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Conformity Behavior and Social Context Conformity pressures may be created when a person is confronted with reactions differing from his own purchase feldene 20mg. Individual reactions under private conditions have been compared with reactions to the same problem in a social context buy feldene 20 mg with mastercard. Properties of social contexts singly or in combination have been studied to determine their effects on increases or decreases in susceptibility buy feldene no prescription. Knowledge of group opinion during the third administration of an attitude questionnaire -231- produced frequency of shifting in the direction of agreement with the majority three times greater than that in the control condition purchase cheap feldene line, with disagreement reduced to approximately one-half of chance expectancy. Gorden (52) evaluated shifts in responses from an initial individual administration of a twelve-item scale of attitudes toward Russia to responses given in the presence of other members. Over half of the subjects shifted toward group opinion, and approximately a third shifted away from it, with no change in the total shift score for approximately an eighth. Helson, Blake, Mouton, and Olmstead (63) reported that naive subjects expressed significantly different degrees of agreement or disagreement with statements matched for degree of militarism as a function and in the direction of prearranged responses by other subjects. Duncker (38) reports that children, responding after one, two, or three other subjects expressed their food preferences, had a selection rate of 81 per cent for foods chosen only 26 per cent of the time earlier in private. Grosser, Polansky, and Lippitt (53) found that a significantly larger number of naive child subjects engaged in unauthorized activities under the influence of perceiving violations by a model in the experimental rather than in the control conditions. Freed, Chandler, Mouton, and Blake (45) have reported similar results in a prohibition situation (see foregoing), as have Barch, Trumbo, and Nagle (5) who observed the behavior of motorists in turning lanes to determine conformance with or violation of a state law requiring turn signals. The behavior of a person following a lead car was significantly related to that of the lead car driver. Blake, Mouton, and Hain (19) obtained similar results for endorsement of a petition (see the foregoing). Frequency of acceptance of a request for volunteers as a function of the perception of acceptance by another person has been investigated by Rosenbaum and Blake (113) and by Rosenbaum (112). Schachter and Hall (117) found that group influences produced greater frequency of volunteering when half the class had been preinstructed to volunteer. Confirmation of these results for public versus private conditions has been reported by Blake, Berkowitz, Bellamy, and Mouton (15). Students first were asked individually to identify which of two cards contained the largest number of dots. After a preliminary show of hands, correct judgments on an individual basis increased from 60 to 64 per cent. Significance of the differences obtained was not evaluated, but findings are consistent with those of later investigations. Clark (28) has reported that 20 per cent of students perceived the "odor" of a bottle of odorless water in the presence of other persons, compared with only 11 per cent in private. The convergence under group conditions of initially divergent responses showed the operation of social influence. Matching a standard line with three variable lines was the task employed by Asch (1) to investigate the influence of erroneous reports on naive subjects. Less than 1 per cent of the responses for the same trials in private was incorrect. By prearranging for reports by seven accomplices to be uniformly incorrect on certain trials, Asch was able to show a significant tendency for naive subjects to shift toward the incorrect position taken by others. Blake and Brehm (16) investigated the effect on naive subjects of hearing the recorded responses of five accomplices. Amount of movement reported for the autokinetic task was varied in magnitude, divergence, and convergence. Pressures created under simulated conditions produced conformity effects apparently similar in character to those created under face-to-face conditions. McConnell and Blake (91) have confirmed this finding, as have Olmstead and Blake (107) for both face-to-face and simulated group conditions. There is evidence that the presence of several other persons giving uniform responses may produce increases in conformity behavior beyond those attributable to the effect of a single other person. The general proposition is that conformity pressures increase with number of other persons present as a negatively accelerated function. Asch (1) varied the number of accomplices giving erroneous reports from one, two, three, four, eight, to sixteen. He reported direct but unequal increments in shifting for increases from one to two to three accomplices but no significant increases for a