Does bromocriptine cause heart issues ?

[Mauritio]

This study included several thousand people and followed up with them after 10 years .The chance of developing valvualr heart disease was a tiny bit higher when on bromocriptine (0.34%) compared to the controll group which was 0.29%.
"Within 10 years of follow-up, 11 patients (0.34%, 95% CI 0.13-0.55%) and 44 controls (0.29%, 95% CI 0.20-0.37) met the primary endpoint of heart valve disease..."
- Incidence of heart valve disease in women treated with the ergot-derived dopamine agonist bromocriptine - PubMed


No significant findings even in cabergoline, bromocriptine was even safer than that.
"Mitral tenting area was significantly higher in CBG than in BRC and CTR. None of the valvar abnormalities was associated with symptoms. In conclusion, patients with prolactinomas treated with either CBG or BRC showed higher prevalence of trace and mild Tri or Mi regurgitation, but these findings were not clinically significant.
- A comparison of cabergoline and bromocriptine on the risk of valvular heart disease in patients with prolactinomas - PubMed

Not sure what the dosage was here unfortunetly.
"Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure."
- Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment - PubMed

There was a signficant association of bromocriptine ,especially in the higher dosages, although it was dose dependant. The mean daily dosage was 18.6mg!
I think that is way higher than what most people outside of parkinsons disease take and likely the reason for their clinical finding. This is corroborated by the fact that the study below alassociation so looked at PD-patients and found no to valvular heart disease. They used lower dosages.
"The development of mild and moderate-severe valvular heart disease in the bromocriptine group also showed a cumulative dose-response relationship. These results suggest that the higher the exposure to bromocriptine, the higher the risk of developing both mild and moderate-severe valvular regurgitations."

In this study they failed to find a correlation . The daily dosage was 8.5mg ,so more than twice as low as in the study above. So somehwheren between 8-18mg seems to be the cut-off dose for valvular heart disease when using bromocriptine. But as the authors said there has to be more research on that to be able to name the dosage more precicsely that causes issues.
"Our study failed to uncover definitive harmful effects of ergot derivative dopamine agonists on cardiac valves; this is considering the relatively lower daily doses than other reported cases. To establish a dosage dependency with valvulopathy, a more detailed study with higher doses of ergot derivatives for longer duration of treatment may be needed."
- Valvular heart disease in Parkinson's disease treated with ergot derivative dopamine agonists - PubMed

 

[Mauritio]

In low to medium doses it actually seems to "paradoxically" be heart protective ,which doctors have been surprised by when they give bromocriptine to type 2 diabetes patients (bromocriptine is actually approved for treating T2D)

"The composite CVD end point occurred in 16/1208 B-QR treated (1.3%) and 18/583 placebo treated (3.1%) subjects resulting in a 55% CVD hazard risk reduction..."
- Impact of bromocriptine-QR therapy on cardiovascular outcomes in type 2 diabetes mellitus subjects on metformin - PubMed

"CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined.

Results: Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95])."
- Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus - PubMed


This study is interesting because they looked at many different hormonal and metabolic markers and how they're affected by 3.2mg/ day.
There's a drastic change of the body away from inflammation ,which is always good.

Amongst others :
Noradrenaline :-33%
Prolactin: -42%
CRP: -45%
TLR4: -20%

- Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects - PubMed

 

[solomon]

In low to medium doses it actually seems to "paradoxically" be heart protective ,which doctors have been surprised by when they give bromocriptine to type 2 diabetes patients (bromocriptine is actually approved for treating T2D)

"The composite CVD end point occurred in 16/1208 B-QR treated (1.3%) and 18/583 placebo treated (3.1%) subjects resulting in a 55% CVD hazard risk reduction..."
- Impact of bromocriptine-QR therapy on cardiovascular outcomes in type 2 diabetes mellitus subjects on metformin - PubMed

"CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined.

Results: Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95])."
- Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus - PubMed


This study is interesting because they looked at many different hormonal and metabolic markers and how they're affected by 3.2mg/ day.
There's a drastic change of the body away from inflammation ,which is always good.

Amongst others :
Noradrenaline :-33%
Prolactin: -42%
CRP: -45%
TLR4: -20%

- Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects - PubMed

Intranasal route seem to lower the required dose to have similar effect compared to oral dose

Nasal spray vs oral administration of bromocriptine: pharmacology and effect on serum prolactin in puerperal women - PubMed

The oral administration of bromocriptine induces a variety of side-effects in about 50-70% of patients, the most common being nausea and vomiting, probably related to the local gastrointestinal effect of the drug. Nasal administration makes it possible to avoid intestinal and liver metabolism...

pubmed.ncbi.nlm.nih.gov

 

[Mauritio]

Intranasal route seem to lower the required dose to have similar effect compared to oral dose

Nasal spray vs oral administration of bromocriptine: pharmacology and effect on serum prolactin in puerperal women - PubMed

The oral administration of bromocriptine induces a variety of side-effects in about 50-70% of patients, the most common being nausea and vomiting, probably related to the local gastrointestinal effect of the drug. Nasal administration makes it possible to avoid intestinal and liver metabolism...

pubmed.ncbi.nlm.nih.gov

Interesting. Thanks for sharing.
You'd have to aquire bromocriptine as a nasal spray though. That might be tricky since it's already hard to source as an oral med.
Or you create your own nasal spray. Bromocriptine is only slightly water soluble though.

Maybe sublingual bromocriptine does make more sense , in terms of avoiding gastrointestinal side effects, saving money and avoiding first pass metabolism .

I think @NewACC was wondering about that recently ...

 

[solomon]

Interesting. Thanks for sharing.
You'd have to aquire bromocriptine as a nasal spray though. That might be tricky since it's already hard to source as an oral med.
Or you create your own nasal spray. Bromocriptine is only slightly water soluble though.

Maybe sublingual bromocriptine does make more sense , in terms of avoiding gastrointestinal side effects, saving money and avoiding first pass metabolism .

I think @NewACC was wondering about that recently ...

Agreed. sublingual with dissolved in alcohol might be better.

"The nasal formulation was prepared at the Department of Pharmaco-Chemistry, University of Bari, Italy, and consisted of bromocriptine dissolved in isopropyl alcohol 10 ml, propylene glycol 20 ml, water 30 ml, for a final bromocriptine concentration of 1.67 mg/ml. The components of the formulation were chosen on the basis of the need to ensure the complete solubility of the bromocriptine in order to allow controlled dosage and, on the other hand, to ensure the prolonged contact of the formulation with the nasal mucosa in order to improve absorption. As bromocriptine mesylate is poorly soluble in water (0.8 mg/ml), isopropyl alcohol was added to improve its aqueous solubility; in fact, the addition of 25% alcohol more than doubled the solubility. Propylene glycol was incorporated to enhance the viscosity of the solution and thus allow its more prolonged contact with the nasal mucosa; the addition of 30% glycol did not interfere with the spraying. The solution was sprayed intranasally by means of an appropriate dispenser at an administered dose of 2 spray doses per nostril (0.25 ml per nostril), corresponding to 0.8 mg of bromocriptine; the group receiving oral bromocriptine was given at the usual dose of 2.5 mg. After oral administration, bromocriptine is largely metabolized by the liver and less than 5% of the drug reaches the systemic circulation in an unmodified form (12); this means less than 0.125 mg in the case of the oral administration of bromocriptine 2.5 mg. Therefore, as a first attempt, 0.8 mg bromocriptine seemed to be an adequate dose for nasal administration"