Mg Of Bromocriptine Research Articles

The effects of bromocriptine in patients with congestive heart failure

The sympathetic nervous system and the renin-angiotensin system are activated in patients with congestive heart fallure (CHF) and could be contributing to excessive peripheral vasoconstriction and impaired myocardial performance. Bromocriptine, an orally active ergot alkaloid with dopaminergic receptor agonist actions, is known to lower plasma norepinephrine in humans. It could also possess direct vasodilator activity through vascular dopaminergic receptors. To assess the effects of bromocriptine on hemodynamic measurements, sympathetic nervous system activity, and the renin-angiotensin system in patients with heart failure, we measured standard hemodynamic parameters and plasma norepinephrine and plasma renin activity before and following a single oral dose of 2.5 mg of bromocriptine in 10 patients with chronic stable heart failure. The following statistically significant ( p < 0.01) peak responses were noted: plasma norepinephrine decreased from a mean ± 1 SD of 581 ± 194 to 366 ± 181 pg/ml; mean heart rate declined from 87 ± 16 to 78 ± 17 bpm; mean blood pressure was reduced from 87 ± 9 to 73 ± 9 mm Hg; systemic vascular resistance decreased from 1494 ± 361 to 1249 ± 289 dynes · sec · cm −5; stroke volume index increased from 27 ± 7 to 33 ± 10 ml/beat/M 2; left ventricular filling pressure decreased from 28 ± 8 to 21 ± 8 mm Hg; and mean right atrial pressure fell from 10 ± 4 to 7 ± 4 mm Hg. Plasma renin activity did not change significantly. All patients tolerated the drug well. Although the effects of bromocriptine on plasma norepinephrine may contribute to an improved hemodynamic state, other mechanisms of action are likely. A direct vasodilator effect via vascular dopaminergic receptor stimulation is possible. We conclude that bromocriptine improves the hemodynamic profile in heart failure acutely and that long-term studies are appropriate to better characterize the role of this agent.

Pituitary responsiveness to LHRH and TRH in men: effect of bromocriptine and clomiphene treatment.

The effect of the concomitant use of bromocriptine and clomiphene on pituitary function was tested in 8 healthy men, who ingested either 100 mg of clomiphene, 5 mg of bromocriptine or 100 mg of clomiphene +5 mg of bromocriptine daily for 7 days. Plasma concentrations of FSH and LH increased similarly during clomiphene and clomiphene + bromocriptine intake. Bromocriptine decreased the plasma levels of prolactin (Prl) and this decrease was unaffected by clomiphene. The latter blunted the plasma LH response to LHRH whilst bromocriptine blunted the Prl response to TRH, but Clomiphene and bromocriptine together had no additive effects on gonadotrophin and Prl secretion. It thus seems likely that this combination offers no advantage over clomiphene alone in the treatment of normoprolactinaemic infertile men.

Cavernous sinus syndrome due to prolactinoma: Resolution with bromocriptine

Cavernous sinus syndrome due to a pituitary tumor is quite rare. Our patient had a large prolacinoma that extended superiorly, causing bitemporal visual field defects, and laterally into the right cavernous sinus, causing tearing, dysesthesia in the distribution of the fifth cranial nerve, a loss of the corneal reflex, and a sixth cranial nerve palsy. Prolactin levels ranged between 800 and 1000 ng/mL. Treatment with 7.5 mg of bromocriptine daily caused a marked reduction in the size of the tumor and resolution of her visual field defects and cranial nerve dysfunction over 6 months. We feel that bromocriptine should be considered as initial therapy for patients with prolactinomas extending into the middle or posterior cranial fossae.

Restoration of ovarian function by low nocturnal single daily doses of bromocriptine in patients with the galactorrhea-amenorrhea syndrome

Eighteen hyperprolactinemic patients with either amenorrhea or both galactorrhea and amenorrhea were treated with 2.5 mg of bromocriptine per day supplied at night. Ovulation occurred in 16 patients, and 8 wishing to conceive became pregnant. One of these patients became pregnant for a second time at a bromocriptine dose as low as 1.25 mg/day. Normal ovulatory cycles in four women receiving 2.5 mg of bromocriptine per day could also be maintained at 1.25 mg, despite the differences in the degree of prolactin (PRL) inhibition. Progesterone and luteinizing hormone levels measured for both bromocriptine levels were consistent with ovulatory cycles. The low, single dose of bromocriptine per day supplied at night decreased PRL levels, but normalization of blood levels did not always occur. Eighty percent of the patients ovulated with prolactin values over 25 ng/ml (normal value = less than 20 ng/ml).