larger number. Helson (60) arranged for one, two, or three other persons to report their judgments prior to the critical subject. The effect was found to be directly proportional to the number of accomplices giving prior reports. Luchins and Luchins (89) report that, of the group judging after three accomplices reported, 80 per cent showed conformity effects, whereas only 10 per cent shifted their responses after one other accomplice reported. They varied the number of naive subjects present relative to one instructed subject. The confederate was more effective in two- and five-person groups than in three- and four-person groups. Hare (55) investigated the influence of group size on the attainment of consensus, and found that participants in groups of five changed their opinions more toward the group consensus after discussion than those in groups of twelve. No accomplices participated; discussion time was constant, -234- thus giving each member less opportunity to exert influence on others in the larger groups. Three investigators reported no differences in shifting as a function of the number of others participating. Sherif (121) reported no significant differences in the degree of convergence for subjects responding to the autokinetic task in the presence of one or of two other members. Degree of unanimity was not prearranged; the study thus is not comparable to those employing controlled responses by others. Goldberg (49) varied the number of subjects working together in judging the intelligence of persons in nine photographs. Judging in the presence of others produced responses differing significantly from those given under private conditions. No differences in shifting were found for subjects who judged initially in the presence of two or of four other persons. Kidd (76) varied group size from one to two to four to six, and supplied fictitious, imputed norms for each group. Asch (1), in one condition, arranged for the instructed "naive" subject to respond correctly and the instructed majority of six other persons to respond incorrectly. When the person who had been giving the correct report began to agree with the incorrect majority, the frequency of shifting was found to be comparable to that under the condition of routine unanimity. Little shifting from correct reports occurred when, of four other persons reporting prior to the critical subject, two gave correct and two incorrect responses. A significant increase in shifting occurred when all four uniformly gave an incorrect answer. He suggests that the differences between his results and those reported by others may be attributable to the distinctive features of the tasks employed. The effect of the perceived discrepancy on shifting a critical subject away from his -235- private position, and the extent to which the subject shifts toward full agreement with reports by others have been evaluated. Jenness (70) used initial individual judgments of the number of beans in a jar to assign students with initially divergent estimates and those with initially similar estimates to groups of three members and four members respectively. After discussion to arrive at a group estimate, the variation among individual judgments was reduced more in the three-member than in the four-member groups. Festinger, Gerard, Hymovitch, Kelley, and Raven (40), using a labor dispute problem, prior to and during interaction measured the opinions of undergraduate students of the same sex in groups varying from six to nine members; the interaction was controlled by fictitious notes distributed after ten minutes of apparent interchange. Those who perceived themselves as initially disagreeing changed more than those who perceived themselves as initially agreeing with others present. Goldberg (49) has reported significant differences in conformity related to degree of discrepancy, but not for ratio of actual conformity to discrepancy (see foregoing). Wiener (132) reports a relationship between amount of discrepancy from norms and susceptibility, whereas Helson, Blake, and Mouton (61) confirm a positive relationship between the magnitude of discrepancy and the amount of susceptibility (see previous discussion). Greater shifts occurred for the two conditions using the smallest discrepancies between responses.

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These factors appear to have a restraining influence on the prisoner and a liberating one on the interrogator purchase feldene online now. As compared with the citizen discount 20 mg feldene visa, the prisoner must show greater restraint and care in adopting malingering as a solution because of his uncertainty of the effect of such a role order genuine feldene line. In civilian life order cheap feldene line, simulation is attempted partly because of the humanitarian values held by the society. The person hopes that he will be labeled mentally ill, and when this happens, he expects that no further demands will be made on him, that he will not be held responsible for his conduct, and that he will be treated with kindness and care. Mental illness may be considered deviationism or