regeneration of evaluative regeneration of network perceived experience of decision processes through data processing Knowledge M anagement The management of knowledge is becoming an important area of interest. However, the question of what constitutes knowledge management may be posed in different ways (Allee, 1997). A traditional meaning approach discusses questions of ownership, control, and value, with an emphasis on planning. Another view is that knowledge is organic, and has a flow, a self-organizing process, and patterns. Knowledge is increasingly recognized as an important organizational asset (Iles, 1999). Its creation, dissemination and application are often now seen as a critical source of competitive advantage (Allee, 1997; Lester, 1996). Cognitive elements operate through mental models that are working worldviews that develop through the creation and manipulation of mental analogies. Mental models like schemata, paradigms, perspectives, beliefs and viewpoints, according to Nonaka and Takeuchi, help individuals perceive and define their world. The technical element of tacit knowledge includes concrete know-how, crafts, and skills. However, explicit knowledge is about past events or objects “there and then,” and is seen to be created sequentially by “digital” activity that is theory progressive. It derives from their model of the conversion process between tacit and explicit knowledge, and results in a cycle of knowledge creation. The conversion process involves four processes: socialization, externalization, combination, and internalization, all of which convert between tacit and/or explicit knowledge. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Typology of knowledge Expression of Explicit Knowledge Tacit Knowledge knowledge type Objective Subjective Nonaka and Rationality (mind) Experiential (body) Takeuchi Sequential (there and then) Simultaneous (here and now) Drawn from theory (digital) Practice related (analogue) Codified, formally transmittable in Personal, context specific, hard to formalize and systematic language. Cognitive (mental models), technical (concrete know-how), vision of the future, mobilization process Formal and transferable, deriving in part Informal, determined through contextual experience. It will Alternative from context related information be unique to the viewer having the experience.

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A gents that potentiate the actions of G A BA in the mitters as scientists who concentrate on this area slimex 15 mg line. Interactions between m onoam ines order 10 mg slimex with amex, (D ) Relieve pain glutam ate discount 10 mg slimex mastercard, and G A BA in schizophrenia: new evi- 6 safe slimex 15 mg. The em er- (B) 6 gence of m odern neuroscience: Som e im plications (C) 15 for neurology and psychiatry 10mg slimex otc. International U nion of Pharm acology nervous system but are not nearly as prom inent in Classification of receptors for 5-hydroxytryptam ine the CNS. C a s e S tudy Drugs and the Newborn m other calls to tell you that her week-old baby cillin G norm ally does not penetrate the blood- A is having convulsions. She says the baby exhib- brain barrier to any extent, this is not usually a ited signs of a serious ear infection soon after birth. H owever, the blood-brain barrier is not A physician prescribed penicillin G that apparently fully developed at birth, and substances that nor- was well tolerated. The signs and sym ptom s of the m ally are excluded from entering the CNS m ay en- ear infection appeared to be greatly reduced, but ter the im m ature brain of the newborn. Seizures are the baby began to have convulsions about an hour a m anifestation of several G A BA antagonists, in- after receiving the last injection of penicillin. Many drugs aid anesthesiol- Contemporary anesthetic management requires (1) ogists in the management and comfort of their patients rapid loss of consciousness, which eliminates awareness, during the perioperative period. These compounds vary memory of pain, anxiety, and stress throughout the sur- in their chemical and physical characteristics and in their gical period; (2) a level of analgesia sufficient to abolish usual routes of administration. There are inhalational the reflex reactions to pain, such as muscular movement agents, including volatile liquids and gases, and intra- and cardiovascular stimulation; (3) minimal and re- venously administered drugs. ANESTHETICS While none of the anesthetic drugs discussed in this Intravenous anesthetics are generally employed to in- chapter possesses all of the features required for ideal duce anesthesia, to provide supplemental anesthesia, or anesthetic management (a summary of these features is to permit anesthesia for short operative procedures. Although in- agents, such as neuromuscular blocking drugs, opioids, travenous (IV) agents produce anesthesia rapidly, most and vasoactive substances. Poor-risk patients with significant systemic disease should be monitored for reactions of greater clinical significance. Most of the IV cially well suited to accomplish the first requirement of drugs used to induce anesthesia are slowly metabolized anesthetic management, rapid induction of uncon- and excreted and depend on redistribution to terminate sciousness. The rate of initial redistri- sia within one or two circulation times after their ad- bution following the administration of a single IV bolus ministration because they rapidly achieve initial high of drug is defined by the half-life (t1/2 ), and is generally concentration in the central nervous system (CNS). It can be said, These drugs enter the brain because they are quite lipid therefore, that redistribution of IV anesthetics to skele- soluble and consequently diffuse rapidly through all bi- tal muscle accounts for the return to consciousness after ological membranes, including the blood-brain barrier. Patients generally In addition, since the brain tissue receives a large pro- awaken 15 to 30 minutes after a single IV injection of portion of the cardiac output, a large proportion of an most of the commonly used IV anesthetics. Tissues with lower blood flow per unit tissue, and bone) require hours to come into equilib- mass will receive and therefore remove proportionally rium with plasma drug concentrations (Fig. Since less anesthetic during the initial phase of drug distribu- the accumulation of anesthetic in body fat is relatively tion. All IV anesthetic drugs in use show this early pat- ical practice to calculate drug dosage on the basis of tern of distribution. Thus, the patient to pass rapidly through the initial stages of an obese patient may receive the same dose of IV anes- anesthesia, and sleep is induced quickly. The initial unequal tissue–drug distribution cannot Since the distribution of blood flow is the dominant persist, however, because physicochemical forces tend factor controlling both tissue drug levels and the accu- to require an eventual establishment of concentration mulation of IV anesthetics, changes in cardiac output equilibria with other less well perfused organs. Because blood flow to the the blood by the less richly perfused tissues or elimi- brain is preserved, a greater proportion of the total dose nated by metabolism and excretion or both, plasma lev- of anesthetic will be delivered to the brain during times els will fall, and the concentration of anesthetic in the of diminished cardiac output, such as in congestive brain will decline precipitously. At such times, smaller 100 Plasma Brain, heart, liver, Adipose, bone, and and kidneys Skeletal muscle and skin connective tissue 50 1/8 15–30 120 Time (min) FIGURE 25. The technique called total intravenous anesthe- 2 sia (TIVA) is done with short-acting drugs so that rapid recovery occurs even after long infusions. The loading 1 and maintenance doses of each agent can be pro- 0 grammed by taking their individual pharmacokinetic Time profiles into consideration. Alveolar tension ration of the procedure, to maintain a plasma level that approaches inspired tension. Many practitioners, however, still prefer to titrate the infusion of intravenous drugs to effect without the use doses of anesthetic must be administered to avoid ex- of computer programming.

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