15 EFFECT OF BROMOCRIPTINE ON THE SECRETION ON PITUITARY HORMONES IN CHILDREN

Top of pageAbstract We have previously demonstrated that in normal children Bromocriptine(BRE) at a dose of 1.25mg per os induced HGH secretion without modifying FSH and LH levels. A marked decrease in sistolic(S) and diastolic(D) blood pressure was also found (X Δ/B S-22; D-12mm Hg). The present work has a dual purpose a) to find out a proper dosage of BRE devoid of side effects on the cardiovascular system and b) to study its effect on prolactin secretion. 17 children ranging in age from 6-17 years old, without any endocrine pathology were studied. 8 patients received 1.25mg of BRE per os; (Group I);5 patients received 0.62mg per os (Group II);and 4 were given BRE after insulin stimulation (2:1.25mg and 2:0.62mg)(Group III). Plasma levels of HGH and PRL were measured by RIA. An increase in HGH levels was observed in group I, basal X= 5.71 ± 1.8(S.E.)ng/ml, maximun increment (MI) X 16.Ong/ml. In group II HGH levels were also raised with basal X=5.4ng/ml and M.I. X= 15ng/ml. A minor effect on blood pressure was found with this dose (XΔ/B S-9; D-4mm Hg). Basal levels of PRL in group II were 29 ± 9,8ng/ml and they decreased to 4.3 ± 0.52ng/ml at 180′. We conclude that BRE 0.62mg per os is enough to produce endocrine changes without cardiovascular side effects in children.

Follow-up study on treatment in 27 patients with Cushing's disease: adrenalectomy, transsphenoidal adenomectomy and medical treatment.

27 patients with Cushing's disease were treated over a period of 18 years at the Departments of Medicine and Surgery, Nagoya University School of Medicine and the following results were obtained. 1) Adrenalectomy. 21 of 27 patients with Cushing's disease underwent adrenalectomy. 19 patients had total bilateral adrenalectomy and 2 patients unilateral adrenalectomy. 4 patients died, the cause of death not being related directly to adrenalectomy. 9 of 15 bilaterally adrenalectomized patients had hyperpigmentation even though they had been given substitution therapy with cortisol 20-30 mg daily. They had elevated plasma ACTH levels, which were not completely suppressed by 2 mg of dexamethasone or 2.5 mg of bromocriptine per day. 2) Adenomectomy, 5 patients had adenomectomy via the transsphenoidal approach. 3 patients were cured but one of them has required postoperative substitution therapy with cortisol for hypopituitarism for one year until today. 2 of 5 adenomectomized patients had a recurrence of Cushing's syndrome after remission for 6-8 months. One of these recurrent cases has been subsequently treated successfully with bromocriptine, a dopaminergic drug. 3) Medical treatment. 2.5 mg per day of bromocriptine has been effective in 2 patients without a pituitary adenoma and ineffective in the other 4 patients with a pituitary adenoma. 24 mg per day of cyproheptadine, an antiserotoninergic drug was not effective in any of the 4 patients with a pituitary adenoma.

Gastrointestinal side-effects of bromocriptine.

Basal plasma levels of insulin, gastrin, secretin, vasoactive intestinal polypeptide and N-terminal and C-terminal glucagon immunoreactivity were measured in 6 fasting hyperprolactinaemic patients following the ingestion of 2.5 mg bromocriptine. No significant changes occurred in the basal plasma levels of these hormones up to 3 hours after bromocriptine ingestion. In a further 10 similar patients studies were carried out on the effect of bromocriptine on the release of these hormones following a standard mixed meal containing 50g carbohydrate, 18g protein and 20g fat with a total energy value of 1.9 megajoules. Plasma hormone levels were measured at 15 minute intervals for 2 hours after ingestion of the meal on 2 occasions—first without bromocriptine and second one hour after 2.5 mg of bromocriptine orally. Following the meal mean plasma glucose levels rose from 5.1±0.2 to 7.6±0.4 mmol/l and from 4.9±0.2 to 7.1±0.4 mmol/l before and after bromocriptine respectively. Mean plasma insulin levels rose from 7.5±0.5 to 84±12 mU/l before bromocriptine but only from 7.0±0.5 to 52.5±12.5 mU/l after bromocriptine. The responses of plasma gastrin, secretin, vasoactive intestinal polypeptide, N-terminal and C-terminal glucagon-like immunoreactivity were not significantly altered by bromocriptine. Seven of the 10 patients were extremely nauseated and 3 vomited just after the study was completed on the day bromocriptine was given.

