iloprost and Nausea

The application of iloprost, a stable prostacyclin analogue, by inhalation has been shown to improve hemodynamic variables in patients with primary pulmonary hypertension. However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors.. The short-term effects of 8.4 to 10.5 microgram of aerosolized iloprost, the phosphodiesterase type 5 inhibitor sildenafil, and the combination thereof were compared in 5 patients with primary pulmonary hypertension. Aerosolized iloprost resulted in a more pronounced decrease in mean pulmonary arterial pressure (PAP) than sildenafil alone (9.4+/-1.3 versus 6.4+/-1.1 mm Hg; P<0.05). The reduction in mean PAP after sildenafil was maximal after the first dose (25 mg). The combination of sildenafil plus iloprost lowered mean PAP significantly more than iloprost alone (13.8+/-1.4 versus 9.4+/-1.3 mm Hg; P<0.009). No significant changes in heart rate or systemic arterial pressure were observed during any treatment. The treatments were well tolerated, without major adverse effects.. Sildenafil caused a long-lasting reduction in mean PAP and pulmonary vascular resistance, with a further additional improvement after iloprost inhalation. These data suggest that small doses of a phosphodiesterase type 5 inhibitor may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension.

Topics: Administration, Inhalation; Administration, Oral; Blood Pressure; Cardiac Output; Cough; Drug Therapy, Combination; Female; Headache; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Nausea; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vascular Resistance; Vasodilator Agents

To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma).. A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary.. Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058).. Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Data Interpretation, Statistical; Double-Blind Method; Female; Headache; Humans; Iloprost; Male; Middle Aged; Nausea; Placebos; Raynaud Disease; Recurrence; Scleroderma, Systemic; Time Factors; Treatment Outcome; Vasodilation; Vasodilator Agents

To assess efficacy and tolerability of two dosages of the oral prostacyclin analogue iloprost versus placebo in thromboangiitis obliterans (TAO).. Placebo-controlled, double-blind, study; TAO patients randomised to iloprost 100, 200 micrograms, or placebo bid for 8 weeks, with 6 months' follow-up.. Three-hundred and nineteen TAO patients with rest pain, trophic lesions (or both) from 23 clinics in six European countries. Primary endpoint: total healing of most important lesion. Secondary endpoint: relief of rest pain without need of analgesics. Combined endpoint: alive without major amputation, no lesions, no rest pain, no use of analgesics.. Total healing of lesions was not significantly different between treatment groups at any time point. For relief of rest pain without need of analgesics, low dose (LD) iloprost was significantly more effective than placebo at end of follow-up (placebo 49%; LD iloprost 63%; p = 0.020). This also applied to the combined endpoint (placebo 35%; LD iloprost 50%; p = 0.016). High dose iloprost (HD) failed to show significant treatment effects over placebo.. Iloprost LD was significantly more effective than placebo for relief of rest pain without need of analgesics and for a combined endpoint at 6 months of follow-up, whilst both iloprost doses showed no significant effects vs. placebo on total healing of lesions.

Topics: Administration, Oral; Adult; Double-Blind Method; Female; Follow-Up Studies; Headache; Humans; Iloprost; Male; Middle Aged; Nausea; Pain Measurement; Patient Compliance; Thromboangiitis Obliterans; Treatment Outcome; Vasodilator Agents

To assess the effectiveness of ondansetron in relieving symptoms of nausea and vomiting which were refractory to metoclopramide and cyclizine, in a patient receiving iloprost infusions.. Case observation in a series of 7 infusions.. Ondansetron reduced WHO symptom scores of vomiting from Grade 2 to Grade 0. Symptoms of nausea were abolished on some occasions.. Ondansetron was found to be effective at abolishing symptoms of vomiting and partially effective against symptoms of nausea. It may prove to be a useful treatment modality to allow the patient to tolerate further infusions of iloprost where nausea and vomiting has failed to respond to other agents.

Topics: Aged; Antiemetics; Humans; Iloprost; Infusions, Intravenous; Male; Metoclopramide; Nausea; Ondansetron; Platelet Aggregation Inhibitors; Vomiting

Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.

Topics: Adult; Blood Pressure; Blood Viscosity; Cardiovascular Agents; Epoprostenol; Erythrocytes; Headache; Heart Rate; Hemodynamics; Humans; Iloprost; Male; Nausea; Platelet Aggregation; Platelet Count; Pulse; Time Factors