negativism, either in the culture in general or in the interrogation situation in particular. Moreover, the prisoner may have become convinced, and perhaps realistically, that his life depends on his worth to the enemy, and that if he cannot give information, he has no worth. This may make the prisoner reluctant to appear incompetent, or at least completely incompetent, and therefore would act to reduce the amount and degree of malingering. Thus, the prisoner is uncertain that simulation would -296- produce the desired effect, and indeed, there is the danger that if his ruse is accepted, the directly opposite effect might result. The prisoner may be restrained from or reluctant to initiate or continue malingering because of the nature of the prisoner-interrogator relatioaship. The relationship offers the potential for rather great intimacy, and therefore for the development of fear and guilt in the prisoner. Fear may not be as great a component in civil life since the malingerer is assured a great deal of protection. Many people are involved in his case, and appeals are always possible to courts, civil rights boards, mental health commissions, etc. The prisoner of war, however, may be placed in the custody of a single interrogator, or he may be made to believe that it is the interrogator alone who makes all the decisions about his well- being, his value to the enemy, and his fate. With one authority figure who has seemingly unlimited power, the game becomes more dangerous, since the sanctions for being caught in a deception may be immediate and great, and there is no recourse or appeal to other power figures. Thus, the fear of being found out should be greater in the interrogation situation; this should serve to reduce the amount of malingering attempted and possibly reduce the adequacy of the simulation that is attempted. Guilt may become involved because of the closeness which sometimes grows up between the interrogator and the prisoner. Although there may be intense hatred for the interrogator, it is not unusual for warm feelings also to develop. Under such circumstances, the person who attempts malingering may begin to feel that he is taking advantage of the interrogator and may feel some guilt for misleading the one person who seems to be interested in him and who is looking after his welfare. Guilt makes compliance more likely, or at least it increases the likelihood that the prisoner may drop his simulated role. For his part, the interrogator has fewer of the restraints and control than a psychiatric interviewer would have in a democratic society dedicated to humanitarian values. He can easily make the prisoner feel that his life is under his control, and that psychosis or the simulation of psychosis would be punished just as severely as any other type of resistance. Although persons charged with major crimes are malingering in increasing numbers to avoid imprisonment, -297- it seems that simulation by persons charged with less serious offenses is on the decline since these people have realized that being committed to a mental hospital for an indeterminate period can drag out longer than a delineated jail term. Also, the physical techniques for treating mental illness can be quite frightening to a patient; thus it is likely that a malingerer will think twice before allowing himself to be subjected to a course of electroshock treatment and be even more reluctant to undergo a lobotomy. The interrogator is especially free to use these devices as threats, whereas the civilian psychiatrist must consider many other factors. The interrogator has another advantage over his clinical counterpart in civilian life when it comes to reducing the amount of malingering in an entire group of men. When persons charged with crimes are placed together on the same ward while undergoing psychiatric observation prior to trial, there is a great deal of coaching and training occurring among them as they teach one another how to "bug out. The interrogator, however, can keep his prime sources separated so that there is no cross-fertilization, and also he can attempt to extinguish malingering in the group by exposing and punishing an unsuccessful malingerer. Thus he can give himself or the unit the reputation for being a shrewd detector of deception and a harsh punisher of such duplicity. Once the prisoner gets the feeling that his pretense is endangered, the interrogator may supply him with many face-saving devices which would allow him to relinquish the symptoms that prevent him from cooperating, but without forcing him to admit his guilt. Already mentioned was the technique of giving the prisoner "treatment" for his illness, one that is guaranteed to bring about a cure. Thus the prisoner may behave as if the pills or the electroshock did produce a cure or that the hypnosis or narcosis did allow him to recover his memory, and there will be no need to admit the malingering or suffer punishment for it. The prisoner may use this way out if he gets the impression that the interrogator is becoming wise or is demanding recovery. Another honorable way out for the prisoner could be