Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bromocriptine, a lysergic acid derivative with a bromine atom at position 2, has been found to have unique effects on the dopamine receptors in the pituitary and central nervous system and peripherally. It is rapidly and completely absorbed from the gut and is mainly excreted in the bile and faeces. It seems to have a particular specificity for the pituitary prolactinotrophe although it does have other effects in different diseases states. In spite of the fact that it is an ergot derivative, it is remarkably free of ergot vascular side effects in the doses needed for therapeutic benefit. The most common adverse effect are nausea, vomiting and postural symptoms. These can be overcome by starting at low doses and increasing the therapeutic levels. Its major use is in the suppression of prolactin in states where this hormone is elevated irrespective of cause. It has also been used in the treatment of acromegaly and is under investigation for use in other disease states probably linked with prolactin system or dopaminergic receptors.
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PMID:Pharmacology of bromocriptine in health and disease. 22 67

Thirty-one patients with Parkinson's disease were treated with the ergot alkaloid bromocriptine, a drug which stimulates dopamine receptors. Bromocriptine had a slight therapeutic effect in patients on no other treatment and an additional effect in patients on levodopa. The mean optimum dosage of bromocriptine, established over a 12 week period, was 26 mg daily. In 20 patients bromocriptine was compared with placebo in a double-blind controlled trial. Active treatment caused a significant (P less than 0.02) reduction in total disability and akinesia scores. The least disabled patients showed the greatest response. Side-effects of bromocriptine--nausea, vomiting, hallucinations, and abnormal involuntary movements--were similar to nature to those of levodopa. In most normal subjects, bromocriptine causes an increase in plasma growth hormone concentration. This was determined in 20 patients with Parkinson's disease after 1-15 mg bromocriptine. Only a single patient showed an obvious increase up to 120 minutes after dosage. Bromocriptine was not effective treatment in two patients who had not previously responded to levodopa and replacement of this drug by bromocriptine in patients with end-of-dose akinesia after chronic levodopa treatment did not totally abolish response swings.
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PMID:Bromocriptine treatment in Parkinson's disease. 77 75

Thirty-seven patients with Parkinsonism were treated with bromocriptine 2.5-300 mg daily. Bromocriptine, alone or combined with levodopa, caused a 20-30% reduction in disability scores in 11 patients treated for one year. Tolerance did not develop during this period. Bromocriptine treatment was not of value in six patients who had previously not responded or who had lost their response to levodopa. However, in four of five patients with response swings on levodopa due to rapid changes in plasma dopa levels, the addition of bromocriptine caused a more stable response. Dose response curves to bromocriptine 12.5, 25, 50, and 100 mg and to levodopa 250, 500, 1000, and 2000 mg were studied in seven patients. Levodopa 2 g had a greater therapeutic effect and caused a greater rise in plasma growth hormone concentration than bromocriptine 100 mg. Levodopa caused emesis more commonly and hallucinations less commonly than bromocriptine. Bromocriptine appears to be a less potent stimulant than dopamine, and has both pre- and post-synaptic effects. Metoclopramide 60 mg oral was given 30 minutes before bromocriptine or levodopa to establish whether this caused dopamine-receptor blockade. Metoclopramide acted as a competitive antagonist to the anti-Parkinsonism and growth hormone effect of both drugs and in individual cases prevented emesis and hallucinations. The fall in blood pressure due to bromocriptine or levodopa was not antagonised by metoclopramide. Central and peripheral vascular dopamine receptors may be different in nature.
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PMID:Bromocriptine in Parkinsonism: long-term treatment, dose response, and comparison with levodopa. 103 99

