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With such “critical stenosis discount vasodilan 20mg free shipping blood pressure chart emergency,” compensatory coronary vasodilation is no longer sufficient to meet even moderate increases in myocardial demand. You can get an Acute Myocardial Infarct with fixed stenosis, but usually in a restricted subendocardial pattern, when there are other factors that create an imbalance of myocardial oxygen supply and demand. Caused by acute changes in coronary artery atherosclerotic plaques: superficial erosion, ulceration, rupture, or hemorrhage, usually with superimposed thrombosis. Caused by combinations of changed plaque morphology, thrombus, and vasoconstriction leading to severe but transient reductions in blood flow. Usually are conveniently located where interventional cardiologist can reach them by catheter. The preexisting culprit lesion is often not a severely stenotic and hemodynamically significant lesion prior to its acute change (85% had initial stenosis < 70%). Subendocardial zone is defined as the inner half of the ventricular wall; the portion most poorly perfused. In cases of global hypotension, resulting subendocardial infarcts are usually circumferential. The location, severity, and rate of development of coronary atherosclerotic obstructions. Very sensitive but not specific (because it will also be elevated in skeletal muscle damage). TnT may be more sensitive than TnI because there may be a greater percentage of free TnT in cardiac myocytes. Critical abnormalities in cellular biochemistry and function of cardiomyocytes salvaged by reperfusion. Contractile Dysfunction: Common, Early, Proportional to size of infarct; 10% with cardiogenic shock. Many etiologies; Can also be from distortion of supporting structures rather than valve leaflets. They have have less thrombogenicity but have problems of structural valve deterioration D. Surgery is usually repair rather than replacement and often coupled with mitral valve surgery. Dystrophic calcification without significant lipid deposition or cellular proliferation, a process distinct from but with some features of atherosclerosis 3. Calcifications stiffen cusps and fill the sinuses of Valsalva, preventing full opening. Usually cause is unknown, but associated with collagen disorders: Marfan, Ehler-Danlos, and osteogenesis imperfecta. Microscopic: Myxomatous degeneration (weakened collagen with replacement by acid mucopolysaccharide) L. Heart, skin, brain) autoimmune reaction a few weeks after Group A Strep pharyngitis (usually 5-14 yo) 3. Commissures fuse, the chordae tendineae fuse and shorten, the valvular cusps become rigid. Later degenerative changes may be a nonspecific process: Initial deformity -> further chronic injury. Subacute bacterial endocarditis due to less virulent organisms, usually attacking a deformed valve. Cardiac: 1) Previously deformed valves 2) Prosthetic valves 3) Open heart surgery b. Valve vegetations (composed of thrombus, organisms and leukocytes) can be a source for septic emboli to many organs. Non-bacterial thrombotic “marantic” endocarditis: sterile non-destructive thrombi in debilitated patients d. Anorectic drugs, particularly in combination (Fen-Phen) Fenfluramines augment serotonergic activity; phentermine interferes with the pulmonary clearance of serotonin. Valvular sclerosis associated with carcinoid tumors that produce bioactive molecules, such as serotonin and bradykinin. Affects the endocardium downstream from the tumor; then cleared by monoamine oxidase present in microvasculature 3. The kidney may be divided into 2 layers: an outer layer called the cortex and an inner layer called the medulla.

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Figure 9: Alteration in the isometric contraction of isolated cardiac muscle following an increase in contractile state discount vasodilan 20mg on line blood pressure during heart attack. An increase in both force development and maximum rate of force development usually occur when contractile state is changed. By convention, the maximum rate of force development is the preferable index of contractile state. This higher rate of force development goes along with increases in enzyme activity. Those which increase contractility are called positive inotropic interventions, whereas those which decrease contractility are called negative inotropic interventions. In general, most factors which enhance contractile state do so by increasing calcium availability to the myofilaments. Factors which increase contractile state: Factors which decrease contractile state: Incr. Increasing heart rate increases contractility by making more calcium available to the myocardium due to the increased number of depolarizations. The relationship between the rate of contraction and the force developed is termed the force interval relation. In most mammalian species an increase in heart rate will increase cardiac contractility (Figure 10). Figure 10: Isometric twitches of cardiac muscle (B) An increase in stimulation frequency increases contractile state. Many different interventions increase contractility, but there is a limit to which contractility can be increased. Thus, if contractility is increased by one intervention, a second intervention will have a lesser effect as one approaches the ceiling of contractility. Both demonstrate the same principles; Figure 11a is just simpler and in one dimension. Figure 11b shows a schematic diagram of the kind of lever system used to obtain/tonic contractions in isolated heart muscle. The other end of the muscle is attached by a thread to the tip of a lever system which rotates around a fulcrum. When the stop at the upper left is raised out of the way, any load placed on the right-hand side of the lever will stretch the muscle to a length appropriate to its resting length-tension relation. The relative length of the lever arms are used appropriately to calculate the correct preload. With the preload in place and the muscle stretched to an initial length, the stop is then slowly lowered until it just touches the upper left-hand portion of the lever. When any additional load (afterload) is placed on the right- hand side of the lever, the lever can no longer stretch the muscle any further since it is prevented from doing so by the stop. Force rises until the developed force matches the afterload, at which point force remains constant (isotonic) while the muscle shortens. The slope of the shortening trace is the velocity of shortening for that particular load. If one alters the afterload over a wide range, the series of contractions which occur are superimposed in Figure 13 Muscle Mechanics - Robert Turcott, M. The dashed lines between the shortening and tension traces connect the corresponding traces for each contraction. As the afterload is increased, both the distance shortened and the velocity of shortening are reduced. The relation between the load and the distance the muscle shortens is shown in a representative muscle in Figure 14. It is clear from this figure that one way to increase muscle shortening is to reduce the load which the muscle has to lift. Reduction of the afterload increases the cardiac output to the body, and can ameliorate some of the signs and symptoms of heart failure. If one takes the values for velocity of shortening and loading from each of the individual contractions and replots them as a force- velocity relation, the general relationship is a hyperbolic curve (Figure 15).

