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You are divorced and would like to make friend. In a business trip to another city, you meet a very attractive woman who decided to "romance". At a crucial moment does not work. Most likely, you have "tension before going on stage, or fear of failure, or fear of contracting AIDS.

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Whatever the cause, Erectile Dysfunction is often a profound impact on morale. Usually harder to treat psychological reasons than most physical. For example, Erectile Dysfunction caused by medications, easily reversible, and circulatory disorders can sometimes be surgically removed, but when anxiety is associated with the nerves, outlook encouraging. But even if Erectile Dysfunction is really irreversible, for any reason, there is still hope. Currently, there are penile implants of various configurations, they will give "masculine sense" almost anyone.

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Premature ejaculation when orgasm occurs very quickly, is different from Erectile Dysfunction. Men with this problem are capable of erection and the introduction member, and therefore are not considered appropriate vascular, nervous or hormonal causes. In most cases, the causes of premature ejaculation - emotional or mental. Although it is difficult to treat this condition more amenable to psychotherapy than Erectile Dysfunction. Today meditsyne not know any other medicines or illness that is responsible for premature ejaculation.
Female frigidity

Women with a lack of sexual desire and / or reaction to him their partners called frigid, "cold". In many cases, the causes of physical and related to the fact that sexual intercourse causes pain or discomfort. In the article "The painful sexual intercourse" discussed in detail the possible causes and various structural abnormalities of the vagina, as well as the most common types of gynecologic infections and diseases that may affect the sexual pleasure in women. But quite often "female sexual dysfunction has a psychological origin.

Effect of inhibitors of PDE-5 on the cardio-vascular system attracted the attention of researchers from the very beginning of study. Of particular importance of research in this area have given reports on the development of myocardial infarction in men taking sildenafil. Despite the fact that further studies have not confirmed the increased risk of myocardial infarction and sudden cardiac death after administration of inhibitors of PDE-5, the effect on the heart continues to be studied.

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The effect of PDE-5 inhibitors on the myocardium remains controversial. Most studies in this field were performed using the myocardium of animals, with the effect of sildenafil was accompanied by arrhythmogenic and negative effects inotoropnym. At the same time, the existence of such phenomena in humans has not been confirmed. In particular, Piccirillo et al., Surveying 10 patients with chronic heart failure due to dilated cardiomyopathy and 10 healthy volunteers showed no changes in QT interval after administration of sildenafil 50 mg. The authors concluded that sildenafil at therapeutic concentrations has no effect on myocardial repolarization. Tadalafil does not change the duration of the interval QT. At the same time, the use of vardenafil may be accompanied by a slight lengthening of the interval QT, in connection with what is not recommended to be considered in patients with extension of the indicator, as well as receiving antiarrhythmic drugs IA and III classes.

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Interesting results presented Ockaili et al. Researchers have demonstrated a reduction in the size of the zone of myocardial infarction in rabbits by intravenous injection of sildenafil. The authors found that this effect is eliminated by the introduction of 5-gidroksidekanoata, an inhibitor of mitochondrial ATP-sensitive potassium channels, allowing them to link the favorable effects of sildenafil with the action on these channels. However, the authors obtained results need confirmation.

Dominant form of PDE in the coronary arteries is PDE type 1, which provides between 73% to 80% of the total cGMP-hydrolyzing activity. This is confirmed by experimental studies do not show a significant effect of inhibition of PDE-5 on blood flow in coronary vessels.

The first information about the possible increased risk of myocardial infarction while taking sildenafil have caused the appearance of assumptions about the origin of the phenomenon of "coronary steal" in the action of the drug. Animal studies have not confirmed these hypotheses. Hermann et al. evaluate coronary blood flow in humans before and after administration of sildenafil with intracoronary Doppler. Sildenafil not only reduced blood flow in normal and stenosed vessels, but even increased functional reserve, the latter also occurred equally in normal and injured coronary artery atherosclerosis. Investigations of the PDE-5 inhibitors in the tolerance to physical load has not been shown to reduce the latter after taking the drugs. Moreover, some studies indicated even a slight improvement in tolerance to stress, which, however, should not be surprising, given the above background on the PDE-5 inhibitors.

