sildenafil-citrate and isosorbide-5-mononitrate

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adrenergic alpha-Antagonists; Arteriosclerosis; Blood Pressure; Carbolines; Contraindications; Coronary Disease; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Interactions; Endothelium, Vascular; Erectile Dysfunction; Heart Rate; Humans; Hypotension; Imidazoles; Isosorbide Dinitrate; Male; Molecular Structure; Myocardial Infarction; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilation; Vasodilator Agents

NO donor drugs (eg, isosorbide mononitrate; ISMN) and phosphodiesterase 5 inhibitors (eg, sildenafil) have antihypertensive properties, and the combination can markedly reduce blood pressure (BP). The objective of this "proof-of-concept" study was to investigate the effect on BP of a combination of single oral doses of sildenafil (50 mg) and ISMN (10 mg) in patients with treatment-resistant hypertension. Six subjects with treatment-resistant hypertension were included, and their usual antihypertensive medication was continued during the study. Sildenafil alone, ISMN alone, and the combination all reduced brachial and central aortic BPs compared with placebo. The combination of sildenafil and ISMN produced the largest fall in BP (maximum brachial BP reduction of 26/18 mm Hg compared with placebo), without producing significant adverse effects. ISMN, alone and in combination with sildenafil, also reduced arterial wave reflection and central BP. In summary, in patients with treatment-resistant hypertension maintained on their usual antihypertensive treatment, sildenafil given alone and ISMN given alone both acutely reduced BP. There was additional BP reduction when these drugs were given in combination. In this therapeutically challenging group of patients, the combination of an NO donor drug and a phosphodiesterase 5 inhibitor may represent an effective treatment. Longer studies in larger numbers of patients are now justified.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypertension; Isosorbide Dinitrate; Male; Middle Aged; Nitric Oxide Donors; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome

Mild hemodynamic effects have been reported with sildenafil citrate therapy.. To compare the hemodynamic effects of sildenafil and isosorbide mononitrate (ISMN) in men with coronary artery disease and erectile dysfunction.. A total of 31 men aged 35 years or older with coronary artery disease (at least 50% narrowing of the left main stem or at least 70% narrowing of any other coronary artery) and erectile dysfunction (receiving medication for erectile dysfunction or scoring less than 26 out of a maximum score of 30 on the erectile function domain questions of International Index of Erectile Function) were randomized to sildenafil 100 mg (n = 10), ISMN 40 mg (n = 11), or placebo (n = 10) in this single-dose multicenter study.. Hemodynamic parameters were measured at baseline, 1, 2, 4, and 6 hours post dose.. Compared with baseline, cardiac index increased slightly with sildenafil (0.29 L/min/m2 at 1 hour) and decreased slightly with placebo (-0.12 L/min/m2 at 4 hours) and ISMN (-0.14 L/min/m2 at 1 hour). The stroke volume index increased from baseline at each time point post dose with sildenafil (4.4 mL/m2 at 2 hours), but decreased with ISMN (-5.8 mL/m2 at 1 hour) and placebo (-2.8 mL/m2 at 4 hours). ISMN reduced mean arterial pressure more than sildenafil did (-22 vs. -10 mm Hg at 2 hours, respectively). Both sildenafil and ISMN increased heart rate (4 vs. 7 beats/minute at 1 hour, respectively) and decreased systemic vascular resistance, but sildenafil produced greater reductions in pulmonary vascular resistance. There were no serious adverse events in the sildenafil group.. Sildenafil 100 mg was well tolerated and induced smaller changes in central and peripheral hemodynamic pressures compared with ISMN 40 mg. Moreover, sildenafil selectively reduced pulmonary resistance, which may have clinical importance in pulmonary hypertension.

Topics: Adult; Coronary Artery Disease; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Hemodynamics; Humans; Isosorbide Dinitrate; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

We sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina.. Sildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs.. Two double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 microg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug.. The effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, -52/-29 mm Hg) were greater than the effects of placebo plus ISMN on BP (-25/-15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (-36/-21 mm Hg) compared with placebo plus GTN (-26/-12 mm Hg; p < 0.01).. Coadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Aged; Angina Pectoris; Blood Pressure; Contraindications; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Humans; Isosorbide Dinitrate; Male; Middle Aged; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Focal hepatic venous outflow obstruction frequently occurs after extended liver resection and leads to a portal hypertension, arterial hypoperfusion and parenchymal necrosis. In this study, we investigated the pharmacological modulation of liver perfusion and hepatic damage in a surgical model of hepatic outflow obstruction after extended liver resection by administration of 5 different drugs in comparison to an operative intervention, splenectomy.. Carvedilol and ISMN significantly decreased the portal pressure in normal non-operated rats from 11,1 ± 1,1 mmHg (normal rats) to 8,4 ± 0,3 mmHg (carvedilol) respectively 7,4 ± 1,8 mmHg (ISMN). ISMN substantially reduced surgery-induced portal hypertension from 15,4 ± 4,4 mmHg to 9,6 ± 2,3 mmHg. Only splenectomy reduced the portal flow immediately after operation by approximately 25%. No treatment had an immediate effect on the hepatic arterial perfusion. In all treatment groups, portal flow increased by approximately 3-fold within 24 h after operation, whereas hepatic arterial flow decreased substantially. Neither treatment reduced hepatic damage as assessed 24 h after operation. The distribution of proliferating cells appeared very similar in all drug treated groups and the splenectomy group.. Transient relative reduction of portal pressure did not result in a reduction of hepatic damage. This might be explained by the development of portal hyperperfusion which was accompanied by arterial hypoperfusion.

Topics: Animals; Antihypertensive Agents; Carbazoles; Carvedilol; Hepatectomy; Isosorbide Dinitrate; Liver; Lypressin; Male; Octreotide; Portal Pressure; Propanolamines; Rats, Inbred Lew; Sildenafil Citrate; Splenectomy; Terlipressin; Vasoconstrictor Agents; Vasodilator Agents