Stimulatory Effect of Clebopride on Human Prolactin Secretion

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Bromocriptine treatment during early human pregnancy: effect on the levels of prolactin, sex steroids and placental lactogen

To elucidate the role of prolactin (Prl) in the endocrinology of early human pregnancy, 28 healthy women were given 5.0-7.5 mg of bromocriptine daily for two weeks between weeks 6-9 of normal gestation. Plasma Prl, oestradiol-17 beta (Oe2), progesterone (P), testosterone (T) and human placental lactogen (hPL) were measured before, and one and two weeks after the start of bromocriptine, and they were compared with those in 22 control women who were followed similarly but without bromocriptine treatment. Bromocriptine treatment induced a significant Prl depression at one week (7.3 +/- 4.3 ng/ml vs 23.7 +/- 11.4 ng/ml) and two weeks (5.3 +/- 2.5 ng/ml vs 31.9 +/- 16.4 ng/ml). Oe2, P, T and hPL levels, however, showed no significant differences between the groups. Two women undergoing bromocriptine treatment (7.1%) and one control women (4.5%) experienced spontaneous incomplete abortion during the study period, but these three already had a low Oe2 level and a low/or undetectable hPL level at the beginning of the study. It is obvious that neither maternal 'hypoprolactinaemia' nor bromocriptine during early human pregnancy interfere with the normal progress of pregnancy or with the normal synthesis of sex steroids and hPL at this time.

Prolactin modulation of dehydroepiandrosterone sulfate secretion

To clarify the controversy about the effect of prolactin (PRL) on dehydroepiandrosterone sulfate (DHEA-S), this study was undertaken to investigate the effects of alterations in plasma PRL on plasma DHEA-S concentrations in hyperprolactinemic women, as well as in normal male subjects. DHEA-S was measured in a group of 21 women with hyperprolactinemia, galactorrhea, and amenorrhea (PRL: 257 ± 89 ng/ml; mean ± SEM). In these women, mean plasma concentrations of DHEA-S (2.54 ± 0.2 μg/ml) were significantly higher (p < 0.005) than those in 41 normal control women (1.78 ± 0.1 μg/ml) and those in a group of 11 amenorrheic patients (1.77 ± 0.2 μg/ml). Eight women with hyperprolactinemia were given 5 mg of bromocriptine each day for 4 consecutive weeks. Within 1 week of medication, PRL levels fell by 60% (p < 0.05). To test whether lowering normal plasma levels of PRL would affect plasma concentrations of DHEA-S, five normal male subjects received a 48-hour infusion of dopamine at an average rate of 6 μg/kg/min. Plasma levels of PRL fell by 60% (p < 0.01) after 8 hours of infusion, and DHEA-S decreased by 27% by 16 hours (p < 0.05). These data suggest that PRL modulates the secretion of DHEA-S: an increase in plasma levels of PRL is correlated with elevated concentrations of DHEA-S, whereas a decrease in PRL is followed by a fall in DHEA-S.

The use of bromocriptine for testing central dopaminergic reactivity.

A single oral intake of 10 mg of Bromocriptine can modify both plasma renin activity (PRA) and arterial blood pressure (BP). The changes in both variables depend on the integrity of the central dopaminergic systems. The parkinsonians whose extrapyramidal symptoms are markedly improved by L-Dopa in association with a decarboxylase inhibitor (IDC) and the untreated parkinsonians are the only patients whose PRA and BP are lowered 1 h after Bromocriptine ingestion. The results obtained in the L-dopa-induced dyskinetic parkinsonians are similar to those obtained in the group of L-Dopa-resistant patients. This points to the paradoxical hypothesis of dopaminergic hyposensitivity in the dyskinetic patients. In spite of the absence of correlation between PRA and BP, it is possible that lowering of BP by Bromocriptine is linked to the parallel decrease of PRA. An increase of the BP may be obtained in the dyskinetic and L-Dopa-resistant groups. These data point to a possible involvement of central dopaminergic systems in some aspects of hypertension.

