Bromocriptine, administration effects

Cerebrospinal fluid rhinorrhea has been described as an interesting but highly unusual sequel of bromocriptine administration (SEDA-8, 143). The reverse effect, air aspiration through a sellar-pharyngeal leak, has also been encountered (SEDA-9,126). 

Six patients with Parkinson s disease were withdrawn from their antiparkinsonian medications (L-DOPA/carbidopa, bromocriptine, or lisuride) (Rabey et al. 1992, 1993). After 12 hours off medication, the subjects ate 250 g of cooked fava beans. Significant improvements in motor symptoms were noted, comparable to those seen with 125 mg of L-DOPA and 12.5 mg of carbidopa. In fact, three subjects developed severe dyskinesias after fava ingestion, akin to those seen after larger doses of pharmaceutical L-DOPA. Plasma levels of L-DOPA increased after fava ingestion in a manner comparable to that seen with administration of oral L-DOPA. These results suggest that the L-DOPA contained in fava beans was transported into the CNS and converted to dopamine. In five nonparkinsonian, healthy volunteers, a similar increase in plasma L-DOPA was observed after fava ingestion, although much lower. The difference in plasma L-DOPA between normal volunteers and parkinsonian patients is apparently due to a residual effect of carbidopa in the subjects with Parkinson s disease. Without carbidopa, the L-DOPA from fava is rapidly converted to dopamine in the blood stream and never crosses the blood-brain barrier. 

Consistent with earlier studies, Muscat et al. ( 58) reported on chronic exposure to mild unpredictable stress in rats as a model to study the antidepressant-reversible decreases in the consumption of palatable sweets. Using this model, they found that certain dopamine agonists (i.e., quinpirole, bromocriptine) administered intermittently had the same positive effects as TCAs. They further postulated that the infrequent, intermittent administration of dopamine agonists (e.g., psychostimulants) may avoid problems with tolerance and abuse while providing a clinically relevant antidepressant strategy. A report by Kapur and Mann ( 59) comprehensively reviews the role of dopamine in depressive disorders. They discuss several lines of evidence, including the following ... 

The effects of DA receptor agonists on cocaine self-administration have been examined, with some success—bromocriptine, lisuride, and SDZ 208911 have been reported to lower intravenous self-administration of cocaine (Pulvirenti and Koob 1994). 

The rapid (i.e. less than 4 h) activation of TH in the median eminence by prolactin that constitutes the tonic component of prolactin stimulation does not require protein synthesis, but is probably associated with effects on the catalytic properties of this enzyme. Pasqualini and coworkers (1994) demonstrated in vitro that prolactin acts directly on TH in the mediobasal hypothalamus to trigger the phosphorylation of this enzyme. This effect, possibly mediated by protein kinase C, makes the enzyme less susceptible to inhibition by newly synthesized DA. That is, prolactin-induced short-term activation of TH results from the removal of end-product inhibition of the enzyme. Conversely, the acute reduction in TH activity measured in vitro in median eminence removed from rats 4 h after administration of bromocriptine is prevented by the coadministration of prolactin (Arbogast and Voogt, 1995). This can also be prevented by an inhibitor of phosphoprotein phosphatases, suggesting that rapid suppression of TH activity secondary to the bromocriptine-induced hypoprolactinemia may also result from dephosphorylation of the enzyme. 

Bromocriptine Therapy of hyperprolactinemia Oral tablet and vaginal suppository Proved to be effective and safe, without the adverse effects of oral administration vaginal suppository obtained higher reduction in serum prolactin 330... 

Bromocriptine is also available as an oral formulation, but oral administration to horses has not been reported. This drug should not be used in pregnant or lactating animals because of its effects on prolactin and lactation. Concomitant administration of bromocriptine and the phenothiazine tranquilizers or reserpine is contraindicated. 

All basic and advanced life-support measures should be implemented. Gastric decontamination should be performed. Butyrophenones are readily absorbed by activated charcoal. Aggressive supportive care should be instituted. Dystonic reactions respond well to intravenous benztropine or diphenhydramine. Oral therapy with diphenhydramine or benztropine should be continued for 2 days to prevent recurrence of the dystonic reaction. For patients suffering from neuroleptic malignant syndrome, a potentially fatal condition associated with the administration of antipsychotic drugs, dantrolene sodium, and bromocriptine have been used in conjunction with cooling and other supportive measures. Arrhythmias should be treated with lidocaine or phenytoin. Diazepam is the drug of choice for seizures phenytoin is used to prevent recurrence. Hemodialysis and hemoperfu-sion have not been shown to be effective. 

Bromocriptine was the first D2-receptor agonist to be used in the treatment of hyperprolactinemia and has been the mainstay of therapy for over 20 years. It inhibits the release of prolactin by directly stimulating postsynaptic dopamine receptors in the hypothalamus. Hypothalamic release of dopamine (prolactin-inhibitory hormone) inhibits the release of prolactin. Decreases in serum prolactin concentrations occur within 2 hours of oral administration with maximal suppression occurring after 8 hours, and suppressive effects persisting for up to 24 hours. Medical therapy with bromocriptine normalizes prolactin serum concentrations, restores gonadotropin production, and shrinks tumor size in approximately 90% of patients with prolactinomas. ... 

F. Prolactin-Inhibiting Hormone (PIH, Dopamine) Dopamine is the physiologic inhibitor of prolactin release. Because of its peripheral effects and the need for parenteral administration, dopamine is not useful in the control of hyperprolactinemia, but bromocriptine and other orally active ergot derivatives (eg, cabergoline. pergolide) are effective in reducing prolactin secretion from the normal gland as well as from pituitary tumors. 

In an in vitro system that generated HO from FeS04-H202, bromocriptine dose-dependently (IC50 = 11.25 0.89x 10" M) quenched HO radicals, but did not inhibit their formation (Ogawa et al. 1994). Pre-treatment with bromocriptine (5mg/kg, i.p., 7 days) completely protected against the decrease in mouse striatal dopamine and its metabolites induced by intraventricular injection of 6-hydroxy-dopamine (40 pg) after intraperitoneal administration of desipramine (25 mg/kg, administered i.p. 30 min after the final injection to block noradrenaline re-uptake sites), but similar pre-treatment with L-DOPA/carbidopa (75/7.5 mg/kg, i.p, 7 days) showed only partial protective effect. 

---