Bromocriptine toxicity

Eiythromycin markedly increases bromocriptine plasma levels, and a case of toxicity has been reported. Bromocriptine toxicity also occurred in a patient given josamycin. Clarithromycin increases cabeigoline levels, and erythromycin would be expected to interact similarly. Eiythromycin had no effect on lisuride levels. 

The acute toxicity of bromocriptine mesilate has been determined in the mouse as 230 and 2620 mg/kg i.v. and p.o., respectively. In the rabbit, the corresponding values were 12 and >1000 mg/kg (2). Thus, bromocriptine proved less toxic than the nonhydrogenated ergot alcaloids by one order of magnitude, resembling the behaviour of the dihydrogenated derivatives. 

At least as effective as bromocriptine in the treatment of advanced parkinsonian patients with levodopa-related motor fluctuations adverse effects similar in incidence and severity appears to lack some of the toxicity seen with bromocriptine, pergolide, and cabergoline (e.g., pleuropulmonary disease) may be a useful alternative in patients with intolerable adverse effects due to ergot derivatives... 

Bromocriptine and the ergot analogues suppress prolactin activity and amiodarone can cause iodine-induced hypo- or hyperthyroidism. Lithium, which has a low toxicity threshold, passes freely into milk and significant plasma concentrations may occur in nursing infants. 

Bromocriptine Inhibits adenylyl cyclase and interacts with other intracellular pathways Restores dopamine actions in the central nervous system Parkinson s disease, prolactinemia Oral Toxicity Nausea, headache, orthostatic hypotension... 

Bromocriptine Ergot derivative potent agonist at D2 receptors more toxic than pramipexole or ropinirole... 

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... 

BROMOCRIPTINE, CABERGOUNE ERYTHROMYCIN t bromocriptine and cabergoline levels Inhibition of metabolism Monitor BP closely and watch for early features of toxicity (nausea, headache, drowsiness)... 

Three Japanese women aged 78-87 years who had taken amantadine 100-200 mg/day for 1 month to 5 years, in two cases together with co-careldopa, developed multifocal myoclonus and two were confused (13). Amantadine concentrations were high in the two patients in whom they were measured, at over 3000 ng/ml a concentration over 1000 ng/ml is regarded as toxic. Amantadine was withdrawn and the myoclonus disappeared within 1-2 weeks and did not recur. Cortical myoclonus has also been described with levo-dopa and bromocriptine, but the mechanism is not known. 

Bromocriptine is the prototype but causes marked dyskinesias and CNS dysfunctions, including hallucinations, confusion, and psychosis. Formerly used as adjunct or alternative to lev-odopa, bromocriptine has been largely replaced by the non-ergots pramipexole and ropinirole, which are less toxic. However, they may cause sedation, including abrupt sleep onset. 

Prochlorperazine may antagonize the therapeutic effect of bromocriptine on prolactin secretion it also may decrease the vasoconstricting effects of high-dose dopamine and may decrease effectiveness and increase toxicity of levodopa (by dopamine blockade). Prochlorperazine may inhibit metabolism and increase toxicity of phenytoin. 

Toxicity Gastrointestinal effects include anorexia, nausea, and vomiting. Cardiovascular effects commonly include postural hypotension cardiac arrhythmias may also occur. Dyskinesias may occur with abnormal movements similar to those caused by levodopa. Behavioral effects include confusion, hallucinations, and delusions these occur more commonly with bromocriptine and pergolide than with levodopa. Like levodopa, bromocriptine and pergolide are contraindieated in patients with a history of psychosis. Miscellaneous ei ot-related effects with bromocriptine inelude pulmonary infiltrates and erythromelalgia. 

FTamipexole is an agonist at dopamine receptors and may have greater selectivity for D receptors in the striatum. It is not an ergot and appears to be less toxic than bromocriptine and pergolide. Pramipexole and ropinirole are often chosen for initial treatment of Parkinson s disease and sometimes have value in patients who have become refractory to levodopa. Side effects of these drugs include dyskinesias, postural hypotension, and somnolence. The answer is (E). 

Dopamine receptor agonist used in Parkinson s disease less toxicity than bromocriptine. Tox dyskinesias, sedation. Piamipexole is similar. 

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