Cabergoline Uses, Side Effects, and More

 Cabergoline 

Brand name:- Caberlin 0.5mg tab, Comforter 0.5, 1mg tabs.

Cabergoline is a dopamine receptor agonist used for the treatment of hyperprolactinemic conditions due to various causes. It is a newer D2 agonist; more potent; more D2 selective and longer acting (t½ >60 hours) than bromocriptine ; needs to be given only twice weekly.  

Pharmacodynamic:-

Cabergoline stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits: agonist activity (in order of decreasing binding affinities) on 5-hydroxytryptamine (5-HT)2B, 5-HT2A, 5-HT1D, dopamine D4, 5-HT1A, dopamine D1, 5-HT1B and 5-HT2C receptors and antagonist activity on α2B, α2A, and α2C receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. 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. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion.

Pharmacokinetics:- 

Following a single oral dose, resorption of cabergoline from the gastrointestinal (GI) tract is highly variable, typically occurring within 0.5 to 4 hours. Ingestion with food does not alter its absorption rate. Human bioavailability has not been determined since the drug is intended for oral use only. In mice and rats the absolute bioavailability has been determined to be 30 and 63 percent, respectively. Cabergoline is rapidly and extensively metabolized in the liver and excreted in bile and to a lesser extent in urine. All metabolites are less active than the parental drug or inactive altogether. The human elimination half-life is estimated to be 63 to 68 hours in patients with Parkinson's disease and 79 to 115 hours in patients with pituitary tumors. Average elimination half-life is 80 hours.

The therapeutic effect in treatment of hyperprolactinemia will typically persist for at least 4 weeks after cessation of treatment.

 Mechanism of action:- 

The secretion of prolactin by the anterior pituitary is mainly

under hypothalamic inhibitory control, likely exerted through release of dopamine by

tuberoinfundibular neurons. Cabergoline is a long-acting dopamine receptor agonist with

a high affinity for D2 receptors. Results of in vitro studies demonstrate that cabergoline

exerts a direct inhibitory effect on the secretion of prolactin by rat pituitary lactotrophs.

Cabergoline decreased serum prolactin levels in reserpinized rats. Receptor-binding

studies indicate that cabergoline has low affinity for dopamine D1, α1- and α2-adrenergic,

and 5-HT1- and 5-HT2-serotonin receptors.

Used:- 

used to treat high levels of prolactin hormone in your body. High levels of prolactin in women can cause symptoms such as unwanted breast milk and missed periods and can cause difficulty becoming pregnant. High levels of prolactin in men can cause symptoms such as enlarged breasts and decreased sexual ability/desire. Cabergoline is an ergot medication and works by blocking the release of prolactin from the pituitary gland.

side effects:- 

Nausea, vomiting, stomach upset, constipation, dizziness, lightheadedness, or tiredness may occur.

Dose:-  Start with 0.25 mg twice weekly; if needed increase after every 4-8 weeks to max . Of 1 mg twice weekly.