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When electrical activity is absent penegra 50 mg with visa mens health france, resting sinoatrial potential is about −90 millivolts (mv) order penegra on line mens health blog. The three main ions involved with action potential are ■ sodium ■ potassium ■ calcium Extracellular concentrations of about 140 mmol/litre of sodium and 4 cheap penegra on line prostate 24 ingredients. Action potential changes along conduction pathways to ‘overpacing’ lower pacemakers cheap levitra plus 400 mg on-line. This lasts only milliseconds before resting charge of −90 mv (repolarisation) is restored order januvia online now. Action potential of pacemaker cells (sinoatrial node generic zoloft 25mg amex, atrioventricular node and conducting fibres) differs from other myocytes, reflecting the automaticity of pacemaker cells. This prevents cardiac muscle responding to further stimulus, thus ensuring coordinated contraction. Plateau time influences contractile strength of muscle fibres (which determines stroke volume). Hypercalcaemia increases contractility; calcium antagonists can reduce excitability. Catecholamines increase depolarisation (increase duration of phase 4) in pacemaker cells, hence causing tachycardia. Vagal stimulation (mediated through acetylcholine) slows depolarisation (decreases slope in phase 4) of pacemaker cells, causing bradycardia. Atrial/junctional dysrhythmias Sinus arrhythmia This occurs when inspiration increases intrathoracic pressure sufficiently to cause parasympathetic (vagal) stimulation, slowing sinoatrial rate; on expiration, the faster rate is restored. It occurs mainly in children and younger people; high ventilator tidal volumes may cause sinus arrhythmia. Bradycardic children should be given oxygen urgently (unless there are other obvious causes for bradycardia). Obvious causes should be removed, so that oxygen should be optimised (on avoiding oxygen toxicity, see Chapter 18). Drugs include ■ anticholinergics (atropine) block parasympathetic stimulation ■ sympathetic stimulants (adrenaline, isoprenaline). Severe refractory sinus bradycardia may necessitate pacing (temporary or permanent). Young children often have intrinsic (normal) rates exceeding 100 contractions/minute. Cardiac output is usually adequate with rates below 180 beats/min (bpm) provided venous return remains adequate, although rates above 140 bpm are usually treated. Tachycardia reduces diastolic time, and so reduces coronary artery filling time and left ventricular muscle oxygen supply, while increasing left ventricular workload and myocardial oxygen demand.

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The plot is divided into four sections corresponding to the positive and negative values of the parameters penegra 50 mg cheap man health personal trainer. They are used order 50mg penegra with visa mens health 2 minute drill, in conjunction with an already established Hansch equation for a series of related aromatic compounds buy 50mg penegra with visa prostate oncology letters, to select the aromatic substituents that are likely to produce highly active 1 fluticasone 100 mcg generic. For example order viagra vigour 800mg free shipping, suppose that a Hansch analysis carried out on a series of aromatic compounds yields the Hansch equation: log 1=C ¼ 2:67p À 2:56s þ 3:92 (4:13) To obtain a high value for the activity (1/C) it is necessary to pick substituents with a positive p value and a negative s value cheap 20mg accutane. In other words, if high activity analogues are required, the substituents should be chosen from the lower right- hand quadrant of the plot. However, it is emphasized that the use of a Craig plot does not guarantee that the resultant analogues will be more active than the lead because the parameters used may not be relevant to the mechanism by which the analogue acts. It is emphasized that only some of the compounds will be more active than the lead compound. The method is most useful when it is not possible to make the large number of compounds necessary to produce an accurate Hansch equation. However, its use is limited because it requires the lead compound to have an unfused aromatic ring system and it only produces analogues that are substituents of that aromatic system. In addition, the Topliss method also depends on the user being able to rapidly measure the biological activity of the lead compound and its analogues. In both cases the investigation starts with the conversion of the lead into the first analogue at the top of the tree, either the 4-chloro analogue (Figure 4. The activity of this analogue is measured and classified as either less (L), approximately the same (E) or significantly greater (M) than that of the original lead. If the activity is greater than that of the lead the next analogue to be prepared is the next one on the M route. Alternatively, if the activity of the analogue is less than that of the original lead the next step is to produce the analogue indicated by the L route on the tree. Utilisation of Operational Schemes for Analog Synthesis in Drug Design by J G Topliss is followed and the appropriate analogue synthesized. This procedure is repeated, the activity of each new analogue being compared with that of its precursor in order to determine which branch of the tree gives the next ana- logue. It should be realized that only some of the compounds synthesized will be more potent than the original lead A S. The first step in the Topliss approach is to synthesize the 4-chloro derivative (B) of A. Suppose the activity of B is greater than that of A, then following the M branch the Topliss tree (Figure 4. In this case, the Topliss tree shows that the next most promising analogue is the 4-trifluromethyl derivative of (D) of A. At this point one would also synthesize and biologically test the 2,4-dichloro (E) and the 4-nitro analogues (F) of A.

