Cabergoline pharmacology

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    Posted May 26, 2016 by Admin

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Cabergoline pharmacology

Posted Mar 06, 2016 by Admin

Less than 4 of the dose was excreted unchanged in the urine. Half life The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK /ERK kinase phosphorylation.

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.

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.

Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK /ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition.

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.

Long term use of 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Unpublished data suggest cabergoline 0.25mg twice daily for 2 days is effective in suppressing established puerperal lactation in about 85 of women.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.

Identification Name Cabergoline Accession Number DB00248 (APRD 00836) Type. Small Molecule Groups Approved Description Cabergoline, an ergot derivative, is a long-acting dopamine agonist and prolactin inhibitor. It is used to treat hyperprolactinemic disorders and Parkinsonian Syndrome.

High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain.

The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin.

Volume of distribution Not Available Protein binding Moderately bound (40 to 42) to human plasma proteins in a concentration-independent manner. Metabolism Hepatic. Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond of the urea moiety.

May also be used to manage symptoms of Parkinsonian Syndrome as monotherapy during initial symptomatic management or as an adjunct to levodopa therapy during advanced stages of disease. Pharmacodynamics Cabergoline stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects.

Stimulation of dopamine D2 receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors.

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.