Bromocriptine : This synthetic ergot derivative 2bromoαergocryptine is a potent dopamine agonist; most of its actions are based on this property. It has greater action on D2 receptors, while at certain dopamine sites in the brain it acts as a partial agonist or antagonist of D1 receptor.
PROLACTIN INHIBITORS
Bromocriptine
This synthetic ergot
derivative 2bromoαergocryptine is a potent dopamine agonist; most of its actions
are based on this property. It has greater action on D2 receptors, while at
certain dopamine sites in the brain it acts as a partial agonist or antagonist
of D1 receptor. It is also a weak α adrenergic blocker but not an oxytocic.
Actions
1.
Decreases prolactin release from pituitary by
activating dopaminergic receptors on lactotrope cells—a strong
antigalactopoietic.
2.
Increases GH release in normal individuals,
but decreases the same from pituitary tumours that cause acromegaly.
3.
Has levodopa like actions in CNS—antiparkinsonian
and behavioral effects.
4.
Produces nausea and vomiting by stimulating
dopaminergic receptors in the CTZ.
5.
Hypotension—due to central suppression of
postural reflexes and weak peripheral α adrenergic blockade.
6.
Decreases gastrointestinal motility.
Pharmacokinetics
Only
1/3 of an oral dose of bromocriptine is
absorbed; bioavailability is further lowered by high first pass metabolism in
liver. Even then, it has higher oral: parenteral activity ratio than
ergotamine. Metabolites are excreted mainly in bile. Its plasma t½ is 3–6
hours.
PROCTINAL,
PARLODEL, SICRIPTIN, BROMOGEN 1.25 mg, 2.5 mg tabs.
Uses
Bromocriptine
should always be started at a low dose, 1.25 mg
BD and then gradually increased till response occurs otherwise side effects
become limiting.
1)
Hyperprolactinemia due to microprolactinomas causing
galactorrhoea, amenorrhoea and infertility in women; gynaecomastia, impotence
and sterility in men. Bromocriptine and cabergoline are the first line drug for
most cases. Relatively lower doses (bromocriptine 2.5–10 mg/ day or cabergoline
0.25–1.0 mg twice weekly) are effective. Response occurs in a few weeks and
serum prolactin levels fall to the normal range; many women conceive. Bromocriptine
should be stopped when pregnancy occurs, though no teratogenic effect is
reported. Most (60–75%) tumours show regression during therapy. However,
response is maintained only till the drug is given—recurrences occur on
stopping; lifelong maintenance therapy is needed.
2)
Acromegaly due to small pituitary tumours and inoperable cases. Relatively higher doses
are required (5–20 mg/day) and it is less effective than
somatostatin/octreotide. Oral administration and lower cost are the
advantages..
3)
Parkinsonism Bromocriptine, if used alone, is effective only at high doses (20–80 mg/day)
which produce marked side effects. However, response is similar to that of
levodopa. It is now recommended in low dose only, as an adjunct to levodopa in
patients not adequately benefited and in those showing marked ‘onoff’ effect.
4)
Hepatic coma: Bromocriptine may cause arousal.
5)
Bromocriptine suppresses lactation and breast
engorgement in case of neonatal death, but not recommended due to unfavourable
risk: benefit ratio.
Side Effects: Side effects are frequent and dose related.
Early: Nausea, vomiting,
constipation, nasal blockage.
Postural hypotension may be marked at initiation of therapy—syncope may occur
if starting dose is high. Hypotension is more likely in patients taking
antihypertensives.
Late: Behavioral
alterations, mental confusion, hallucinations,
psychosis—are more prominent than with levodopa.
Abnormal
movements, livedo reticularis.
Cabergoline
It is a newer D2 agonist;
more potent; more D2 selective and longer acting (t½ > 60 days) than
bromocriptine; needs to be given only twice weekly. Incidence of nausea and
vomiting is also lower; some patients not tolerating or not responding to
bromocriptine have been successfully treated with cabergoline. It is being
preferred for treatment of hyperprolactinemia and acromegali.
Dose: Start with 0.25 mg twice weekly; if needed
increase after every 4–8 weeks to
max. of 1 mg twice weekly.
CABERLIN
0.5 mg tab, CAMFORTE 0.5, 1 mg tabs.
Pergolide and Quinagolide are other D2 agonists
effective in hyperprolactinemia.
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