Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension.

Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Primary pulmonary hypertension is a rare disease of childhood, which carries a poor prognosis. Patients often present with severe exercise limitation, and untreated life expectancy is less than 1 year. Pharmacological intervention is directed towards reduction of the raised pulmonary artery pressure with vasodilator treatment, initially with calcium antagonists, although more recently long term prostacyclin treatment has shown benefit in some patients. Heart-lung transplantation remains an option for children with severe disease refractory to therapeutic treatment. A 4 year old Bangladeshi girl with dyspnoea, cyanosis, and signs of a low cardiac output, is described. Initial treatment with prostacyclin was gradually reduced, and maintenance treatment with oral sildenafil (Viagra; Pfizer) instituted. At follow up 3 months later, her exercise capacity was greatly improved and she continues to enjoy a good quality of life without obvious side effects. In view of the encouraging initial results, this may become an acceptable adjunct in treating this patient group. Journal ISSN: 1468-201X Issue: 84-2 (2000) Pages: E4

Penile erection and cardiac risk: pathophysiologic and pharmacologic mechanisms.
Penile erection and cardiac risk: pathophysiologic and pharmacologic mechanisms. Erection is initiated through the parasympathetic nervous system, activation of which overrides the sympathetic tone that maintains the penis in a nonerectile (flaccid) state. This state is maintained mainly through the release of norepinephrine from penile adrenergic nerves. Norepinephrine contracts the vasculature and cavernosal smooth muscle. Arousal/erection is associated with a decrease of norepinephrine release in the penis, with a release of nitric oxide, and with a reduction in penile smooth muscle tone. It is also associated with minor cardiovascular changes. Heart rate increases by 4-8 beats per minute, on average, and the rate-pressure product and oxygen consumption increase by approximately 25%. There may be no changes in systemic venous norepinephrine concentrations; systemic venous epinephrine concentrations increase by about 60%. Drugs initiating or enhancing erection act by inhibiting norepinephrine-induced contraction (e.g., phentolamine) or by enhancing or directly inducing relaxation of the corpora cavernosa and the penile vasculature (e.g., sildenafil). Despite potentially negative hemodynamic actions when given parenterally, oral phentolamine-in doses required for enhancing erection-appears to produce few cardiovascular adverse effects. The hemodynamic effects of sildenafil are small, even in patients with coronary artery disease. However, the effects of the drug on human myocardium have not been conclusively established, and should be further investigated. As judged by available information, the cardiac risk associated with erection, with or without enhancement of drugs currently used for treatment of erectile dysfunction, is low. Journal ISSN: 0002-9149 Issue: 86-2A (2000) Pages: 23F-26F

Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study.
Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study. BACKGROUND: Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12-79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. RESULTS: Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. CONCLUSIONS: Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period. Journal ISSN: 0011-9059 Issue: 40-1 (2001) Pages: 72-6

Sexual intercourse and stable angina pectoris.
Sexual intercourse and stable angina pectoris. Stable angina pectoris is a common condition associated with chest pain predictable for a given level of exercise. Sexual intercourse does not lead to exaggerated heart rate or blood pressure responses and is interpreted by the heart as one of many forms of activity that may take place in a 24-hour period. Stable angina patients optimally treated are not at significantly increased cardiovascular risk during sexual intercourse. Erectile dysfunction (ED) increases with age and shares similar cardiovascular risk factors with stable angina. Sildenafil citrate can be safely prescribed for stable patients with ED providing they are not taking oral, topical, or sublingual nitrates. Sexual relationships should not be constrained by the diagnosis of angina pectoris provided appropriate medical advice is given on risk status. Family physicians and specialists are able to provide this advice based on their knowledge of the patient and the social circumstances. Impersonal advice is potentially dangerous and should be vigorously discouraged. Journal ISSN: 0002-9149 Issue: 86-2A (2000) Pages: 35F-37F

Cardiovascular risk and sildenafil.
Cardiovascular risk and sildenafil. Sildenafil citrate is the first oral agent approved for the treatment of erectile dysfunction (ED); other oral agents are in the process of development. Because the mechanism of action of many of these agents involves vasodilation, there is a potential for interaction with the cardiovascular system. Sildenafil inhibits phosphodiesterase-5 (PDE-5) which is found in the corpus cavernosum and in the systemic vasculature. Sildenafil causes a mild decrease in systemic arterial pressure ( approximately -8/-5.5 mm Hg); it causes a synergistic and often major decrease in systemic arterial pressure in the presence of organic nitrates (nitric oxide donors). Sildenafil is therefore contraindicated in patients taking organic nitrates. A review was made of clinical trials in populations of men with (1) erectile dysfunction; (2) chronic stable ischemic heart disease and erectile dysfunction; and (3) hypertension and erectile dysfunction. This review showed that sildenafil was effective and not associated with an increase in serious cardiovascular adverse events, myocardial infarction (MI), or death compared with placebo. Although there have been spontaneous reports of death among men using sildenafil, there are limitations to spontaneous-event reporting. In addition. the numbers of such reports are well below the expected numbers of deaths when considering the number of men who have received prescriptions for sildenafil and their age and cardiovascular risk factor profile. Because there is a small but finite risk of having a cardiac event with sexual activity, physicians should discuss with their cardiac patients the risks of sexual activity before prescribing any treatment for ED. In addition, they should evaluate their patients@apos; cardiac status when considering the safety of administering any ED treatment that may have systemic vasodilatory properties and can potentially lower blood pressure. In some cases, exercise treadmill testing may be warranted to determine whether ED patients with coronary artery disease can achieve the physiologic workload (4-6 metabolic equivalents) associated with sexual intercourse. Journal ISSN: 0002-9149 Issue: 86-2A (2000) Pages: 57F-61F