Dopaminergic control of aldosterone secretion in man (author's transl)

To evaluate the dopaminergic control of aldosterone secretion, the following experiments were performed on 10 normal subjects (3 men and 7 women, aged 21 approximately 69 yrs.), 16 diabetics (8 men and 8 women, aged 20 approximately 74 yrs.) and 7 patients with untreated hyperthyroidism (2 men and 5 women aged 16 approximately 58 yrs.). Blood samples were withdrawn from an intravenous cannula indwelled in an antecubital vein at 0, 15, 30, 45, 60, 90 and 120 min after intravenous injection of 10mg metoclopramide with a volus. Plasma aldosterone levels and plasma renin activities (PRA) were measured by radioimmunoassay. In normal subjects, plasma aldosterone levels were significantly increased from basal levels of 111.8 +/- 1.3 Opg/ml (Mean +/- S.E.) to 183.4 +/- 23.3pg/ml 15 min after an intravenous injection of metoclopramide and were sustained for about 90 min. This increase induced by metoclopramide was, however, abolished by pretreatment with 2.5mg of bromocriptine. It is suggested that metoclopramide and bromocriptine are in a competitive relationship at the level of dopaminergic receptor. In diabetics, the mean plasma level of aldosterone was as low as 66.3 +/- 8.7pg/ml, which was significantly lower than that in normal subjects (p less than 0.01), and aldosterone response to metoclopramide was significantly diminished. Although this tendency was more apparent in diabetics with such complications as neuropathy or retinopathy, aldosterone response to metoclopramide implied that aldosterone secretion was under dopaminergic inhibition in this hypoaldosteronemic state. While aldosterone responded well to metoclopramide, PRA was not significantly altered in this treatment in normal subjects and diabetics. In patients with untreated hyperthyroidism, aldosterone response was similar to that in normal subjects.

Abnormal prolactin levels in serum and seminal plasma in infertile men.

The role of prolactin in male infertility was studied in 33 patients in whom serum and seminal plasma prolactin levels were determined. With the exception of those patients with Klinefelter's syndrome, infertile males presented moderate hyperprolactinemia as compared with a control group of 34 men. Prolactin levels in seminal plasma were greater than in serum in all patients studied; however, prolactin levels in infertile patients were significantly less than in normal males. Therefore, this situation is the reverse of what happens in serum. Seven patients with idiopathic oligospermia were treated with 5 mg of bromocriptine daily during 6 months, resulting in no measurable effect on the sperm count. Infertility in men may be associated with moderate hyperprolactinemia but bromocriptine is of no therapeutic use. Interpretation of the abnormal levels of prolactin in seminal plasma in oligo- and azoospermic men requires further investigation.

Effects of bromocriptine on pituitary tumour size.

In a prospective study designed to assess the influence of bromocriptine on pituitary tumour size 12 patients with pituitary tumours, eight of whom had suprasellar extensions, were treated for three months with 20 mg of bromocriptine daily after a gradual increase to this dose. The group comprised eight women and four men, five with prolactin-secreting adenomas, four with acromegaly, two with functionless adenomas, and one with Nelson's syndrome. All five patients with prolactin-secreting adenomas showed a reduction in pituitary tumour size as assessed by computerised tomography and metrizamide cisternography accompanied by a fall in prolactin concentrations and clinical and biochemical improvement in their hypopituitarism. One patient in this group had a visual-field defect before treatment, and this resolved. There was no radiological evidence of reduction in tumour size in the remaining seven patients, though this might refect the fairly short duration of treatment, particularly in view of the ancillary evidence of clinical, biochemical, and visual-field improvement in some of the patients. These results emphasise the potential value of bromocriptine in treating patients with large prolactinomas or recurrences of such tumours after previous chiasmal decompression and conventional external megavoltage irradiation on the pituitary.

RESTORATION OF OESTROGEN POSITIVE FEEDBACK EFFECT ON LH RELEASE BY BROMOCRIPTINE IN HYPERPROLACTINAEMIC PATIENTS WITH GALACTORRHOEA-AMENORRHOEA

