Bromocriptine and other Dopaminergic Drugs

Dopaminergic drugs act by stimulating dopamine receptors.¹ These can be found in the brain in the substantia nigra area and also in the limbic system. It was originally thought that there were only two types of receptors, D1 and D2, but advances in molecular biology have led to the discovery of three more types.² It is hoped that research into the dopamine system will lead to developments in the management of schizophrenia, Huntingdon's disease, and many other conditions.^3,4 Dopaminergic drugs are either ergot-derived or non-ergot derived.

• Ergot-derived dopaminergic drugs include bromocriptine, cabergoline, and pergolide.
• Non-ergot drugs include pramipexole, ropinirole, and rotigotine.

• Hyperprolactinaemia - this is most frequently due to the presence of a micro- or macroprolactinoma in the pituitary gland. Dopaminergic drugs help to reduce tumour size and prolactin levels. Bromocriptine is well-established, safe and effective, but some patients are intolerant or resistant to therapy. Two newer drugs, cabergoline and quinagolide, are more effective and better tolerated.⁵
• Suppression of Lactation - this can be considered as 'physiological hyperprolactinaemia'. Bromocriptine and cabergoline are licensed for this use, but are not routinely recommended. Relief of postpartum pain and engorgement can usually be managed with simple analgesia and breast support. However, if further intervention is required, cabergoline is better tolerated. Quinagolide is not licensed for this indication.
• Cyclical benign breast disease/mastalgia - bromocriptine is licensed for this use, but, because of its adverse effects profile, is largely being superseded by low-dose tamoxifen or topical non-steroidal anti-inflammatories.⁶
• Acromegaly - dopaminergic drugs are being superseded as first-line therapy but still have a place as an adjunct in patients whose symptoms are not controlled by somatostatin analogues such as octreotide. They seem to be of value even in patients whose prolactin levels are normal.⁷ Cabergoline seems to be the most effective of the group for this indication.⁸
• Infertility - bromocriptine is used in patients with or without hyperprolactinaemia.
• Hypogonadism - about 80% of men and women with hypogonadotrophic hypogonadism and hyperprolactinaemia will respond to bromocriptine.⁹
• Galactorrhoea - dopaminergic drugs are first line therapy for galactorrhoea secondary to micro- or macroprolactinomas. Bromocriptine has the longest history for this indication and is safe and effective, although newer drugs such as quinagolide and cabergoline sometimes prove to be more effective and better tolerated.⁵
• Parkinson's Disease -
  • Dopaminergic drugs licensed for this use are bromocriptine, cabergoline, pergolide, pramipexole, ropinirole and apomorphine. The therapeutic window with this class of drugs is small, and NICE have demurred from recommending any specific first-line drug therapy. They advise that the choice of drug should be based on clinical and lifestyle preference and patient preference.
  • Due to adverse effects (see below) NICE guidance recommends that non-ergot drugs should be used in preference to ergot-derived drugs wherever possible.¹⁰ Dopaminergic drugs can be used as monotherapy in early Parkinson's. Dopamine agonists cause fewer motor complications than levodopa, but are less effective. Large trials are required to elucidate the place of dopamine agonists compared to levodopa in terms of quality of life and health economics outcomes (one such trial - the PD MED trial is currently in progress).¹¹
  • Dopamine agonists can be used as adjuvant therapy in later disease, combined with levodopa.¹⁰ Studies provide evidence that this combination reduces dyskinesia or motor fluctuations compared with levodopa alone. The addition of adjuvant therapy enables lower doses of levodopa to produce the same therapeutic effect.¹¹
  For further information see separate records on Dopamine-Receptor Agonists In Parkinson's Disease (see link further down the page) and Apomorphine for this indication.

Warnings for ergotamine-derived dopamine agonists such as pergoline and cabergoline concerning their association with fibrotic drug reactions and cardiovalvulopathy were first issued by the Medicines and Healthcare products Regulatory Agency (MHRA) in 2001. Further studies have confirmed that the risk is high and clinically significant. Ergot-derived dopamine agonists have consequently been relegated to second-line therapy for Parkinson's disease and should only be used if the patient is intolerant of non-ergot drugs or fails to improve on them.¹² The summaries of product characteristics for these drugs have been updated accordingly.*^13,14Among the important adverse effects of bromocriptine are sudden onset sleep and hypotension. Both effects are fairly uncommon, but the prescriber should be aware of them.¹⁵ More comprehensive details of adverse effects can be found in the drug monograph.

Ergot-derived dopaminergic drugs are contraindicated in patients with a history of pulmonary, pericardial, or retroperitoneal fibrotic disorders, or in those with anatomic evidence of cardiovalvulopathy.*¹²

NICE recommend that prior to using an ergot-derived agonist, patients should have renal function tests, ESR and chest radiograph, and annually thereafter.¹⁰

The recommendations of individual summaries of product characteristics are even more stringent. They recommend full cardiovascular assessment including echocardiogram prior to treatment.

During treatment particular attention should be paid to clinical signs and symptoms suggestive of renal insufficiency or ureteral/abdominal vascular obstruction, pleuro-pulmonary disease, or cardiac failure. An echocardiogram should be performed 3-6 months after initiation, and as clinically indicated thereafter, but not less than every 6-12 months.*^13,14

*For further details about adverse effects, contraindications and monitoring, see Dopamine-Receptor Agonists In Parkinson's Disease for details of the group as a whole, and individual drug monographs.