Bromocriptine (CB-154) and the 8-alpha-ergoline CU 32-085, two dopamine receptor agonists, were administered at different times to two series of 22 patients with Parkinson's disease, most of whom took levodopa (plus benserazide) at optimum dosage. The addition of bromocriptine (mean daily dose 32 mg; after 6 months 40 mg) led to a 38.5% reduction of levodopa, while CU 32-085 (mean daily dose 15.2 mg; after 6 months 17.5 mg) permitted a 33.7% reduction in levodopa. The mean dose in two patients on CU 32-085 monotherapy was 55 mg/day. A total of 15 patients tolerated adequate doses of bromocriptine (5-75 mg/day, mean duration of treatment 7.5 months) and 15 patients long-term treatment up to 14 months with CU 32-085 (dose range 1-60 mg/day; mean duration 8.8 months). Both groups showed a significant improvement of "total disability score' at 6 months by 56% and 67%, respectively, and after 6 months by 69% and 69.4%, respectively, with a significant decrease of all types of disability. All patients with fluctuations and "on-off' effects rapidly improved on both compounds. Bromocriptine and CU 32-085 were discontinued in seven patients each (32%) because of adverse effect including mental changes (for with bromocriptine, two with CU 32-085), nausea and vomiting (one and two, respectively), hypotension (one each) and increased tremor plus vomiting (one with CU 32-085). Although adverse effects were similar to those observed with levodopa, CU 32-085 in general showed less severe dyskinesia and mental changes but more frequent nausea than bromocriptine and levodopa. While the results of treatment with bromocriptine and CU 32-085 were comparable, the antitremor effect of the latter drug developed more rapidly, even at low dosage. Both compounds were useful in the management of patients with advanced Parkinson's disease, CU 32-085 having a stronger effect on tremor, bradykinesia, fluctuations and "on-off' effects than bromocriptine.
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PMID:Adjuvant treatment of Parkinson's disease with dopamine agonists: open trial with bromocriptine and CU 32-085. 618 Jan 42

Cabergoline is a synthetic ergoline which shows high specificity and affinity for the dopamine D2 receptor. It is a potent and very long-acting inhibitor of prolactin secretion. Prolactin-lowering effects occur rapidly and, after a single dose, were evident at the end of follow up (21 days) in puerperal women, and up to 14 days in patients with hyperprolactinaemia. In the only comparative study to date, cabergoline 0.5 to 1.0 mg twice weekly was more effective than bromocriptine 2.5 to 5.0 mg twice daily in the treatment of hyperprolactinaemic amenorrhoea, restoring ovulatory cycles in 72% of women and normalising plasma prolactin levels in 83%, compared with 52 and 58%, respectively, for bromocriptine. In the prevention of puerperal lactation, a single dose of cabergoline 1.0mg was as effective as bromocriptine 2.5mg twice daily for 14 days. A significantly lower incidence of rebound lactation in the third postpartum week was seen with cabergoline. Unpublished data suggest cabergoline 0.25mg twice daily for 2 days is effective in suppressing established puerperal lactation in about 85% of women. Nausea, vomiting, headache and dizziness are characteristic adverse events of the dopaminergic ergot derivatives. Cabergoline appears to be better tolerated than bromocriptine in both patients with hyperprolactinaemia and postpartum women. Most patients intolerant of other ergot derivatives can tolerate cabergoline. Bromocriptine use in the puerperium has been associated with an increased risk of serious thromboembolic events. However, there are no such reports with cabergoline and whether these events will become associated with other dopaminergic agents is unknown. The teratogenic potential of cabergoline has not been extensively investigated in humans. Ten congenital abnormalities have been reported in 199 cabergoline-associated pregnancies. Although there is no pattern to these abnormalities, the limited experience with cabergoline in pregnancy means the drug cannot be considered as a first-line therapy for the treatment of infertility associated with hyperprolactinaemia. At this stage of its development, cabergoline will prove useful in patients with hyperprolactinaemia who have failed treatment with, or are intolerant of, other dopamine agonists such as bromocriptine. If drug treatment is required for the prevention or suppression of puerperal lactation, cabergoline offers significant advantages over bromocriptine and should become the drug treatment of first choice for this indication.
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PMID:Cabergoline. A review of its pharmacological properties and therapeutic potential in the treatment of hyperprolactinaemia and inhibition of lactation. 772 32