to remain "ill" but not to allow the illness to interfere with the communication of relevant information. The interrogator might allow the prisoner to keep his simulated depression, delusions, or posturing and gesturing, but he would insist that these symptoms in no way interfere with his ability to recall and communicate important facts. To augment -298- this approach, the interrogator might "treat" only those symptoms which cause memory or communication difficulty, reassuring the prisoner that the other symptoms will remain for a while and that he will be hospitalized and be given more care and privileges than he might otherwise receive. This approach makes it possible for the prisoner to cooperate without revealing his deception, and it offers a substitute goal for the malingering — that of better treatment and privileges. Direct confrontation could conceivably produce a real psychic disorder, especially in those persons who are borderline psychotics to begin with and whose symptoms are exaggerations of their own latent tendences. As Hurst (44) and Eissler (22) point out, that which was feigned at one time may show up as a real illness at a later time. If forced compliance to the interrogator would produce more anxiety and guilt than would malingering, a serious disorder may be the alternative which the prisoner will take. Conclusions Detection of Malingering Exact procedures for the determination of malingering are not available. Few true psychotics display the exact symptoms of the textbook cases, and this wide range of variability among psychotics requires evaluations of a wide variety of symptom patterns for the detection of malingering. The malingerer may demonstrate a set of symptoms which must be entertained as a possible deviation from the more usual syndromes. It is only through rather skillful and lengthy observations that an examiner may be able to come to the conclusion -299- that the patient is feigning his condition. Hurst (44) feels that malingering can be diagnosed with certainty only when the simulator is caught flagrante delicto or gives an unforced confession. Eissler (22) doubts the validity of confessions, since psychotics or borderline psychotics may feign malingering. The fact that borderline schizophrenics may try to malinger complicates the matter and makes diagnosis more difficult. Another complicating but undetermined factor is the effect the role may have upon the malingerer. Hurst (44) suggests that what was simulated may become a truly hysterical symptom after a time. There are therapeutic techniques which are dedicated to the proposition that a person may unconsciously take over portions of roles which he has consciously enacted (48, 64). Effectiveness of Malingering as Countermanipulation The advantages of malingering to an individual resisting coercive attempts to influence his behavior lie primarily in the cultural definitions of the psychotic as incompetent and not responsible for his acts. The discouragement of malingering involves principally the creation of the impression that psychosis is no excuse or that the person who is detected in malingering will be treated even more harshly than he might otherwise have been. When the value conflict is sufficiently great, however, neither threat nor actual punishment may be capable of forcing the person to abandon malingering as defense. The prudence in the use of threat and punishment forced on a rational interrogator by the possibility of creating a genuine disorder confers an additional advantage on the malingerer. Risks of Malingering In considering recommendations of malingering as a resistance tactic in training military personnel for the event of capture, certain dangers follow from these same three factors: the cultural definitions of the insane person, the rationality of the interrogator, and the possibility of a genuine disorder being created. Captors may not operate with humane cultural definitions toward the psychotic, and -300- they may not be constrained by rationality in their use of threats and punishments. The risk the malingerer takes must be evaluated in terms of the importance of the goal of resistance and the possible effectiveness of alternative modes of resistance and evasion open to him. The risks involve both the damage the captor may inflict upon him and the possibilities of a real and lasting personality disorder resulting from his simulation. To the best of our knowl- Executive Publisher edge, these procedures reflect currently accepted practice. For individual applications, all recommen- Editorial Director dations must be considered in light of the patient’s clinical David Moreau condition and, before administration of new or infrequently Clinical Director used drugs, in light of the latest package-insert information.

