Cardiovascular alterations in rats with Parkinsonism induced by 6-OHDA and treated with Domperidone.

After Alzheimer, Parkinson disease (PD) is the most frequently occurring progressive, degenerative neurological disease. It affects both sympathetic and parasympathetic nervous systems in a variable fashion. Cardiovascular symptoms are present in almost all stages of PD and narrower heart rate variability is the earliest sign. Administration of Levodopa to PD patients has proven to provide some degree of neurological protection. This drug, however, causes side effects including nausea and vomiting, lessened by the administration of domperidone. Autopsies in PD patients led some researchers to suggest the involvement of the ventricular arrhythmia induced by domperidone. The aim of the present study was to determine the impact of the adjusted human maximal dose of domperidone, on cardiological features of Wistar rats. domperidone was administered to both 6-hydroxydopamine Parkinsonism models and regular Wistar rats. Quantitative analysis of ranges of heart beat variation showed significant abnormal distribution in both groups receiving domperidone as compared with respective sham counterparts. However, qualitative analysis of Poincaré plots showed that 6-hydroxydopamine Parkinsonism models receiving domperidone had the narrowest full range of heart beat and the worst distribution heart beat ranges as compared with all study groups corroborating with previous suggestion that domperidone administration to PD patients is likely to play a role in sudden unexpected death in this group of patients.

Repeated Domperidone treatment modulates pulmonary cytokines in LPS-induced acute lung injury in mice.

The dopaminergic antagonist drug Domperidone has immunomodulatory effects. We investigated the effects of repeated Domperidone treatment in a model of Lypopolyssacharide (LPS)-induced acute lung inflammation. Adult C57BL/6J mice were treated with either Vehicle or Domperidone for 5days, and challenged intranasally with LPS in the following day. The behavior of mice was analyzed in the open field and elevated plus-maze test before and 24h after LPS challenge. The bronchoalveolar lavage fluid, blood and lung tissue were collected 24h and 48h after LPS challenge. Domperidone treatment increased LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 production in the bronchoalveolar lavage fluid, without altering tissue damage and the number of immune cells in the lungs and circulation. Locomotor and anxiety-like behavior were unchanged after Domperidone and/or LPS treatment. Cytokine data indicate that Domperidone promotes a change in activity of other cell types, likely alveolar epithelial cells, without affecting immune cell migration in the present model. Due to the role of these cytokines in progression of inflammation, Domperidone treatment may exacerbate a subsequent inflammatory injury.

[Cardiac adverse effects of domperidone in adult patients: a systematic review]. / Efectos adversos cardíacos de la domperidona en pacientes adultos: revisión sistemática.

BACKGROUND: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. AIM: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. MATERIAL AND METHODS: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. RESULTS: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. CONCLUSIONS: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.

Effect of domperidone on QT interval in neonates.

OBJECTIVES: To determine whether oral domperidone is associated with QT interval prolongation and ventricular arrhythmia and to identify factors that can influence these effects. STUDY DESIGN: An electrocardiogram was performed before and after oral administration of domperidone in 31 neonates or infants classified into 3 groups according to gestational age. RESULTS: Oral domperidone is associated with QTc prolongation except in infants with a gestational age less than 32 weeks of amenorrhea (P < .005). Mean QTc prolongation was 14 msec. On univariate analysis, oral domperidone-induced QTc prolongation was correlated with gestational age, birth weight, and elevated serum potassium. On multivariate analysis, after adjustment for gestational age, serum potassium was the only factor independently associated with interval QT prolongation during treatment. No ventricular arrhythmias were observed. CONCLUSIONS: This study shows a significant association between oral domperidone therapy and QTc prolongation. Two risk factors were identified: advanced gestational age and serum potassium at the upper limit of normal. It is recommended that measurement of the QT interval be done before and after oral domperidone therapy.

Domperidone and sudden death.

(1) Domperidone, a "hidden" neuroleptic, is widely used as an oral antiemetic yet its efficacy has not been adequately documented. (2) In a case-control study domperidone was associated with an estimated relative risk of sudden cardiac death of 3.8 (95% confidence interval 1.5-9.7). (3) QT interval prolongation has been reported in an infant on domperidone, with normalisation after domperidone withdrawal. Serious cardiac arrhythmias led to the market withdrawal of the intravenous form of domperidone in the 1980s. (4) In practice, these data represent an additional reason not to use domperidone, or other antiemetics, for mild and transient health problems. Special care is required when other risk factors for QT interval prolongation are present.

QT interval prolongation associated with the oral use of domperidone in an infant.

Gastroesophageal reflux is very common in childhood. If conservative procedures fail to relieve it, the use of a potent antiemetic agent that facilitates gastric motility and emptying, such as domperidone, is justified. We report a 4-month-old child who presented with QT interval prolongation after the oral use of domperidone, which normalized after the drug was discontinued.

Peripheral dopaminergic blockade for the treatment of diabetic orthostatic hypotension.

This study was designed to evaluate the effects of domperidone, a peripheral dopaminergic antagonist, in diabetic patients with symptomatic orthostatic hypotension. Nine patients were admitted to the hospital, placed on a diet containing 150 mEq sodium, and studied for periods of 4 hours, on different days, in the following conditions: (1) supine position, (2) upright posture (UP), (3) UP after 10 mg domperidone, intravenously in bolus, and (4) UP after 3 days of domperidone, 30 mg orally. Before domperidone the mean blood pressure observed in supine position of 132 +/- 37/75 +/- 6 mm Hg fell to 75 +/- 22/57 +/- 13 mm Hg after 2 hours in UP. Acute domperidone did not change the blood pressure response to UP. After 3 days of oral domperidone and in UP for 2 hours, the mean blood pressure value of 89 +/- 21/61 +/- 8 mm Hg was higher than that before domperidone (p less than 0.05), with relief of symptoms in all patients. This blood pressure response to UP has been maintained in six patients who completed 6 months of therapy. No differences were observed in plasma renin activity, aldosterone, sodium, and potassium and in 4-hour urinary excretion of aldosterone, epinephrine, norepinephrine, and dopamine, determined during the UP tests. Administration of domperidone for 3 days reduced the falls in creatinine clearance and the urinary excretion of sodium and potassium induced by UP but did not alter the blood pressure and aldosterone dose-response curves to angiotensin II. Although the mechanism of action is not defined, it is concluded that domperidone is effective for the treatment of orthostatic hypotension in patients with diabetes.

Effects of domperidone therapy on symptoms and upper gastrointestinal motility in infants with gastroesophageal reflux.

We evaluated the effect of domperidone, a novel prokinetic agent, on symptoms and esophageal and gastric motility in 15 infants (six boys), mean age 7.9 months, with moderate to severe gastroesophageal reflux (GER) and upper gastrointestinal motility disturbances. Patients received domperidone orally for 6 weeks and underwent weekly assessment of five GER-associated symptoms, weight change, and side effects. Mean total symptom scores significantly improved after treatment (P less than 0.01). Vomiting, "spitting," and coughing each improved significantly. Postprandial reflux time (defined as esophageal pH less than 4.0) and percent peristaltic esophageal contractions improved significantly (p less than 0.05). Gastric fundic contractions, present in only four infants before treatment, occurred in nine after domperidone administration. Although mean gastric emptying of isotope-labeled formula was not improved, it improved greater than or equal to 10% over baseline in nine patients. Peristaltic amplitude, lower esophageal sphincter pressure, and esophageal acid clearance time were unchanged. Side effects were minimal. We conclude that domperidone is a useful and safe agent for treatment of gastroesophageal reflex in infants because it addresses the motility abnormalities inherent in the pathophysiology of the disorder.