A prolactin-secreting pituitary tumour is the most frequent cause of hyperprolactinaemia that commonly occurs in clinical practice. Prolactinomas occur more frequently in women than in men and may differ in size, invasive growth and secretory activity. At presentation, macroadenomas are more frequently diagnosed in men. Specific immunohistochemical stains are necessary to prove the presence of prolactin in the tumour cells. The main investigations in the diagnosis of a prolactin-secreting adenoma are hormonal and radiological. As prolactin is a pulsatile hormone, it is a general rule to obtain several blood samples by taking a single sample on 3 separate days or 3 sequential samples (every 30 minutes) in restful conditions. Prolactin levels of 100 to 200 micrograms/L are commonly considered diagnostic for the presence of a prolactinoma; however, prolactinoma cannot be excluded in the presence of lower levels, and prolactin levels > 100 micrograms/L are present in some patients with idiopathic hyperprolactinaemia. Several dynamic function tests have been proposed to differentiate idiopathic from tumorous hyperprolactinaemia. Although they could be used for group discrimination, these tests cannot be used for individual patients. To differentiate between a prolactinoma and a pseudoprolactinoma, thyrotrophin response to a dopamine receptor antagonist may be used, as only prolactinomas may have an increased response. A short course of dopaminergic drugs may also be of some help, as in macroprolactinomas only a shrinkage may be observed. After hyperprolactinaemia is confirmed, imaging with computerised tomography (CT) and magnetic resonance imaging (MRI) are necessary to define the presence of a lesion compatible with a pituitary tumour. There is now a general agreement that medical therapy is of first choice in patients with prolactinomas. Bromocriptine, the most common drug used in this condition, is a semisynthetic ergot alkaloid that directly stimulates specific pituitary cell membrane dopamine D2 receptors and inhibits prolactin synthesis and secretion. In most patients, a reduction or normalisation of prolactin levels is usually observed, together with the disappearance or improvement of clinical symptoms. The sensitivity to bromocriptine is variable and patients may need different dose of the drug. Bromocriptine is also able to shrink the tumour in most patients; however, a few reports of disease progression during therapy have been described. The need for close follow-up, including prolactin levels and CT or MRI studies, is therefore emphasised. Bromocriptine is conventionally given in 2 or 3 daily doses; however, a single evening dose has been shown to be equally effective. Bromocriptine is usually well tolerated by the majority of patients; some adverse effects (nausea, vomiting, postural hypotension) may be initially present, but they usually wear off in time. To prevent such adverse effects it is advisable to start treatment with a low dose during the evening meal and gradually increase the dose over days or weeks. A few patients are unable to tolerate oral bromocriptine, so different formulations of bromocriptine or alternative dopamine agonist drugs (lisuride, terguride, metergoline, dihydroergocryptine, quinagolide, cabergoline, pergolide) have been proposed. Of particular clinical relevance because of their good tolerability and sustained activity are cabergoline and quinagolide. Particular attention should be paid to pregnancy in prolactinoma patients, as tumour enlargement has been reported. As the risk for this occurrence is low in patients with microprolactinoma, there is a general agreement that the drug can be stopped once pregnancy is diagnosed. In patients with macroprolactinoma the risk of tumour enlargement is higher. Therefore, primary therapy with bromocriptine until the tumour has shrank is suggested before pregnancy is attempted. Bromocriptine should be stopped as soon as pregnancy is confirmed, but re
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PMID:Diagnosis and drug therapy of prolactinoma. 873 17

Clinical evidence and recent genetic findings seem to indicate an involvement of dopamine in the pathophysiology of the migraine attack. Prodromal symptomatology (mood changes, yawning, drowsiness, food craving), accompanying symptoms (nausea, vomiting, hypotension) and postdromal symptoms (mood changes, drowsiness, tiredness) may be related to dopaminergic activation. The dopaminergic system could also play a role in the headache phase, either by taking part in nociception mechanisms, or by regulating cerebral blood flow. A body of pharmacological findings seems to support this involvement. Migraine patients, between attacks, show a higher responsiveness to acute administration of dopaminergic agents. Apomorphine administration induces in migraineurs more yawns as well other dopaminergic symptoms e.g. nausea, vomiting, dizziness. Migraine has been associated with hypotension and, occasionally, with syncope. Bromocriptine causes severe orthostatic syndrome in migraine patients. Both piribedil and apomorphine markedly increase cerebral blood flow of migraine patients, thus indicating enhanced responsiveness of dopamine receptors which are involved in cerebral blood flow regulation. Interictal dopaminergic hypersensitivity has also been demonstrated by means of neuroendocrine tests. Altered dopaminergic control of prolactin secretion exists in migrainous women. L-deprenyl, a MAO-B inhibitor, is significantly more effective in reducing prolactin levels in migraineurs than in controls. Taken together, these findings support the view that hypersensitivity of peripheral and central dopaminergic receptors is a specific migraine trait. Finally, a high density of lymphocytic D5 receptors has been found in migraine sufferers, thus suggesting their upregulation. Therefore, the hypothesis that dopaminergic activation is a primary pathophysiological component in certain subtypes of migraine, namely those characterised by marked dopaminergic symptomatology, has been advanced. From this perspective, a blockade of dopaminergic hyperresponsive receptors can be considered as a rationale for the therapy of migraine.
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PMID:Dopamine involvement in the migraine attack. 1120 Jul 88