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A series of articles reporting results of studies were published in the Lancet in 1950 feldene 20mg with amex. So were reports on other antihypertensive treatments buy discount feldene online, all relatively new order online feldene, such as the Kempner Rice Diet or a variety of surgical procedures purchase 20 mg feldene otc. Some authors characterized the effect of hexamethonium as ‘medical sympathectomy’. Saville reported the results of a study undertaken at St Martin’s Hospital, Bath, in a well-established clinic for hypertension. The customary treatment over years in this clinic had been rest in bed, sedation, and regular venesection, to which ‘many patients failed to respond signifcantly or to maintain initial improvement’. Five cases of malignant hypertension were experimentally treated with pentamethonium, starting in December 1949, initially in the hospital and later also as outpatients. The aim was to lower the blood pressure enough to relieve symptoms without provoking others due to hypotension. While Saville was reluctant to predict the fnal outcome, she observed that ‘none of the fve cases suffciently treated to date has failed to obtain relief from symptoms’. Saville’s conclusion: ‘The results in 5 patients suggest that pentamethonium bromide may be useful in the treatment of at 11 P. Rosenheim, ‘Effect of Pentamethonium Iodide on Normal and Hypertensive Persons’, Lancet, 254 (1949): 321-323. Turner, ‘“Medical Sympathectomy” in Hypertension: a clinical study of methonium compounds’, Lancet, 56 (1950): 5 - 58. Rosenheim, ‘Lability of Blood Pressure’, Lectures on the Scientifc Basis of Medicine, 1951-1952, 1 (1953): 96-115. On the rice diet, see ‘Diet in Hypertension [editorial]’, Lancet, 255 (1950): 549-560; ‘Rice Diet in Hypertension [editorial]’, Lancet, 256 (1950): 529-530. Sharpey-Schaffer, ‘The Rice Diet in the Treatment of Hypertension: A report to the Medical Research Council’, Lancet, 56 (1950): 509-1. Stanbury, ‘Sympathectomy in Hypertension’, Lancet, 255 (1950): 659-659; ‘Sympathectomy in Hypertension [editorial]’, Lancet, 255 (1950): 768-769. Turner in Edinburgh suggested that ‘methonium drugs have as yet no place in the routine management of patients, though they may prove useful in the treatment of resistant symptoms related to hypertension. We need more information about their precise action, and for the present it will be most proftable to study, in detail, patients who might otherwise be treated by sympathectomy. The Council also mediated between the clinical researchers and the British pharmaceutical companies that provided the drugs, which included Wellcome Burroughs, Allen & Hanbury’s, and more often than the others, May & Baker. Drug companies played a remarkably small and subordinate part in the transformation of the ganglion blockers, quite different from the pro-active role in the development of new drugs that forms part of the image of this industry today. The ganglion blockers provide us with an example for a major pharmaceutical innovation that had its origins in the public sector. Austin Doyle in an article published in 1991, projecting current patterns of drug development on the past, assumed that May & Baker approached clinicians with the request to test the methonium compounds in the clinic. A memo by Green in 1950 illustrates the mechanics of this interaction and the central role of the Council: I telephoned to Dr Forgan [of May & Baker] to ask him to send supplies of pentamethonium and hexamethonium for trial by the mouth in cases of hypertension. He asked whether it would be in order for him to invite Rosenheim to express an opinion on the relative effects of these two substances, as May & Baker have the 17 S. Robertson, ‘Treatment of Severe Hypertension with Hexamethonium Bromide’, British Medical Journal, 256 (1950): 804-806. Turner, ‘“Medical Sympathectomy” in Hypertension: a clinical study of methonium compounds’, Lancet, 256 (1950): 353-358. Doyle, ‘Sir Horace Smirk: Pioneer in Drug Treatment of Hypertension’, Hypertension, 17 (1991): 247-250, p. I said that there would be no objection whatever from our point of view to his asking Rosenheim this or any other question which occurred to him. On a different occasion Green wrote to Paton that [W]e should certainly not regard it as improper for the frm of Geigy – or, indeed, any other frm – to approach Kay and Smith directly on a scientifc question such as you mention. Of course, there is no obligation on Kay and Smith to assist Geigy with advice unless they like to do so. In order to understand the transformation of methonium compounds from experimental drugs to routine treatment for malignant hypertension, in this section I will look at the role of clinicians such as Frederick Horace Smirk at the University of Otago Medical School at Dunedin, New Zealand, who we might want to call a ‘therapeutic enthusiast’. Rasmussen, ‘The Drug Industry and Clinical Research in Interwar America: Three Types of Physician Collaborator’, Bulletin of the History of Medicine, 79 (2005), 50-80; idem, ‘The Moral Economy of the Drug Company-Medical Scientist Collaboration in Interwar America’, Social Studies of Science, 34 (2004), 161-185. Smirk, ‘Organisation of a Hypertensive Clinic, More Particularly For Patients On Methonium Treatment’, October 1951, typescript, p. No other British medical school could have provided during the 1930s a more stimulating