Pharmacology of bipyridine phosphodiesterase III inhibitors

Honerjäger, P

doi:10.1016/0002-8703(91)90828-6

Cited by 68 publications

(36 citation statements)

References 45 publications

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“…It selectively inhibits cAMP-specific phosphodiesterase III isoenzyme in the cardiac and vascular muscle [14]. Vasodilatation occurs due to an increase in cAMP levels in the smooth muscle, facilitating calcium uptake into the sarcoplasmatic reticulum, reducing the amount of calcium available for contraction and thereby reducing vascular tone [14,101]. Milrinone has a half-life of approximately 50 min [14].…”

Section: Endovascular Therapy In Sah-induced Cerebral Vasospasmmentioning

confidence: 99%

Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature

2013

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Objectives: Cerebral vasospasm is one of the leading causes of morbi-mortality following aneurysmal subarachnoid hemorrhage. The aim of this article is to discuss the current status of vasospasm therapy with emphasis on endovascular treatment. Methods: A comprehensive review of the literature obtained by a PubMed search. The most relevant articles related to medical, endovascular and alternative therapies were selected for discussion. Results: Current accepted medical options include the oral nimodipine and ‘triple-H' therapy (hypertension, hypervolemia and hemodilution). Nimodipine remains the only modality proven to reduce the incidence of infarction. Although widely used, ‘triple-H' therapy has not been demonstrated to significantly change overall outcome after cerebral vasospasm. Indeed, both induced hypervolemia and hemodilution may have deleterious effects, and more recent physiologic data favor normovolemia with induced hypertension or optimization of cardiac output. Endovascular options include percutaneous transluminal balloon angioplasty (PTA) and intra-arterial (IA) infusion of vasodilators. Multiple case reports and case series have been encountered in the literature using different drug regimens with diverse mechanisms of action. Compared with PTA, IA drug infusion has the advantages of distal penetration and a better safety profile. Its main disadvantages are the more frequent need for repeat treatments and its systemic hemodynamic repercussions. Alternative options using intraventricular/cisternal drug therapy and flow augmentation strategies have also shown possible benefits; however, their use is not yet as well established. Conclusion: Blood pressure or cardiac output optimization should be the mainstay of hyperdynamic therapy. Endovascular treatment appears to have a positive impact on neurological outcome compared with the natural history of the disease. The role of intraventricular therapy and flow augmentation strategies in association with medical and endovascular treatment may, in the future, play a growing role in the management of patients with severe refractory vasospasm.

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Section: Endovascular Therapy In Sah-induced Cerebral Vasospasmmentioning

confidence: 99%

Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature

2013

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“…2) Phosphodiesterase type III (PDE III) inhibitors like milrinone are used in acute or chronic heart failure for their positive inotropic, lusitropic, and vasodilator eŠects. 3,4) Positive inotropic eŠects in addition to a combined decrease in after-and preload is are why myocardial oxygen consumption does not increase. 2,3) Ventricularˆlling is better even at high heart rates due to their beneˆcial eŠects on diastolic heart function and thus results in better coronary perfusion.…”

Section: Introductionmentioning

confidence: 99%

“…3,4) Positive inotropic eŠects in addition to a combined decrease in after-and preload is are why myocardial oxygen consumption does not increase. 2,3) Ventricularˆlling is better even at high heart rates due to their beneˆcial eŠects on diastolic heart function and thus results in better coronary perfusion. 2,3) Milrinone also has direct vasodilatory eŠects on coronary arteries, lowering coronary arterial resistance by 30-40％.…”

Section: Introductionmentioning

confidence: 99%

“…2,3) Ventricularˆlling is better even at high heart rates due to their beneˆcial eŠects on diastolic heart function and thus results in better coronary perfusion. 2,3) Milrinone also has direct vasodilatory eŠects on coronary arteries, lowering coronary arterial resistance by 30-40％. 5,6) During CPB and in the reperfusion period, increased levels of cytokines such as tumor necrosis factor (TNF) were reported to be a result of myocardial stunning, respiratory distress syndromes, renal failure, pancreatitis, or neurologic syndromes.…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10][11] This may be partly due to milrinone's inhibitory eŠects on phagocytotic and adherence activities of leukocytes. 3) Bronchial smooth muscle relaxation by milrinone is beneˆcial to avoid bronchoconstrictive states induced by the in‰amma-tory response.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Low-dose Milrinone on Weaning from Cardiopulmonary Bypass and after in Patients with Mitral Stenosis and Pulmonary Hypertension