We report a pregnant woman with a large macroprolactinoma successfully treated with cabergoline after a suboptimal response to bromocriptine. A 7 week pregnant woman with a history of a prolactinoma presented to the endocrine clinic with the complaints of headaches and nausea. She had a prolactin level of 65 microg/L 1 1/2 weeks following her last menstrual period. Bromocriptine was discontinued at 6 weeks gestation when pregnancy was confirmed. A PRL concentration was 1899 microg/L (non-pregnant normal range 1.39-24.20 microg/L, the mean peak levels during pregnancy reported from the literature are 200-210 microg/L) at 7 weeks gestation, and a repeat was 2197 microg/L. An MRI showed a 3 x 2.2 x 2.5 cm seller mass abutting the optic chiasm and displacing the optic nerves superiorly; the visual field testing was normal. Bromocriptine was reinitiated and the patient responded initially with decreasing headaches and declining PRL concentrations to 1488 microg/L at 15 weeks gestation. However, PRL increased to 1836 microg/L at 16 weeks and remained elevated despite bromocriptine 2.5 mg three times a day; in addition, she complained of severe nausea, vomiting, and persistent headaches. Cabergoline was added at 18 weeks gestation. PRL decreased dramatically from 1710 to 859 microg/L in 1 week, and to 488 microg/L within 4 weeks. A repeat MRI showed more than 30% reduction in tumor size. Bromocriptine was discontinued at 24 weeks gestation; she was maintained on cabergoline 0.5 mg twice a week without complaints. PRL levels ranged from 190 to 278 microg/L during the last 10 weeks of pregnancy. She had a C-section electively at 37 weeks gestation and delivered a healthy baby. Management options in this patient and during pregnancy are discussed.
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PMID:Successful treatment of a large macroprolactinoma with cabergoline during pregnancy. 1213 91

During pregnancy, the maternal, placental and fetal physiological characteristics constantly evolve and thereby constantly alter drug bioavailability in the mother and feto-placental unit. Gastric emptying time is increased and bowel movements are reduced. Distribution in the maternal body is mainly influenced by body mass variations, water content and fat stores. Metabolic capacity of the liver appears unchanged but renal clearance of drugs is gradually increased. The placental transfer of most drugs mainly consists of passive diffusion between the maternal and fetal circulations, along their respective concentration gradients. Only the free, unbound and non-ionized fraction of the drug readily crosses the membranes. Four anti-hypertensive drugs have been granted a license for the treatment of PE since the year 2000: these are Clonidine (Catapressan), Nicardipine (Loxen+), Labetalol (Trandate), Dihydralazine (Nepressol). Dihydralazine, Labetalol and Nicardipine are not contraindicated in the breast feeding mother. The administration of a long acting Benzodiazepine during pregnancy can lead to new born intoxication of variable severity and duration. These symptoms may precede a withdrawal syndrome (hyper-excitability, tremor, gastro-intestinal upset, such as diarrhea or vomiting). Breast feeding by mothers using benzodiazepines (Nitrazepam and Midazolam) is not recommended. In France, the use of low molecular weight heparins is not recommended during pregnancy whereas in the United States, they are recommended as a prophylactic measure. Their high molecular weight prevents their diffusion across the placental membrane and therefore prevents any fetal or neonatal risk. Bromocriptine is used as an inhibitor of lactation. During the post-partum period, serious accidents have been described: these consist of systemic hypertension, fits, infarcts (cardiac and neurological). It is contraindicated in case of systemic hypertension.
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PMID:[Drugs during preeclampsia. Fetal risks and pharmacology]. 2034 63

Food and Drug Administration (FDA) approved bromocriptine mesylate, a quick release formulation, 0.8 mg tablets, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Bromocriptine products were previously approved by the FDA for the treatment of pituitary tumors and Parkinson's disease. Bromocriptine is thought to act on circadian neuronal activities within the hypothalamus to reset abnormally elevated hypothalamic drive for increased plasma glucose, triglyceride, and free fatty acid levels in fasting and postprandial states in insulin-resistant patients. Adverse events most commonly reported in clinical trials of bromocriptine included nausea, fatigue, vomiting, headache, and dizziness. These events lasted a median of 14 days and were more likely to occur during initial titration of the drug. Due to novel mechanism of action, single daily dose, and lower incidence of stroke, myocardial infarction and vascular events, bromocriptine may act as landmark in treatment of type 2 diabetes.
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PMID:Bromocriptine mesylate: Food and Drug Administration approved new approach in therapy of non-insulin dependant diabetes mellitus with poor glycemic control. 2181 51


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