environment for those “new men” who were intent on fusing the skills of the laboratory and the clinic. He stayed in Cairo for four years, during which he turned to the search for drugs that had an effect on blood pressure, screening nearly 1,500 commercially available chemicals in stray dogs, with little success. In 1940 he was appointed to the frst full-time chair of medicine at Otago, replacing the part-time professors of systematic and clinical medicine who had retired the previous year. The move towards full-time professors who were expected to be research active paralleled contemporary developments in Britain. He was a scientifc entrepreneur who managed to secure funding for his work from a variety of sources, including pharmaceutical companies. This success was undoubtedly due to his great enthusiasm for pharmaceutical solutions and his success in turning the ganglion blockers into routine drugs. He is also associated with breeding a strain of spontaneously hypertensive rats for laboratory experiments. The greatest coup of his career as research administrator was to secure £1 0,000 from the Wellcome Trust for a completely new clinical research institute in Dunedin in 1960, then among the biggest grants the Trust had ever committed. This was undoubtedly helped by the fact that McMichael by then was a Wellcome Trustee and Green the Trust’s medical secretary. Initially, however, the war years did not make it easy to establish a functioning laboratory in Dunedin. There was hardly any equipment and much had to be improvised, supplies were unreliable, and there was not much space for Smirk and his staff. During the war, Smirk turned to typical war-time research, such as the study of nitrogen mustards and the search for a pharmaceutical treatment 27 F. Fastier, ‘Biography: Sir Horace Smirk: Professor Emeritus’, New Zealand Medical Journal, 67 (1968), 258-265, p. Porter (eds), Companion Encyclopedia of the History of Medicine, London & New York: Routledge, 1993, pp. This search received a boost when in 1949 he spent a sabbatical at the Postgraduate Medical School at Hammersmith Hospital in London, where McMichael was director and professor of medicine. The therapeutic enthusiasts argued that such etiological questions did not matter, as long as lowering the blood pressure appeared to be benefcial. Furthermore, Smirk designed a detailed treatment regime, including quick and simple fxes for the most obvious shortcomings and side effects of ganglion blocker therapy, enabling it to become routine. An important problem of the methonium compounds was their low solubility in water and the resulting low (and unreliable) rate with which the drugs were absorbed into the bloodstream when taken by mouth. Smirk overcame this by devising a regime of subcutaneous injection, a management solution very similar to the administration of insulin to diabetics. Patients had to be ‘titrated’, the right dose found for each individual patient, and this dose adjusted as patient bodies got used to the drug. As the Hull physician Edmond Murphy observed (who, incidentally, characerised Smirk’s attitude towards hexamethonium as ‘enthusiastic’), ‘Smirk and Alstad [one of Smirk’s co-workers in Dunedin] claimed that with adequate parenteral doses – each patient being a law unto himself – a lowered tension can be maintained indefnitely’. Austin Doyle, who joined Smirk’s department in 1952, remembers: Having been working in a traditional way in a British hospital, I was amazed at the confdent and routine way that these diffcult drugs were being used. Blood pressures were then recorded in both postures at 30-minute intervals throughout the day. Patients would attend daily until the correct dose had been attained and would then be allowed to leave, having been supplied with tuberculin syringes, needles, and multidose containers of the drug, which they had been trained to use. Murphy, ‘Treatment of Hypertension with Hexamethonium Bromide’, Lancet, 258 (1951), 899- 901. The multidose containers had been prepared at the university’s pharmacology department by dissolving bulk supplies provided by May and Baker. Some years later, such multidose vials were available pre-packed, directly from the drug producers. Drugs and discipline Hexamethonium, it seems, disciplined doctors, patients, carers, and technicians alike. With intelligent girls who are keen to learn we have experienced no diffculty whatsoever in obtaining from them accurate pressure readings and comments on corresponding symptoms, if any. The ‘standing test’ took advantage of one of the most common side effects of hexamethonium, postural hypotension, a sudden lowering of the blood pressure when patients stood up, which led to dizziness.

