Mark Corson

By Q. Grobock. Ursinus College.

These were the Orgogozo Neurological Index for the stroke patients (Orgogozo et al atorlip-20 20 mg without prescription. Disability and handicap: All patients completed the Sickness Impact Profile (Bergner et al cheap atorlip-20 20mg mastercard. Stroke patients also completed the Barthel index (Mahoney and Barthel 1965) which was complemented with the Observer Assessed disability (Partridge et al purchase atorlip-20 20mg on-line. The psychometric properties of these new scales were then assessed for reliability and validity. Data analysis Data was analysed to assess whether the three concepts could be considered separate and then to examine any causal relationships between them. This analysis showed that impairment did not predict disability and handicap suggesting that there is not a simple causal progression between the different consequences of disease. The authors argue that the transition between impairment, disability and handicap may involve a multitude of other variables not described by the model. In particular, they suggest that the transition from initial impairment through to being limited in social functioning may relate to psychological factors. The authors argue that this is also the case for people with some form of impairment, it is just that their impairment may influence these psychological factors. There is much variability in the ways in which people experience and manage their illness. Psychological factors may be a better explanation of this variation than a simple transition through a series of stages. In addition, stopping smoking can halve the risk of another heart attack in those who have already had one. It has been suggested that the 20 per cent of a population with the highest cholesterol levels are three times more likely to die of heart disease than the 20 per cent with the lowest levels. Cholesterol levels may be determined by the amount of saturated fat consumed (derived mainly from animal fats). Cholesterol reduction can be achieved through a reduction in total fats and saturated fats, an increase in polyunsaturated fats and an increase in dietary fibre. It has been suggested that a 10 mmHg decrease in a population’s average blood pressure could reduce the mortality attri- butable to heart disease by 30 per cent. Blood pressure appears to be related to a multitude of factors such as genetics, obesity, alcohol intake and salt consumption. Other possible behavioural risk factors include exercise, coffee, alcohol and soft water consumption. Type A behaviour and its associated characteristic, hostility is probably the most extensively studied risk factor for coronary heart disease (see Chapter 11 for details). However, interventions have also been developed to reduce stress in non patient samples. For example, Jones and John- ston (2000) developed and evaluated a stress management intervention to reduce distress in 79 student nurses who had previously reported significant distress. The results showed that the intervention produce significant reductions in anxiety, depression and domestic satisfaction. Kaluza (2000) evaluated an intervention designed to change the coping profiles of 82 healthy working men and women. The intervention lasted for 12 weeks and focused on assertiveness, cognitive restructuring, time man- agement, relaxation, physical activities and the scheduling of pleasant activities. The results showed significant improvements in emotion focused coping and problem focused coping which were related to the individual’s original coping profiles. In particular, those who were originally more problem focused became more emotion focused and those who were more avoidant copers became more problem focused. Modifying exercise Most rehabilitation programmes emphasize the restoration of physical functioning through exercise with the assumption that physical recovery will in turn promote psychological and social recovery. Meta-analyses of these exercise-based programmes have suggested that they may have favourable effects on cardiovascular mortality (e. However, such meta-analyses are problematic as there is a trend towards publishing positive results, thereby influencing the overall picture. In addition, whether these exercise-based programmes influence risk factors other than exercise, such as smoking, diet and type A behaviour, is questionable. Modifying type A behaviour The recurrent coronary prevention project was developed by Friedman et al. This programme was based on the following questions: Can type A behaviour be modified? If so, can such modification reduce the chances of a re-occurrence of a heart attack? Subjects had all suffered a heart attack and were allocated to one of three groups: cardiology counselling, type A behaviour modification or no treat- ment. Type A behaviour modification involved discussions of the beliefs and values of type A, discussing methods of reducing work demands, relaxation and education about changing the cognitive framework of the individuals. Modifying general lifestyle factors In addition, rehabilitation programmes have been developed which focus on modifying other risk factors such as smoking and diet. The results showed that after two months, the patients who had received health education and counselling reported a greater increase in physical activity and a greater decrease in unhealthy eating habits. In addition, within those subjects in the experimental condition (receiving health education and counselling), those whose partners had also participated in the programme showed greater improvements in their activity and diet and, in addition, showed a decrease in their smoking behaviour. At 12 months, subjects who had participated in the health education and counselling programme maintained their improvement in their eating behaviour. The authors concluded that, although this study involved only a small number of patients, the results provide some support for including health education and counselling in rehabilitation programmes. More recently, how- ever, van Elderen and Dusseldorp (2001) reported results from a similar study which produced more contradictory results.

