Effects of intravenous infusion of prostacyclin (PGI2) in man

O’Grady, John; Warrington, Steve; Moti, MJ; Bunting, Stuart; Flower, Roderick J.; Fowle, A. S. E.; Higgs, E. A.; Moncada, Salvador

doi:10.1016/0090-6980(80)90030-1

Cited by 113 publications

(32 citation statements)

References 10 publications

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“…As in other studies with PGI2 involving normal volunteers, we found that headache was a common feature (Data et al, 1981;Eklund et al, 1981;FitzGerald et al, 1979;O'Grady et al, 1979O'Grady et al, , 1980Wilhelmsson et al, 1981). After flushing, this is usually the most frequent adverse effect in patient studies also (Bergman et al, 1981;Dowd et al, 1982;Olsson, 1980;Pardy et al, 1980;Szczeklik, et al, 1980a;Zusman et at., 1981b).…”

Section: Headachesupporting

confidence: 49%

“…Excessive restlessness and fidgeting, not necessarily associated with anxiety, is an unusual drug response and has been noted with PGI2 right from the earliest studies (Szczeklik et al, 1978a;FitzGerald et al, 1979;O'Grady et al, 1980;Chierchia et al, 1979;Olsson, 1980: Guadagni et al, 1981Data et al, 1981;Hensby etal., 1979). The mechanism is unknown.…”

Section: Restlessnessiuneasementioning

confidence: 99%

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Side effects occurring during administration of epoprostenol (prostacyclin, PGI2), in man.

Pickles¹,

O’Grady²

1982

Brit J Clinical Pharma

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1 Fifty infusions of epoprostenol (PGI2) were made, usually increasing the infusion rate until adverse effects were encountered. The volunteers were appraised that they might experience headache and facial flushing. 2 Facial flushing, headache, tachycardia and decrease in diastolic blood pressure were seen in almost all subjects. Erythema over the venous infusing site was also encountered in 13 infusions. Less common effects were sudden bradycardia, pallor and sweating-the vagal reflex-(seven times) and chest pain (twice). Other complaints included restlessness, abdominal discomfort, nausea and drowsiness.3 The literature on side effects reported during PGI2 infusion is reviewed and recommendations are made concerning administration of PGI2.

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Section: Headachesupporting

confidence: 49%

Section: Restlessnessiuneasementioning

confidence: 99%

Side effects occurring during administration of epoprostenol (prostacyclin, PGI2), in man.

Pickles¹,

O’Grady²

1982

Brit J Clinical Pharma

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“…Pulmonary hypertension is associated with vasoconstriction, thrombosis and proliferation, and this may be partly due to a lack of endogenous prostacyclin [1] secondary to prostacyclin synthase downregulation [2]. This supports a strong rationale for prostanoid use as therapy for the disease, with the first experiences in pulmonary hypertension patients published in 1980 [3], and the first patient with severe idiopathic pulmonary arterial hypertension (iPAH) to receive long-term therapy in 1984 [4]. After 25 yrs of continued knowledge, prostanoids remain a mainstay in the treatment of these patients.…”

mentioning

confidence: 63%

Prostacyclin therapies for the treatment of pulmonary arterial hypertension

Gomberg‐Maitland¹,

Olschewski²

2008

Eur Respir J

262

181

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Prostacyclin and its analogues (prostanoids) are potent vasodilators and possess antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary hypertension (PH) is associated with vasoconstriction, thrombosis and proliferation, and the lack of endogenous prostacyclin may considerably contribute to this condition. This supports a strong rationale for prostanoid use as therapy for this disease. The first experiences of prostanoid therapy in PH patients were published in 1980.Epoprostenol, a synthetic analogue of prostacyclin, and the chemically stable analogues iloprost, beraprost and treprostinil were tested in randomised controlled trials. The biological actions are mainly mediated by activation of specific receptors of the target cells; however, new data suggest effects on additional intracellular pathways. In the USA and some European countries, intravenous infusion of epoprostenol and treprostinil, as well as subcutaneous infusion of treprostinil and inhalation of iloprost, have been approved for therapy of pulmonary arterial hypertension. Iloprost infusion and beraprost tablets have been approved in few other countries. Ongoing clinical studies investigate oral treprostinil, inhaled treprostinil and the combination of inhaled iloprost and sildenafil in pulmonary arterial hypertension. Combination of other targeted therapies with prostanoids appears to be effective and safe.After 25 yrs of continued knowledge, prostanoids remain a mainstay in the treatment of pulmonary arterial hypertension.

