Dipyridamole treatment in chronic obstructive airways disease: Effect on platelet regeneration time

Tremoli, Elena; L, Bertoli; Merlini, R; Colli, S.; Maderna, P.; Mantero, O; Sirtori, C.R.

doi:10.1007/bf00605992

Cited by 3 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our working hypothesis was based on the following sequence of events: Chronic hypoxemia and pulmonary hypertension were inclusion criteria for this study, while platelet activation was as sumed to be present from the results of previous studies [4,6,7]. An accelerated platelet turnover in patients with COPD was first reported by Steele et al [4], who observed a shortening of platelet survival time in 95% of their patients with hypox emia.…”

Section: Discussionmentioning

confidence: 97%

“…Unlike other platelet inhibitors, dipyridamole does not block, but may even enhance the activity of prostacyclin [8], a powerful antiaggre gating and pulmonary vasodilating agent produced by lung endothelial cells in large quantities in response to hypoxia [9]. Moreover, the drug prevents hypoxic pul monary vasoconstriction in experimental models [5,10], while in patients with COPD it is an effective inhibitor of plate let activation [6,7,11], We report the re sults of a pilot study aimed at evaluating whether prolonged treatment with dipyr idamole might have beneficial effects of the hypoxemic pulmonary hypertension of COPD patients.…”

Section: Introductionmentioning

confidence: 99%

“…the alterations of the pulmo nary vasculature induced by chronic hy poxemia and hypertension, may be re sponsible for increased platelet-vessel wall interactions at the sites of endothelial cell injury in patients with COPD. These pa tients have indeed shortened platelet sur vival [5] and regeneration [6] times and raised plasma levels of p-thromboglobulin [7], a specific protein secreted by stimu lated platelets. For these reasons, we tested the hypothesis that platelet activation in hibitors could be effective in lowering the hypoxemia-induced increase in pulmo nary vascular resistance.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Dipyridamole on the Hypoxemic Pulmonary Hypertension of Patients with Chronic Obstructive Pulmonary Disease

Nenci¹,

Berrettini²,

Todisco³

et al. 1988

Respiration

View full text Add to dashboard Cite

Based on the hypothesis that blood platelets contribute to the pathogenesis of hypoxemic pulmonary hypertension in patients with chronic obstructive pulmonary disease (COPD), the effect of a prolonged treatment with dipyridamole, a platelet-inhibiting drug, on hypoxemic pulmonary hypertension was evaluated in a double-blind cross-over study. Eight patients with COPD, pulmonary hypertension [mean systolic pressure 52.2 ± (SD) 9.7 mm Hg; mean diastolic pressure 25.8 ± (SD) 6.8 mm Hg] and shortened platelet regeneration time [mean 5.2 ± (SD) 1.2 days] received, in a cross-over random sequence, the following two 3-month treatments: (a) dipyridamole 100 mg and acetylcysteine 100 mg every 6 h; (b) acetylcysteine, 100 mg every 6 h. Dipyridamole significantly prolonged the platelet regeneration time [mean 6.5 ± (SD) 1.0 days; p < 0.05]. There was no significant effect on diastolic pulmonary pressure. However, systolic pressure was significantly (p < 0.05) lower after dipyridamole [46.8 ± (SD) 16 mm Hg] than after placebo [56.1 ± (SD) 14 mm Hg]. These results suggest that dipyridamole can slow the progression of hypoxemic pulmonary hypertension in patients with COPD.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Dipyridamole on the Hypoxemic Pulmonary Hypertension of Patients with Chronic Obstructive Pulmonary Disease

Nenci¹,

Berrettini²,

Todisco³

et al. 1988

Respiration

View full text Add to dashboard Cite

show abstract

“…Theophylline at therapeutic concentrations antagonizes adenosine receptors (12,13); it should therefore be used with caution in patients treated with dipyridamole (33,34), when looking for a maximal antiplatelet effect.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity

et al. 1986

View full text Add to dashboard Cite

SummaryDipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5’-deoxy-5’-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness.Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.

show abstract

Dipyridamole: A Critical Evaluation

Rivey¹,

Alexander²,

Taylor³

1984

Drug Intelligence & Clinical Pharmacy

View full text Add to dashboard Cite

Dipyridamole is a vasodilator that is used primarily in clinical practice as an anti platelet agent. It increases coronary blood flow and was originally introduced as an antianginal agent. An ability to prolong a shortened platelet survival has been used to justify its value in preventing thromboembolic complications. Conditions characterized by a reduction in platelet survival and where dipyridamole has been used include heart valve replacement, arterial grafting, cerebrovascular disorders, and disorders of peripheral circulation. The in vivo effect of dipyridamole on platelet aggregation has not been well defined and may depend on additional factors. Prostaglandins appear to have important roles in platelet homeostasis; their relationships to the action of dipyridamole are discussed. Dipyridamole usually is combined with aspirin for synergistic anti-aggregatory purposes. However, the nature of the interaction has not been elucidated and benefit from the addition of dipyridamole has not been demonstrated in clinical studies. A review of clinical studies using dipyridamole indicates that it currently has limited value. DIPYRIDAMOLE, a pyrimidopyrimidine compound, was marketed originally in the U.S. in 1959 as a coronary vasodilator. 1 Recognition of its ability to modify platelet function followed a short time later." It has been used to treat patients with coronary artery disease, myocardial infarction, prosthetic heart valve replacement, coronary and lower extremity arterial bypass grafting, neurological diseases, disorders of peripheral circulation, and as a diagnostic adjunct for myocardial imaging. Despite extensive use, results of clinical studies have failed to substantiate the claimed benefits of dipyridamole in many instances. It is the purpose of this article to review and evaluate data concerning the pharmacology, pharmacokinetics, and clinical efficacy of this agent.

show abstract

Dipyridamole treatment in chronic obstructive airways disease: Effect on platelet regeneration time

Cited by 3 publications

References 17 publications

Effects of Dipyridamole on the Hypoxemic Pulmonary Hypertension of Patients with Chronic Obstructive Pulmonary Disease

Effects of Dipyridamole on the Hypoxemic Pulmonary Hypertension of Patients with Chronic Obstructive Pulmonary Disease

Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity

Dipyridamole: A Critical Evaluation

Contact Info

Product

Resources

About