Five mg of bromocriptine was administered for 3 weeks to 8 hyperprolactinaemic women with galactorrhoea-amernorrhoea, in whom the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to 100 micrograms of iv LH-releasing hormone (LH-RH) had been evaluated. Twenty mg of conjugated oestrogen (Premarin) was injected iv any day between the 10th and 12th day from the initiation of the treatment, and serum LH levels were serially determined for 120 h. Hyperresponse of LH with normal FSH response to LH-RH was observed in most patients. Bromocriptine treatment for 10 to 12 days significantly suppressed mean (+/- SE) serum prolactin (PRL) levels from 65.1 +/- 23.0 to 10.4 +/- 2.0 ng/ml, while LH (12.6 +/- 2.1 to 24.8 +/- 5.9 mIU/ml) and oestradiol (40.1 +/- 7.6 to 111.4 +/- 20.8 pg/ml) levels increased significantly. Patients on bromocriptine treatment showed LH release with a peak at 48 h after injection of Premarin. The mean per cent increases in LH were significantly higher than those in untreated patients with galactorrhoea-amenorrhoea between 32 and 96 h after the injection. The present results seem to suggest that the restoration of LH-releasing response to oestrogen following suppression of PRL by bromocriptine may play an important role in induction of ovulation in hyperprolactinaemic patients with galactorrhoea-amenorrhoea.

Bromocriptine and dopaminergic function in Huntington disease

The cerebrospinal fluid (CSF) content of homovanillic acid (HVA) was assayed in 10 patients with Huntington disease. On doses of less than 40 mg of bromocriptine daily, there was clinical improvement and the CSF HVA concentration increased. On higher doses of bromocriptine, chorea worsened and the CSF HVA concentration decreased. Bromocriptine at low dosage seems to act as a partial dopamine antagonist, with phenothiazine-like effects, and at higher doses it acts as a direct dopamine-receptor stimulating agent.

BROMOCRIPTINE ASSOCIATED WITH A PERIPHERAL DOPAMINE BLOCKING AGENT IN TREATMENT OF PARKINSON'S DISEASE

A peripheral dopaminergic blocking agent, domperidone (60 mg daily), or placebo was given, double-blind, to 17 parkinsonian patients who also received increasing doses of bromocriptine. Combined treatment with domperidone reduced total disability by 76% in 8 patients receiving a mean dose of 148 mg of bromocriptine daily. There was no vomiting and involuntary movements and psychic disturbances were similar to those in patients on levodopa and a peripheral decarboxylase inhibitor. In 9 patients taking placebo instead of domperidone, the average daily dose of bromocriptine could not be raised beyond 92 mg. The mean total disability score in this group was reduced by only 48%. Thus, peripheral blockade of dopamine receptors is a promising means of limiting the adverse side-effects of the treatment of parkinsonism with central dopaminergic receptor stimulating agents such as bromocriptine.

Treatment of hyperprolactinemic luteal insufficiency with bromocriptine.

Twelve patients with infertility and insufficent luteal function were studied during a control cycle, and during a cycle when 2.5 mg of bromocriptine was given twice daily. Serum levels of prolactin, progesterone, estradiol-17-beta, FSH and LH were determined during both cycles. Endometrial biopsies were taken from most patients during the late luteal phase. Two patients had persistent hyperprolactinemia, approximately 35-45 ng/ml, and both had repeated insufficient luteal function, which completely reverted to normal during treatment. Five of the 10 normoprolactinemic patients achieved a normal luteal function during bromocriptine therapy. No pregnancies were achieved during the study but one patient later conceived during bromocriptine therapy.

Ergot derivatives for Parkinsonism.

The response of Parkinsonism to three ergot derivatives which modify dopaminergic transmission was studied. CF 25-397 behaved more as an antagonist than an agonist. Lergotrile was an agonist with therapeutic properties marred by prominent hepatotoxicity. Bromocriptine is an effective anti-Parkinsonian agent, particularly useful in patients with prominent dyskinesia or "on-off" reactions to levodopa; in most patients optimal results have been obtained by combining from 40 to 90 mg of bromocriptine daily with approximately 60% of the previous maximal dose of levodopa. Unfortunately, only some 50% of patients tolerate long-term bromocriptine therapy, but all adverse reactions have been dose dependent and reversible.

Lack of effect of bromocriptine on ACTH levels in patients with bilateral adrenalectomy for pituitary-dependent Cushing’s syndrome

Bromocriptine lowers plasma ACTH levels in patients with pituitary-dependent Cushing's syndrome. It seemed possible that the drug would also be effective in patients who had been adrenalectomised for the disease. The effect of 5.0 mg of bromocriptine on plasma ACTH and prolactin levels in 13 patients, bilaterally adrenalectomised for pituitary-dependent Cushing's syndrome, was therefore studied. In only one patient was a fall in plasma ACTH observed. This may be of doubtful significance since marked spontaneous fluctuation in plasma ACTH levels were found in the five patients tested. Bromocriptine lowered the plasma prolactin in all of the patients, including two with hyperprolactinaemia.