By N. Thorus. Southwestern College, Kansas.

It is administered by subcutaneous injection platelet count within the first two days of treatment is once a day quality dapoxetine 90 mg erectile dysfunction solutions pump, at a dose that depends on body weight generic dapoxetine 60mg on line drugs used for erectile dysfunction. 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. Epoprostenol relaxes current therapy is discontinued, catastrophic over-anticoagu- pulmonary as well as systemic vasculature, and this underpins lation and haemorrhage may ensue. Rigorous proof of efficacy is diffi- • haemorrhage (including intracranial, especially in patients cult to provide in such settings. Epoprostenol is infused intra- with uncontrolled hypertension); venously (or, in the case of haemodialysis, into the arterial limb • nausea, vomiting, constipation or diarrhoea; supplying the dialyzer). It is administered with frequent moni- • headache; toring of blood pressure and heart rate during the period of • dizziness, vertigo; dose titration.

Research has also suggested that individuals who respond to placebos are introverted buy 90 mg dapoxetine with visa erectile dysfunction drug therapy. However buy 90 mg dapoxetine otc erectile dysfunction statistics age, many of the characteristics described are conflicting and there is little evidence to support consistent traits as predictive of placebo responsiveness. Characteristics of the treatment Other researchers have focused on treatment characteristics and have suggested that the characteristics of the actual process involved in the placebo treatment relates to the effectiveness or degree of the placebo effect. For example, if a treatment is perceived by the individual as being serious, the placebo effect will be greater. Accordingly, surgery, which is likely to be perceived as very serious, has the greatest placebo effect, followed by an injection, followed by having two pills versus one pill. Research has also looked at the size of the pill and suggests that larger pills are more effective than small pills in eliciting a change. Characteristics of the health professional Research has also looked at the characteristics of the health professional suggesting that the kind of professional administering the placebo treatment may determine the degree of the placebo effect. For example, higher professional status and higher concern have been shown to increase the placebo effect. Problems with the non-interactive theories Theories that examine only the patient, only the treatment or only the professional ignore the interaction between patient and health professional that occurs when a placebo effect has taken place. They assume that these factors exist in isolation and can be examined independently of each other. However, if we are to understand placebo effects then perhaps theories of the interaction between health professionals and patients described within the literature (see Chapter 4) can be applied to understanding placebos. Placebo effects should be conceptualized as a multi-dimensional process that depends on an interaction between a multitude of different factors. To understand this multi-dimensional process, research has looked at possible mechanisms of the placebo effect. Experimenter bias Experimenter bias refers to the impact that the experimenter’s expectations can have on the outcome of a study. For example, if an experimenter was carrying out a study to examine the effect of seeing an aggressive film on a child’s aggressive behaviour (a classic social psychology study) the experimenter’s expectations may themselves be responsible for changing the child’s behaviour (by their own interaction with the child), not the film. Subjects were allocated to one of three conditions and were given either an analgesic (a painkiller), a placebo or naloxone (an opiate antagonist, which increases the pain experience). The patients were therefore told that this treatment would either reduce, have no effect or increase their pain. They either believed that the patients would receive one of three of these substances (a chance of receiving a pain killer), or that the patient would receive either a placebo or naloxone (no chance of receiving a pain killer). Therefore, one group of doctors believed that there was a chance that the patient would be given an analgesic and would show pain reduction, and the other half of doctors believed that there was no chance that the patient would receive some form of analgesia. This study, therefore, manipulated both the patients’ beliefs about the kind of treatment they had received and the doctors’ beliefs about the kind of treatment they were administering. The results showed that the subjects who were given the drug treatment by the doctor who believed they had a chance to receive the analgesic, showed a decrease in pain whereas the patients whose doctor believed that they had no chance of receiving the pain killer showed no effect. This suggests that if the doctors believed that the subjects may show pain reduction, this belief was communicated to the subjects who actually reported pain reduction. However, if the doctors believed that the subjects would not show pain reduction, this belief was also communicated to the subjects who accordingly reported no change in their pain experience. This study highlights a role for an interaction between the doctor and the patient and is similar to the effect described as experimenter bias described within social psychology.

The results showed that both distraction and low anxiety reduced the pain experience discount dapoxetine 60mg amex impotence at 19. Fear Many patients with an experience of pain can have extensive fear of increased pain or of the pain reoccurring which can result in them avoiding a whole range of activities that they perceive to be high risk buy cheap dapoxetine 30 mg on line erectile dysfunction by country. For example, patients can avoid moving in particular ways and exerting themselves to any extent. However, these patients often don’t describe their experiences in terms of fear but rather in terms of what they can and cannot do. Therefore, they don’t report being frightened of making the pain worse by lifting a heavy object, but they state that they can no longer lift heavy objects. Fear of pain and fear avoidance beliefs have been shown to be linked with the pain experience in terms triggering pain in the first place. The participants were then followed up after one year and the occurrence of a pain episode and their physical functioning was assessed. The results showed that 19 per cent of the sample reported an episode of back pain at follow-up and that those with higher baseline scores of fear avoidance were twice as likely to report back pain and had a 1. Some research also suggests that fear may also be involved in exacerbating existing pain and turning acute pain into chronic pain. They argued that pain functions by demanding attention which results in a lowered ability to focus on other activities. Their results indicated that pain related fear increased this attentional interference suggesting that fear about pain increased the amount of attention demanded by the pain. They con- cluded that pain related fear can create a hyper-vigilance towards pain which could contribute to the progression from acute to chronic pain. These conclusions were further supported by a comprehensive review of the recent research. This indicates that treat- ment which exposes patients to the very situations that they are afraid of, such as going out and being in crowds, can reduce fear avoidance beliefs and modify their pain experience (Vlaeyen and Linton 2000). The role of cognition Catastrophizing Patients with pain, particularly chronic pain, in line with many other patients often show catastrophizing. Catastrophizing has been linked to both the onset of pain and the development of longer-term pain problems (Sullivan et al. The results showed some small associ- ations between this and the onset of back pain by follow-up. Their new measure consisted of three subscales reflecting the dimensions of catastro- phizing, namely rumination, magnification and helplessness. They then used this meas- ure to explore the relationship between catastrophizing and pain intensity in a clinical sample of 43 boys and girls aged between 8 and 16. The results indicated that catastro- phizing independently predicted both pain intensity and disability regardless of age and gender. The authors argued that catastrophizing functions by facilitating the escape from pain and by communicating distress to others. Meaning Although at first glance any pain would seem to be only negative in its meaning, research indicates that pain can have a range of meanings to different people. For example, the pain experienced during childbirth although painful, has a very clear cause and consequence. If the same kind of pain were to happen outside of childbirth then it would have a totally different meaning and would probably be experienced in a very different way.