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Biomedical subjects

Graham Jackson

Publications and source records attributed to Graham Jackson.

At least 73 records · Page 4Linked to original sources
PubMed2004

Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men.

PURPOSE: Tadalafil, a phosphodiesterase type 5 inhibitor, is effective therapy for erectile dysfunction (ED). Men with ED have a high incidence of comorbid conditions including cardiovascular disease, diabetes mellitus and benign prostatic hyperplasia. Although phosphodiesterase type 5 inhibitors are safe when administered with most medications, sildenafil given with doxazosin and vardenafil given with terazosin evoke orthostatic hypotension in some patients. We examined the hemodynamic interactions of tadalafil with the alpha-blockers doxazosin and tamsulosin. MATERIALS AND METHODS: In separate double-blind, placebo controlled, randomized crossover studies (18 patients in each study) we evaluated the hemodynamic effects of doxazosin 8 mg with tadalafil 20 mg, and tamsulosin 0.4 mg with tadalafil 10 and 20 mg. Blood pressure (BP) and heart rate were recorded before dosing and for 24 hours after dosing. RESULTS: Tadalafil 20 mg augmented the hypotensive effect of doxazosin by producing a mean maximal decrease in standing systolic BP (SBP) that was significantly greater than placebo (a mean difference of 9.8 mm Hg). Analysis of BP outliers showed that the number of subjects with a standing SBP of less than 85 mm Hg was greater after doxazosin plus tadalafil (28%) versus doxazosin plus placebo (6%). In subjects on tamsulosin, tadalafil 10 and 20 mg produced mean maximal decreases in standing SBP that were similar to placebo (mean difference of 1.7 and 2.3 mm Hg, respectively). No subject taking tamsulosin had a decrease in standing SBP less than 85 mm Hg. CONCLUSIONS: Tadalafil augmented the hypotensive effects of doxazosin but had little hemodynamic interaction with tamsulosin. In patients taking tadalafil for ED, tamsulosin 0.4 mg may be given for the treatment of benign prostatic hyperplasia.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Smoking politics.

Explore the source record for details and available documents.

Health Care Costs↗
PubMed2004

Diabetic and hypertension guidelines updated.

The guidelines are clear. We need optimal control of blood pressure and lipid profiles. Diabetics need particular aggressive risk reduction. No risk factor should be managed in isolation--overall risk reduction is essential. We have a job to do and must do it thoroughly--we now need a programme of early detection and that needs political will and investment.

Diabetes Mellitus↗
PubMed2004

Pharmacotherapy for erectile dysfunction.

INTRODUCTION: Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction. METHODS: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation. CONCLUSIONS: There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.

Apomorphine↗
PubMed2004

Update on clinical trials of tadalafil demonstrates no increased risk of cardiovascular adverse events.

INTRODUCTION: Cardiovascular disease and erectile dysfunction (ED) share similar risk factors and often occur concomitantly. Therefore, men with ED may be at increased risk for cardiovascular adverse events. AIM: The aim of this retrospective analysis was to evaluate the cardiovascular adverse events in clinical trials of tadalafil, an effective medication for the treatment of ED. METHODS: An integrated analysis of cardiovascular adverse events was performed on a database from 35 controlled clinical trials (placebo [N = 2,118] and tadalafil [N = 5,228]) and eight open-label trials of tadalafil (tadalafil [N = 6,939]). Some patients in controlled trials also received tadalafil in the open-label extension phase of four trials. Across all trials, the dose range of tadalafil was 2-25 mg, with the majority of patients receiving tadalafil 20 mg. This analysis represents an update of previous published results. RESULTS: In 35 controlled tadalafil clinical trials, the incidence of cardiovascular adverse events was low and comparable in tadalafil- and placebo-treated patients. The rate of myocardial infarction (MI) across all controlled and open-label studies was 0.33 per 100 patient-years in tadalafil-treated patients (N = 10,460, patient exposure = 5,088 patient-years). The MI rate in tadalafil-treated patients was comparable to that in placebo-treated patients (0.41 per 100 patient-years; N = 2,118; 489 patient-years), and to that in an age-standardized male population (0.6 per 100 patient-years). The cardiac mortality rate in tadalafil-treated patients across all studies (N = 10,460) was 0.12 per 100 patient-years which was not increased compared with the cardiac mortality rate of 0.26 per 100 patient-years reported in an age-standardized male population. CONCLUSIONS: In tadalafil clinical trials, the incidence of cardiovascular adverse events in patients receiving tadalafil was low and comparable to placebo. Tadalafil did not increase the rate of MI or cardiac mortality compared with reported rates from epidemiological studies. This favorable cardiovascular safety profile for tadalafil is important, because men with ED commonly have cardiovascular disease and may seek medical therapy for ED.

Adult↗