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Antipsychotic Drugs and Interactions 193 is associated with a baseline of low initiative cheap 20 mg vasodilan amex pulse pressure 18, simple thinking, passivity, emotional withdrawal, anhedonia, lack of spontaneity, poor attention, and/or more impoverished expression, or negative symptoms (41). Perhaps these qualities reflect that dopamine activity in the frontal lobe is diminished to begin with, even before the patient takes medicines (42). For this reason, medication side effects on the frontal lobe, particularly because they are subtle to begin with, commonly go unnoticed. Further complicating the afore- mentioned overlap is the resemblance of these symptoms to depression, and to a lack of stimulation resulting from the abandonment of many with this condition. The standard for care in psychiatry has not achieved the attentiveness to schizo- phrenia that mandates neurocognitive testing of those being medicated with dopamine blockers in order to ensure that cognitive effects independent of the disease process can be accounted for. However, as our sensitivity to the functional rights of our patients improves, this seems to be an appropriate objective—certainly in line with informed consent. Antipsychotics, Cognition, and Implications for Criminal Law Impaired cognition can be especially relevant in the appraisal of a defendant’s abil- ity to render a knowing and intelligent confession. Cognitive impairment may impact a defendant’s competency, or his or her criminal responsibility. The limited cognitive flexibility of those with schizophrenia and the subduing qualities of dopamine blockade do not include a suspension of morality. Antipsycho- tic-induced cognitive changes, pertinent to the aforementioned issues, pale in impor- tance to the cognitive processes of the underlying disease. It is not the dopamine blockade that impacts mental competency for specific tasks within the course of a criminal case, but the underlying condition may be relevant, especially if the legal issues are nuanced and the deficits are pronounced. Cognitive problems associated with some traditional antipsychotics have been attrib- uted to the anticholinergic properties of the given medicines, in addition to effects on dopamine transmission in the cortex (43). Chlorpromazine, thioridazine, and mesoridazine each possess higher anti- cholinergic qualities, and are more sedating as well (45). Higher doses of antipsychotics cause increased sedation, at which point all cognitive domains are affected (45). In the unusual circumstance of anticholinergic toxicity, confusion may be impli- cated in crime, particularly a disorganized event. An acute change in mental status, such as would be seen in a delirium associated with anticholinergic drug toxicity, would give reason to question competency to waive Miranda. The fast reversibility of this drug effect, however, renders this of unlikely consequence in cases of questioned trial or sen- tencing competency. Antipsychotics, Cognition, and Implications for Civil Law Impaired cognition associated with the effects of traditional antipsychotics may be responsible for motor-vehicle or heavy-equipment accidents that kill or injure the patient or someone else. In other instances, work proficiency may be affected, result- ing in the loss of a job. The cognitive effects of the underlying condition are of more likely pertinence to problems people experience in these matters. However, presuming parental, contract, and other incompetence on the basis of even an advanced presentation of schizophrenia—without a specific assessment relating to capacity—is unfair and professionally irresponsible. Atypical antipsychotics may impact cognition as well; these effects are more directly related to the sedating qualities of the medicines, however, than anticholiner- gic properties (46). Clearly, however, there are cognitive advantages to the atypical anti- psychotics, which we will review and explain below. Other Dopamine Blockade Side Effects of Note Dopamine transmission from the hypothalamus to the anterior pituitary is also blocked by traditional antipsychotics (47). Indirectly, therefore, dopamine blockade results, through this mechanism, in unexpected breast secretions, or galactorrhea, menstrual interruption, and amenorrhea (47). Sexual dysfunction occurs in a number of individuals taking dopamine-blocking antipsychotics (48). Whether elevated prolactin levels—or direct effects of dopamine blockade on the sexual-arousal cycle—are responsible, has not yet been determined. Nevertheless, atypical antipsychotics that do not cause a rise in prolactin levels have and have not been shown to be associated with sexuality effects (49). Closer attention to the sexual-arousal cycle is necessary in order to sort out the potential troubles that both traditional and atypical antipsychotics can cause. After dis- cussing neurotransmitters other than dopamine, we will focus on sexuality later in the chapter, as well as the civil forensic implications. Acetylcholine Blockade Through Antimuscarinic Effects In addition to the cognitive side effects noted previously, anticholinergic effects also include dry mouth, blurred vision, constipation, and urinary retention (50).

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