Uncontrollable events: If a stressor can be predicted and controlled then it is usually appraised as less stressful than a more random uncontrollable event generic atorlip-20 20mg on-line. For example discount atorlip-20 20mg overnight delivery, experimental studies show that unpredictable loud bursts of noise are more stressful than predictable ones (Glass and Singer 1972) 20mg atorlip-20 overnight delivery. Self-control and stress Recently, theories of stress have emphasized forms of self-control as important in under- standing stress. This is illustrated in theories of self-efficacy, hardiness and feelings of mastery. In 1987, Lazarus and Folkman suggested that self-efficacy was a powerful factor for mediating the stress response. Self-efficacy refers to an individual’s feeling of confidence that they can perform a desired action. Research indicates that self-efficacy may have a role in mediating stress-induced immunosuppression and physiological changes such as blood pressure, heart rate and stress hormones (e. For example, the belief ‘I am confident that I can succeed in this exam’ may result in physiological changes that reduce the stress response. This shift towards emphasizing self-control is also illustrated by Kobasa’s concept of ‘hardiness’ (Kobasa et al. Hardiness was described as reflecting (a) personal feelings of control; (b) a desire to accept challenges; and (c) commitment. It has been argued that the degree of hardiness influences an individual’s appraisal of potential stressors and the resulting stress response. Accordingly, a feeling of being in control may contribute to the process of primary appraisal. Karasek and Theorell (1990) defined the term ‘feelings of mastery’, which reflected an individual’s control over their stress response. In summary, most current stress researchers consider stress the result of a person environment fit and emphasize the role of primary appraisal (‘is the event stressful? This research has highlighted two main groups of physiological changes (see Figure 10. This results in the production of catecholamines (adrenalin and noradrenalin, also known as epinephrine and norepinephrine) which cause changes in factors such as blood pressure, heart rate, sweating and pupil dilation and is experienced as a feeling of arousal. Catecholamines also have an effect on a range of the bodies tissues and can lead to changes in immune function. This results in the production of increased levels of corticosteroids the most important of which is cortisol which results in more diffuse changes such as the management of carbo- hydrate stores and inflammation. These changes constitute the background effect of stress and cannot be detected by the individual. They are similar to the alarm, resistance and exhaustion stages of stress described by Seyle (1956). In addition, raised levels of the brain opiods beta endorphin and enkaphalin have been found following stress which are involved in immune-related problems. The physiological aspects of the stress response are linked to stress reactivity, stress recovery, the allostatic load and stress resistance. Stress reactivity Changes in physiology are known as ‘stress reactivity’ and vary enormously between people. For example, some individuals respond to stressful events with high levels of sweating, raised blood pressure and heart rate whilst others show only a minimal response. This, in part, is due to whether the stressor is appraised as stressful (primary appraisal) and how the individual appraises their own coping resources (secondary appraisal). However, research also shows that some people are simply more reactive to stress than others, regardless of appraisal. Two people may show similar psychological reactions to stress but different physiological reactions. In particular, there is some evidence for gender differences in stress reactivity with men responding more strenu- ously to stressors than women and women showing smaller increases in blood pressure during stressful tasks than men (Stoney et al. Stress reactivity is thought to be dispositional and may either be genetic or a result of prenatal or childhood experiences. However, there is great variability in the rate of recovery both between individuals as some people recover more quickly than others and within the same individual across the lifespan. Allostatic load: Stress recovery is linked with allostatic load which was described by McEwan and Stellar (1993). They argued that the body’s physiological systems constantly fluctuate as the individual responds and recovers from stress, a state of allostasis, and that as time progresses recovery is less and less complete and the body is left increasingly depleted. Stress resistance: To reflect the observation that not all individuals react to stressors in the same way, researchers developed the concept of stress resistance to empha- size how some people remain healthy even when stressors occur (e. Stress resistance includes adaptive coping strategies, certain personality characteristic and social support. Stress reactivity, stress recovery, allostatic load and stress resistance all influence an individual’s reaction to a stressor. Laboratory setting Many stress researchers use the acute stress paradigm to assess stress reactivity and the stress response. This involves taking people into the laboratory and asking them either to complete a stressful task such as an intelligence test, a mathematical task, giving a public talk or watching a horror film or exposing them to an unpleasant event such as a loud noise, white light or a puff of air in the eye. The acute stress paradigm has enabled researchers to study gender differences in stress reactivity, the interrelationship between acute and chronic stress, the role of personality in the stress response and the impact of exercise on mediating stress related changes (e. Naturalistic setting Some researchers study stress in a more naturalistic environment. Naturalistic research also examines the impact of ongoing stressors such as work-related stress, normal ‘daily hassles’, poverty or marriage conflicts.