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“…This compound is rapidly hydrolysed in whole blood and plasma with a half-life of around 6 min (Orchard & Robinson, 1981). In man, the onset and offset of the cardiovascular actions of prostacyclin are rapid, less than 5 min, which means that its effects can be easily reversed (O'Grady et al, 1980;Lewis & Dollery, 1983 …”

mentioning

confidence: 99%

Modification of the 31P magnetic resonance spectra of a rat tumour using vasodilators and its relationship to hypotension

Tozer

Maxwell²,

Griffiths³

et al. 1990

Br J Cancer

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Summary The effects of different doses of hydralazine and prostacyclin on the 31P magnetic resonance spectra of the LBDS, fibrosarcoma were investigated and related to their effects on mean arterial blood pressure (MABP) and heart rate. The effect of reducing MABP by bleeding the animals, via the tail artery, was also investigated. Tumour spectral changes following high dose drug treatment (an (Hahn, 1974;Overgaard & Bichel, 1977;Overgaard & Nielsen, 1980). Hydralazine has also been shown to potentiate the cytotoxicity in solid rodent tumours in vivo of the bioreductive drugs RSU-1069(Chaplin & Acker, 1987 and SR4233 (Brown, 1987). These drugs are cytotoxic to hypoxic cells and their potentiation by hydralazine is presumably brought about by induced hypoxia secondary to a decrease in tumour blood flow.Selective reduction of tumour blood flow also has potential in more conventional chemotherapy. Stratford et al. (1987) showed that a carefully timed administration of hydralazine could increase the cytotoxic action of melphalan in transplanted rodent tumours whilst normal tissue toxicity remained unaffected. This could be explained by a hydralazine-induced selective reduction in tumour blood flow leading to entrapment of melphalan in the tumour tissue.Hydralazine is used clinically to control hypertension. Its plasma half-life in man is less than 60 min (Shepherd et al., 1980), but its half-life in vascular smooth muscle may be as high as 30 h (Gross, 1977) which is a possible disadvantage for application in tumour therapy. Horsman et al. (1989) have shown that, in mice, the mean arterial blood pressure, which falls on administration of hydralazine, has not returned to normal 8 h after injection. Tumour blood flow was not measured directly but there was also some indication that it too had not returned to pre-drug levels by 8 h. Any longterm reduction in the tumour blood supply would be a disadvantage for radiotherapy. Therefore, in the present study, the effect of hydralazine on cardiovascular parameters and tumour energy metabolism was compared with that of prostacyclin, an endogenous vasodilator formed from arachidonic acid (Moncada et al., 1976). This compound is rapidly hydrolysed in whole blood and plasma with a half-life of around 6 min (Orchard & Robinson, 1981). In man, the onset and offset of the cardiovascular actions of prostacyclin are rapid, less than 5 min, which means that its effects can be easily reversed (O'Grady et al., 1980;Lewis & Dollery, 1983

show abstract

Effects of intravenous infusion of prostacyclin (PGI2) in man

Cited by 113 publications

References 10 publications

Side effects occurring during administration of epoprostenol (prostacyclin, PGI2), in man.

Side effects occurring during administration of epoprostenol (prostacyclin, PGI2), in man.

Prostacyclin therapies for the treatment of pulmonary arterial hypertension

Modification of the 31P magnetic resonance spectra of a rat tumour using vasodilators and its relationship to hypotension

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