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Schachter’s externality theory suggested that buy penegra 100 mg line prostate zones, although all people were responsive to environmental stimuli such as the sight quality penegra 50mg androgen hormone 2 ep2, taste and smell of food discount penegra american express mens health watches, and that such stimuli might cause overeating buy cheap sildalis 120mg online, the obese were highly and sometimes uncontrollably responsive to external cues cheap super cialis 80 mg otc. It was argued that normal weight individuals mainly ate as a response to internal cues (e discount propecia online visa. Within this per- spective, research examined the eating behaviour and eating style of the obese and non- obese in response to external cues such as the time of day, the sight of food, the taste of food and the number and salience of food cues (e. Research exploring the amount eaten by the obese has either focused on the amount consumed per se or on the type of food consumed. Because it was believed that the obese ate for different reasons than the non-obese it was also believed that they ate more. Research therefore explored the food intake of the obese in restaurants and at home, and examined what food they bought. They weighed all members of the families and found no relationship between body size and the mass and type of food they consumed at home. In an attempt to clarify the problem of whether the obese eat more than the non-obese, Spitzer and Rodin (1981) examined the research into eating behaviour and suggested that ‘of twenty nine studies examining the effects of body weight on amount eaten in laboratory studies. Therefore, the answer to the question ‘do the obese eat more/differently to the non- obese? Over recent years, research has focused on the eating behaviour of the obese not in terms of calories consumed, or in terms of amount eaten, but more specifically in terms of the type of food eaten. Population data indicates that calorie consumption has decreased since the 1970s and that this decrease is unrelated to the increase in obesity (see Figures 15. However, this data also shows that the ratio between carbohydrate consumption and fat consumption has changed; whereas we now eat less carbohydrate, we eat proportionally more fat (Prentice and Jebb 1995). One theory that has been developed is that, although the obese may not eat more than the non-obese overall, they may eat proportionally more fat. Further, it has been argued that not all calories are equal (Prentice 1995) and that calories from fat may lead to greater weight gain than calories from carbohydrates. To support this theory, one study of 11,500 people in Scotland showed that men consuming the lowest proportion of carbohydrate in their diets were four times more likely to be obese than those consuming the highest pro- portion of carbohydrate. A similar relationship was also found for women, although the difference was only two- to three-fold. Therefore, it was concluded that relatively lower carbohydrate consumption is related to lower levels of obesity (Bolton-Smith and Woodward 1994). A similar study in Leeds also provided support for the fat proportion theory of obesity (Blundell and Macdiarmid 1997). This study reported that high fat eaters who derived more than 45 per cent of their energy from fat were 19 times more likely to be obese than those who derived less than 35 per cent of their energy from fat. Therefore, these studies suggest that the obese do not eat more overall than the non-obese, nor do they eat more calories, carbohydrate or fat per se than the non- obese. But they do eat more fat compared with the amount of carbohydrate; the proportion of fat in their diet is higher. As a possible explanation of these results, research has examined the role of fat and carbohydrates in appetite regulation.