Their main use is to treat and prevent haemophilia or thrombocytopenic purpura buy atorlip-20 20mg lowest price, or in thrombosis order atorlip-20 20 mg online. Coagulation involves the between platelet activation and the coagulation cascade generic atorlip-20 20 mg overnight delivery, so it is sequential activation of a cascade of clotting factors which not surprising that anticoagulants can also have beneficial effects amplifies a small initial event to produce a macroscopic plug in the prevention of coronary artery disease, or that antiplatelet of fibrin. Each factor is present in blood as an inactive zymo- drugs have some (albeit a minor) effect on venous thrombosis. After activation (indicated by the letter ‘a’ after the Roman numeral that designates the zymogen), several of the Haemostasis is achieved by an exquisitely balanced series factors acquire proteolytic activity. The unfractionated prepara- least as safe and effective as unfractionated products, except tion is extracted from the lung or intestine of ox or pig, in patients with renal impairment. They have largely replaced unfractionated heparin in unfractionated heparin in a meta-analysis of six trials) and pul- therapy. They are at least as effective as unfractionated • to prevent formation of thrombus (e. It is administered • Administration should be stopped and the bleeding site either as an intravenous infusion (to treat established disease) compressed. Intramuscular • Protamine sulphate is given as a slow intravenous injection injection must not be used because it causes haematomas. For prophylaxis, a low dose is injected subcutaneously into the fatty layer of the lower abdomen 8- or Pharmacokinetics 12-hourly. Coagulation times are not routinely monitored when Heparin is not absorbed from the gastro-intestinal tract. Continuous intra- elimination half-life (t1/2) of unfractionated heparin is in the venous infusion is initiated with a bolus followed by a constant range 0. Heparin also binds non-specifically to endothelial cells, range, and thereafter at least daily. The short t1/2 means that a stable plasma concen- Mechanism of action tration is best achieved by a constant infusion rather than by The main action of heparin is on the coagulation cascade. As an antithrombin drug, it Fondaparinux is a synthetic pentasaccharide that selectively inhibits platelet activation by thrombin, but it can also cause binds and inhibits factor Xa. It is more effective than low- platelet activation and paradoxical thrombosis by an immune molecular-weight heparin in preventing venous thrombo- mechanism (see below). It is administered by subcutaneous injection platelet count within the first two days of treatment is once a day, at a dose that depends on body weight. It is a direct • skin necrosis at the site of subcutaneous injection after inhibitor of thrombin and is more specific than heparin. Phenindione is an alternative, but has a number of severe and distinct adverse effects (see Mechanism of action below), so it is seldom used except in rare cases of idiosyn- Oral anticoagulants interfere with hepatic synthesis of the cratic sensitivity to warfarin. Use Preformed factors are present in blood so, unlike heparin, oral anticoagulants are not effective in vitro and are only active The main indications for oral anticoagulation are: when given in vivo. This is formed • atrial fibrillation (see Chapter 32); by carboxylation of a glutamate residue in the peptide chain of • mitral stenosis; the precursor. This cycle is interrupted by warfarin, which is structurally closely Treatment of deep-vein thrombosis and pulmonary embolus related to vitamin K, and inhibits vitamin K epoxide reductase. This is usually continued for up to seven days to allow stabilization Adverse effects of the warfarin dose. Haemorrhage If severe, vitamin K is administered is the prothrombin time corrected for an international stand- intravenously, but its effect is delayed and it renders the ard for thromboplastin reagents. Protein C has a short measured daily, and on the morning of day 3 about 50% of elimination half-life, and when warfarin treatment is patients will be within the therapeutic range and the heparin started, its plasma concentration declines more rapidly can be discontinued. Adverse effects of phenindione: evidence of bleeding, to avoid contact sports or other situ- • interference with iodine uptake by the thyroid; ations that put them at increased risk of trauma, to avoid alco- • renal tubular damage; hol (or at least to restrict intake to a moderate and unvarying • hepatitis; amount), to avoid over-the-counter drugs (other than parac- • agranulocytosis; etamol) and to check that any prescription drug is not • dermatitis; expected to alter their anticoagulant requirement. Appropriate target ranges Pharmacokinetics for different indications reflect the relative risks of thrombo- Following oral administration, absorption is almost complete sis/haemorrhage in various clinical situations. There is Arachidonic acid substantial variation between individuals in warfarin t1/2. The (active) S enantiomer is metabolized to 7-hydroxywarfarin by a Cyclo-oxygenase cytochrome P450-dependent mixed function oxidase, while the less active R enantiomer is metabolized by soluble enzymes to Prostaglandin warfarin alcohols. Hepatic metabolism is followed by conjuga- endoperoxides tion and excretion into the gut in the bile. Since warfarin acts by inhibiting synthesis of active vitamin K-dependent clotting fac- Vasodilatation Vasoconstriction tors, the onset of anticoagulation following dosing depends on the Inhibition of platelet aggregation Platelet aggregation catabolism of preformed factors. These two products of arachidonic acid metabolism exert competing and opposite physiological effects. Drug interactions Potentially important pharmacodynamic interactions with war- in the treatment and prevention of ischaemic heart disease is farin include those with antiplatelet drugs. Numerous clinical trials have demon- influences haemostasis by its effect on platelet function, but also strated its efficacy. Efficacy is not directly related to dose and increases the likelihood of peptic ulceration, displaces warfarin low doses cause less adverse effects. Despite these potential problems, recent clinical exper- further platelet activation) and on vascular smooth muscle ience suggests that with close monitoring the increased risk of (causing vasoconstriction). The most common side effect is suppressing the synthesis of vitamin K1 by gut flora. It acts on specific receptors on the plasma mem- mycin, ciprofloxacin and omeprazole (Chapter 5). These are induce hepatic microsomal enzymes, including rifampicin, coupled by G-proteins to adenylyl cyclase.