Large-scale studies, as mentioned above, also showed no increase the likelihood of myocardial infarction, coronary heart disease (CHD) and sudden cardiac death while taking various inhibitors of PDE-5.

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Of particular interest is the effect of PDE-5 inhibitors on endothelial function of coronary arteries, but this will be discussed later.

Blood pressure in the pulmonary vessels of man depends on the activity of PDE 1,3,4 and 5 types. This has led to study the effect of PDE-5 inhibitors on hemodynamic parameters of pulmonary circulation.

In several pilot studies conducted on animals showed a decrease in pressure in the pulmonary trunk with the introduction of sildenafil. This fact has become a prerequisite for exploring the use of sildenafil in the treatment of pulmonary hypertension. Michelakis et al. investigated the effects of oral sildenafil in patients with severe primary and secondary pulmonary hypertension. The authors noted a significant reduction in pulmonary vascular resistance and a moderate increase in cardiac index. The combination of sildenafil with nitric oxide resulted in a potentiation of favorable effects. Wilkens et al. showed that the addition of sildenafil to iloprost in the treatment of patients with primary pulmonary hypertension accompanied by improved health status of patients. The possibility of using inhibitors of PDE-5 in the treatment of pulmonary hypertension of different origin is confirmed and a number of other works.

Effect of inhibitors of PDE-5 on blood pressure was studied in sufficient detail, as hypotension initially seen as the most dangerous side effect of this group of drugs, which, we recall, are among the vasodilators. Studies have shown that the use of inhibitors of the PDE-5 leads to a decrease in both systolic and diastolic blood pressure an average of not more than 10 mm Hg. Such fluctuations are very safe for most men, but in patients prone to hypotension, including in connection with the presence of aortic stenosis, are potentially hazardous, and therefore in these patients PDE-5 inhibitors should be used with caution.

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Clinically important is the influence of inhibitors of PDE type 5 on blood pressure in patients taking antihypertensive medications. First of all, it should be noted that the basic and common to all three PDE-5 inhibitors is contraindicated reception nitrate, which is associated with the possibility of severe hypotension as a consequence of potentiation of vasodilating effects. Vardenafil and tadalafil also should not assign patients receiving alpha-blockers, in connection with a high probability of dangerous hypotension. The exception is tamsulosin, which can be combined with tadalafilom. As sildenafil, its application in doses of 50 and 100 mg is contraindicated within 4 hours after administration of alpha-blockers. Patients treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers and calcium channel inhibitors, PDE-5 can be given without restrictions.

Currently, considerable research efforts aimed at studying the effect of inhibitors of the PDE-5 on endothelial function, especially in endothelial dysfunction. Given the importance of endothelial dysfunction in the pathogenesis of atherosclerosis and its complications, restoration of functional ability of the endothelium is a promising method of prevention and treatment of cardiovascular diseases.

As mentioned above, nitric oxide NO is the main vasodilator, allocated endothelium, and reduction of its synthesis and / or bioavailability is considered as the primary mechanism of endothelial dysfunction. Since PDE-5 inhibitor, increasing the concentration of cGMP, in fact exacerbated the effects of NO, their action may lead to endothelial dysfunction. It should also be noted that the effectiveness of PDE-5 inhibitors in the treatment of erection disorders is largely a consequence of the favorable effect on the function of endothelial tissue of the corpora cavernosa, a defeat which is an important pathophysiological mechanism for the development of most cases of organic erectile dysfunction.

The most well-studied is the effect on endothelial function of coronary and brachial arteries of the drug sildenafil, which is associated with its longer available for clinical use. The use of sildenafil in doses ranging from 25 to 100 mg was associated with improved endothelial function of brachial artery in patients with heart failure, diabetes mellitus (DM), coronary heart disease and smoking. The ability of sildenafil to eliminate smoking caused a brief deterioration of endothelial function. In studies of patients with heart failure, sildenafil, in addition to endothelial dysfunction in brachial and coronary arteries, also leads to improvement of pulmonary hemodynamics and provided a moderate antiplatelet effect. Combined method of sildenafil and the ACE inhibitor ramipril in this group of patients was accompanied by a potentiation of the favorable effect of both drugs on endothelial function.