Öztekin

Yazici²,

Öztekin

et al. 2007

YAKUGAKU ZASSHI

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The phosphodiesterase inhibitor milrinone is usually preferred in patients with pulmonary hypertension and myocardial dysfunction after cardiopulmonary bypass. We investigated the eŠects of low-dose milrinone on pulmonary hypertension in the immediate pre-and postoperative period. Forty-seven patients were randomized to the control and milrinone groups. All patients had mean pulmonary artery pressure greater than 30 mmHg and pulmonary capillary wedge pressure greater than 20 mmHg and were candidates for mitral valve replacement for rheumatic mitral stenosis. Twenty-four patients received a loading dose of milrinone 25 mg/kg -1 during weaning from cardiopulmonary bypass, followed by a maintenance dose of 0.25 mg/kg -1 /min -1 to the end of the surgery. Cardiac output and other hemodynamic variables were noted at induction, weaning from bypass, and postoperative 1 h. Pulmonary artery pressure, capillary wedge pressure, and central venous pressure were signiˆcantly lower in the milrinone group during weaning after cardiopulmonary bypass, while other variables were roughly similar. However, patients in the control group required higher doses of vasodilators, inotropes, and antiarrhythmic agents. Mean arterial pressure in the milrinone group was signiˆcantly lower at 1 h postoperatively than in the control group; however, the patients did not need many more vasopressors. Fluid restriction and diuretic agent use were more signiˆcant in the control group. Systemic arterial hypotension and vasopressor requirements with milrinone use at inotropic doses were not observed at the doses used for the study. A total of 21.7％ of the patients in the control group required vasopressors in the perioperative period. Both groups demonstrated similar hematologic variables except that the hemoglobin level in the control group was signiˆcant-ly lower during postoperative days 1 and 7. Low-dose milrinone for a short-term during weaning from cardiopulmonary bypass may be used in patients with mitral stenosis and pulmonary hypertension for its eŠects on pulmonary artery pressures, less inotropic and vasopressor requirements, and ‰uid balance.

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Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents

Hornik

Yogev

Mourani

et al. 2019

The Journal of Clinical Pharma

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Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction of critical illness. We developed a population pharmacokinetic model of milrinone using nonlinear mixed‐effects modeling in NONMEM to perform dose‐exposure simulations in children with variable renal function. We included children aged <21 years who received intravenous milrinone per clinical care. Plasma milrinone concentrations were measured using a validated liquid chromatography–tandem mass spectrometry assay (range 1‐5000 ng/mL). We performed dose‐exposure simulations targeting steady‐state therapeutic concentrations of 100‐300 ng/mL previously established in adults and children with cardiac dysfunction. We simulated concentrations over 48 hours in typical subjects with decreasing creatinine clearance (CrCl), estimated using the updated bedside Schwartz equation. Seventy‐four patients contributed 111 plasma samples (concentration range, 4‐634 ng/mL). The median (range) postmenstrual age (PMA) was 3.7 years (0‐18), and median weight (WT) was 13.1 kg (2.6‐157.7). The median serum creatinine and CrCl were 0.5 mg/dL (0.1‐3.1) and 117.2 mL/min/1.73 m2 (13.1‐261.3), respectively. A 1‐compartment model characterized the pharmacokinetic data well. The final model parameterization was: Clearance (L/h) = 15.9*(WT [kg] / 70)0.75* (PMA1.12 / (67.71.12+PMA1.12)*(CrCl / 117)0.522; and Volume of Distribution (L) = 32.2*(WT [kg] / 70). A loading dose of 50 µg/kg followed by a continuous infusion of 0.5 µg/kg/min resulted in therapeutic concentrations, except when CrCl was severely impaired at ≤30 mL/min/1.73 m2. In this setting, a 25 µg/kg loading dose and 0.25 µg/kg/min continuous infusion resulted in therapeutic exposures.

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Pharmacology of bipyridine phosphodiesterase III inhibitors

Cited by 68 publications

References 45 publications

Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature

Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature

Effects of Low-dose Milrinone on Weaning from Cardiopulmonary Bypass and after in Patients with Mitral Stenosis and Pulmonary Hypertension

Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents

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