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Dose Slow intravenous infusion Adult and child- Haemophilia A; according to patent’s needs order 20 mg feldene. Adverse Efects Allergic reactons including chills; fever; hepatts; anaphylaxis; fulminatng hepatts cheap feldene 20mg. Tranexamic Acid Pregnancy Category-C Schedule H Indicatons Preventon of hemorrhage due to dental procedures in hemophilics generic feldene 20 mg overnight delivery, cyclic heavy menstrual bleeding trusted 20mg feldene, hereditary angioedema, cone biopsy, epistaxis, traumatc hyphema. Dose Dental extracton in Hemophilics: Immediately before tooth extracton, 10 mg/ kg intravenously. Following tooth extracton, intravenous therapy, at a dose of 10 mg/kg body weight three to four tmes daily, may be used for 2 to 8 days. Contraindicatons Hypersensitvity, acquired defectve colour vision, subarachnoid hemorrhage, actve intravascular clotng, pregnancy (Appendix 7c), interactons (Appendix 6c). Retnal venous and arterial occlusion has been reported in patents using tranexamic acid. Adverse Efects Nausea, vomitng, diarhoea, disturbances in colour vision (discontnue), thromboembolic events, allergic skin reactons; giddiness and hypotension on rapid intravenous injecton, headache, backache, musculoskeletal pain. Storage Store protected from light and moisture at a temperature not exceeding 30⁰C. They are there- fore used widely in the preventon and treatment of deep- vein thrombosis in the legs, prophylaxis of embolizaton in rheumatc heart disease and atrial fbrillaton and to prevent thrombi forming on prosthetc heart valves. Heparin is a parenteral antcoagulant that initates antco- agulaton rapidly but has a short duraton of acton. For the treatment of deep venous thrombosis and pulmo- nary embolism heparin is given as an intravenous loading dose followed by contnuous intravenous infusion (using an infusion pump) or by intermitent subcutaneous injecton. Heparin is also used in regimens for the manage- ment of myocardial infarcton, the management of unstable angina, acute peripheral arterial occlusion and in dialysis. In patents undergoing general surgery, low-dose heparin by subcutaneous injecton is used to prevent postoperatve deep-vein thrombosis and pulmonary embolism in high risk patents (those with obesity, malignant disease, history of deep-vein thrombosis or pulmonary embolism, patents over 40 years, those with an established thrombophilic disorder or those undergoing major or complicated surgery). It is also of value in high-risk medical patents, for example obesity, heart failure, when confned to bed. If haemorrhage occurs it is usually sufcient to withdraw heparin, but if rapid reversal of the efects of heparin is required, protamine sulphate is a specifc antdote. Oral antcoagulants take at least 48-72 h for the antcoagulant efect to develop fully; if an immediate efect is needed, heparin must be given concomitantly. Warfarin is indicated in deep- vein thrombosis, pulmonary embolism, for patents with atrial fbrillaton who are at risk of embolizaton and for those with mechanical prosthetc heart valves (to prevent emboli devel- oping on the valves); oral antcoagulants should not be used in cerebral thrombosis or peripheral arterial occlusion as frst- line therapy. If severe haemorrhage occurs, stop warfarin and give phytom- enadione (vitamin K) by Slow intravenous injecton Antcoagulants in Pregnancy: Oral antcoagulants are teratogenic and should not be given in the frst trimester of pregnancy. Women at risk of pregnancy should be warned of this danger since stopping warfarin before the sixth week of gestaton may largely avoid the risk of fetal abnormality. Oral antcoagulants cross the placenta with the risk of placental or fetal haemorrhage, especially during the last few weeks of pregnancy and at delivery. Therefore, if at all possible, oral antcoagulants should be avoided in pregnancy, especially in the frst and third trimester. Difcult decisions may have to be made, partcularly in women with prosthetc heart valves or with a history of recurrent venous thrombosis or pulmonary embolism. Haemophilia: Desmopressin by injecton may aid haemostasis and be useful in mild forms of haemophilia. Dose Intravenous injecton Adult-Treatment of deep-vein thrombosis and pulmonary embolism: loading dose of 5000 units (10,000 units in severe pulmonary embolism) followed by contnuous intravenous infusion of 15 to 25 units/kg/h. Subcutaneous injecton 15,000 units every 12 h; laboratory monitoring is essental, preferably on a daily basis and dose adjusted accordingly. Prophylaxis in general surgery: 5,000 units 2 h before surgery, then every 8 to 12 h for 7 days or untl patent is ambulant (monitoring not needed); during pregnancy (with monitoring) 5,000-10,000 units every 12 h. Note: Not intended to cover prosthetc heart valve management in pregnancy, which requires specialist management. Child-By intravenous injecton: lower loading dose, then by contnuous intravenous infusion; 15 to 25 units/kg/h. Precautons Hepatc impairment (Appendix 7a) and renal failure; hypersensitvity to low molecular weight heparins; spinal or epidural anaesthesia-risk of spinal haematoma; diabetes mellitus; acidosis; concomitant potassium-sparing drugs-increased risk of hyperkalaemia; lactaton; paediatrics; elderly; interactons (Appendix 6c); pregnancy (Appendix 7c). Adverse Efects Immune-mediated thrombocytopenia usually developing 6 to 10 days afer commencement of therapy (requires immediate withdrawal of heparin); haemorrhage; skin