Bromocriptine dosing

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. 

Bromocriptine directly binds to the D2 receptors on the lac-totroph cells to exert its effect. Bromocriptine normalizes prolactin level, restores menstrual cycles, and reduces tumor size in approximately 90% of patients.49 Adverse effects such as nausea, dizziness, and orthostatic hypotension often limit 5% to 10% of patients from continuing treatment. Thus, start bromocriptine at a low dose (e.g., 0.625-1.25 mg) at bedtime... 

Bromocriptine (Parlodel ) 0.625-1.25 mg/day at bedtime 1.25 mg increments at 1 -week interval 2.5-1 5 mg/day 40 mg/day 2 to 3 divided doses per day Dizziness, headache, syncope, nausea, vomiting, Gl cramps, orthostatic hypotension ... 

Dackis C., Golf M., Sweeney D., Byron J., Climko R. Single dose bromocriptine reverses cocaine... 

It became known to suppress prolactine secretion, and it is therefore a useful tool in the treatment of prolactine dependent disorders, such as galactorrhea associated with hyperprolactinemia and postpartum, as well as certain kinds of sterility (3 - 9). In more elevated doses, the drug is a potent antiparkinsonicum. In addition, there is recent evidence of bromocriptine playing an important role in the trace heavy metals balance of the brain (10). 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

The well-known emetic effect of ergot alcaloids in dogs was particularly pronounced with bromocriptine, even with oral doses of as low as 0.1 mg/kg. 

The principal metabolites have been isolated from the bile of rats treated with high doses of bromocriptine. The structure of the isolated metabolites was elucidated by means of spectroscopic techniques. 

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. 

L-DOPA can be initiated at 50 mg taken at bedtime and increased stepwise over a few weeks until the symptoms are relieved. Bromocriptine can be initiated at 7.5 mg at bedtime, pramipexole is often dosed at 0.125-0.375 mg at night, and ropinirole, which has an indication for RLS, is typically administered at 0.25-3 mg at bedtime. These medications are not without side effects. They may cause nausea and, over time, insomnia. Less commonly, these medications can cause hallucinations or involuntary movements called dyskinesias. These side effects usually resolve rapidly upon discontinuing the medication. 

Administration of bromocriptine necessitates monitoring pituitary gland function, especially during pregnancy, whereas in psychotic disorders, including schizophrenia, bromocriptine must be administered with caution. There is no need to reduce the dose or administer bromocriptine with caution in patients with renal impairment. 

Bromocriptine (Parl el) [Antiparkinsonian Agent/Dopamine Receptor Agonist] Uses Parkin on Dz, hyperprolactinemia, acromegaly, pituitary tumors Action Direct-acting on the striatal dopamine receptors X prolactin secretion Dose Initial, 1.25 mg PO bid titrate to effect, w/ food Caution [B, ] Contra Severe ischemic heart Dz or PVD Disp Tabs, caps SE X BP, Raynaud phenomenon (vasospastic disorder resulting in discoloration of the fmgers/toes), dizziness, N, hallucinations Interactions T Effects W/ erythromycin, fluvoxamine, nefazodone, sympathomimetics, antihypertensives X effects W/ phenothiazines, antipsychotics EMS Monitor BP may cause intolerance to EtOH OD May cause NA, severe hypotension give IV fluids symptomatic and supportive... 

More potent with longer half-life than bromocriptine or pergolide, allowing for less frequent dosing... 

The involvement of dopaminergic neurotransmission in AD has led to the use of agonists such as bromocriptine, lisuride, and pergolide, with poor results. A selective monoamine oxidase B inhibitor (MAO-B) such as deprenyl has also been employed. Little solid information exists on the effects of deprenyl on AD. Unfortunately, all information available comes from small studies. In a double-blind study, Tariot et al. (1987) observed that, with a daily dose of 10 mg in 17 patients with AD, a significant reduction in the scores for anxiety, depression, tension, and excitement was achieved. Burke et al. (1993), in a study of more than 20 patients with AD during a period of 15 months, found no behavioral changes in the progression of the illness nor in its scores. 

B. Indications and use Sandostatin is indicated to reduce blood levels of growth hormone and IGF-I (somatomedin-C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, or bromocriptine mesylate at maximally tolerated doses. It is also indicated for the symptomatic treatment of patients with metastatic carcinoid tumors, where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease, and for the treatment of the profuse watery diarrhea associated with VIP (vasoactive intestinal peptide)-secreting tumors (vipomas). 

Bromocriptine, apomorphine, lisoride, and other direct-acting DA agonists benefit Parkinson s disease and can also cause psychotic reactions at high doses. 

The ergot alkaloids are variably absorbed from the gastrointestinal tract. The oral dose of ergotamine is about 10 times larger than the intramuscular dose, but the speed of absorption and peak blood levels after oral administration can be improved by administration with caffeine (see below). The amine alkaloids are also absorbed from the rectum and the buccal cavity and after administration by aerosol inhaler. Absorption after intramuscular injection is slow but usually reliable. Bromocriptine and cabergoline are well absorbed from the gastrointestinal tract. 

Bromocriptine is a D2 agonist its structure is shown in Table 16-6. This drug has been widely used to treat Parkinson s disease in the past, but is now rarely used for this purpose, having been superseded by the newer dopamine agonists. Bromocriptine is absorbed to a variable extent from the gastrointestinal tract peak plasma levels are reached within 1-2 hours after an oral dose. It is excreted in the bile and feces. The usual daily dose of bromocriptine for parkinsonism varies between 7.5 and 30 mg. To minimize adverse effects, the dose is built up slowly over 2 or 3 months from a starting level of 1.25 mg twice daily after meals the daily dose is then increased by 2.5 mg every 2 weeks, depending on the response or the development of adverse reactions. 

Postural hypotension may occur, particularly at the initiation of therapy. Painless digital vasospasm is a dose-related complication of long-term treatment with the ergot derivatives (bromocriptine or pergolide). When cardiac arrhythmias occur, they are an indication for discontinuing treatment. Peripheral edema is sometimes problematic. Cardiac valvulopathy may occur with pergolide. 

A dopamine agonist alone or in combination with pituitary surgery, radiation therapy, or octreotide administration can be used to treat acromegaly. The doses required are higher than those used to treat hyperprolactinemia. For example, patients with acromegaly require 20-30 mg/d of bromocriptine and seldom respond adequately to bromocriptine alone unless the pituitary tumor secretes prolactin as well as GH. 

Bromocriptine Activates dopamine D2 receptors Suppresses pituitary secretion of prolactin dopaminergic effects on CNS motor control and behavior Treatment of hyperprolactinemia and Parkinson s disease (see Chapter 28) Administered orally or vaginally Toxicity Gastrointestinal disturbances, orthostatic hypotension, headache, psychiatric disturbances, vasospasm and pulmonary infiltrates in high doses... 

Several lines of evidence show that dopamine (DA) is implicated in the mediation of some obsessive-compulsive behavior. Animal studies demonstrate that high doses of various dopaminergic agents, such as amphetamine, bromocriptine, apomorphine, and L-DOPA, induce stereotyped movements in animals, which resemble compulsive behaviors in OCD patients. Increased dopaminergic neurotransmission may be responsible for this. Human studies consistently report that abuse of stimulants such... 

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