necrosis; hypersensitvity reactons including urtcaria; angioedema and anaphylaxis; osteoporosis afer prolonged use and rarely, alopecia; bleeding due to overdose. Menadione Sodium Sulphate (Refer Phytomenadione below) Phytomenadione* Pregnancy Category-C Schedule H Indicatons Antagonist to warfarin; prophylaxis against haemorrhagic disease of the newborn; vit K defciency, hematuria, menorrhagia. Dose Slow intravenous injecton Adult- Warfarin-induced hypoprothrom- binaemia, no bleeding or minor bleeding: 500 µg. Intravenous or intramuscular injecton Child- Neonates: Haemorrhagic disease of the newborn (treatment): 1 mg with further doses if necessary at 8 h intervals (prophylaxis). Oral Child- 2 mg followed by a second dose afer 4 to 7 days and for breasted babies a third dose afer 1 month. Adverse Efects Hypersensitvity reactons including fushing; dyspnoea; bronchospasm; dizziness; hypotension and respiratory or circulatory collapse which may be due to polyethoxylated castor oil surfactant in some injecton formulatons rather than due to phytomenadione. Protamine* Pregnancy Category-C Indicatons Antdote to overdosage with heparin; antdote for heparin in controlled bleeding. Precautons If used in excess protamine has an antcoagulant efect; allergic reactons increased in persons at risk including previous treatment with protamine or protamine insulin; fsh allergies; men who are infertle or who have had a vasectomy; pregnancy (Appendix 7c); lactaton; children. Adverse Efects Nausea; vomitng; lassitude; fushing; hypotension; bradycardia; dyspnoea; allergic reactons (including angioedema; anaphylaxis); allergy specially if previous exposure to protamine insulin; fsh allergy; infertle or vasectomised men. Warfarin* Pregnancy Category-X Schedule H Indicatons Prophylaxis of embolisaton in rheumatc heart disease and atrial fbrillaton; prophylaxis afer inserton of prosthetc heart valve; prophylaxis and treatment of venous thrombosis and pulmonary embolism; transient ischaemic atacks; myocardial infarcton; vulvular heart disease. Dose Oral Adult- Prophylaxis and treatment of thromboembolic disorders; usual inducton dose is 10 mg daily for 2 days, according to the individual patent; the subsequent dose depends upon the prothrombin tme; the usual daily maintenance dose is 3 to 9 mg administered at the same tme each day. For rapid antcoagulaton: initally 10 mg daily for 2 days, maintenance dose 2 to 10 mg daily. Note: Wherever possible, the base-line prothrombin tme should be determined before the inital dose is given. Contraindicatons Pregnancy (Appendix 7c); peptc ulcer; severe hypertension; bacterial endocardits; hypersensitvity; blood dyscrasias; recent surgery; psychosis; pericardial efusion; cerebrovascular disorder; alcoholism; senility; aneurysm. Precautons Heparin induced thrombocytopenia; surgery or trauma; Vit C, K; lactaton; alcoholics; purple toes syndrome; discontnue if necrosis develops; elderly; hepatc impairment (Appendix 7a) or renal failure; recent surgery; lactaton (Appendix 7b); interactons (Appendix 6a, 6b, 6c, 6d). Adverse Efects Haemorrhage; hypersensitvity; rash; alopecia; diarrhoea; unexplained drop in haematocrit; ‘purple toes’; skin necrosis; jaundice; hepatc dysfuncton; nausea; vomitng and pancreatts. In additon, measures such as weight reducton, moderate salt restricton and appro- priate exercise should be introduced. A thiazide diuretc such as hydrochlorothiazide is used in the management of mild to moderate heart failure when the patent has mild fuid retenton and severe pulmonary oedema is not present; however thiazides are inefectve if renal functon is poor. In these patents and in more severe fuid retenton, a loop diuretc such as furosemide is required. In severe fuid retenton, intravenous furosemide produces relief from breathlessness and reduces preload sooner than would be expected from the tme of onset of diuresis. Hypoka- laemia may develop, but is less likely with the shorter-actng loop diuretcs than with the thiazides; care is needed to avoid hypotension. A combinaton of a thiazide and a loop diuretc may be required to treat refractory oedema. The combinaton ofen produces a synergistc efect on solute and water excreton, which relieves symptoms in the diuretc-resistant heart failure patent. However, the combinaton may produce excessive intravascular volume depleton and electrolyte disturbances including potentally life-threatening hypokalaemia. Digoxin, a cardiac glycoside, increases the strength of cardiac muscle contractons and increases cardiac output. In mild heart failure, digoxin inhibits the sympathetc nervous system and produces arterial vasodilaton. It produces symptomatc improvement, increases exercise tolerance and reduces hospi- talizaton, but it does not reduce mortality. Isosorbide dinitrate produces mainly venous dilataton, which reduces lef ventricular preload, leading to a reducton in pulmonary congeston and dysp- noea. Hydralazine produces mainly arterial vasodilaton, which reduces lef ventricular aferload and increases stroke volume and cardiac output.

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