Bromocriptine, a peptide ergot alkaloid, is a specific central dopamine receptor agonist that excites postsynaptic dopamine receptors. It agonizes D2 receptors at normal doses and exerts anti-tremor paralysis effects; at low doses, it agonizes D3 receptors in presynaptic membrane and reduces dopamine release, which can be used to treat Huntington’s chorea. It agonizes dopamine receptors in pituitary cells, resulting in a decrease in the release of prolactin and growth hormone from the pituitary gland.
It is rapidly absorbed orally, but its absorption is incomplete, only 28%, due to the first shutdown effect in the liver. The Tmax after administration is 1-3 hours. Binding rate with plasma protein is 96%. The serum half-life is about 3 hours and the efficacy is maintained for about 14 hours. There are large individual differences after oral administration of this product. Almost all of oral bromocriptine is metabolized or eliminated by liver, about 90% is excreted by biliary tract and only 2% is excreted by urine.
I. Indications
1.Treatment of tremor palsy: Bromocriptine is a central dopamine receptor stimulant, which can directly excite the dopamine receptors in the extrapyramidal system, and is effective in the treatment of tremor palsy, with long half-life, long maintenance of efficacy and low drug resistance. It is effective in severe patients with rigidity and hyperkinesia, and can significantly reduce the “switching” phenomenon and dyskinesia caused by levodopa when used in combination with levodopa.
2, treatment of chronic schizophrenia and mania: chronic schizophrenia, especially the psychopathological basis of mainly negative symptoms, is the result of reduced dopamine function. Bromocriptine is a central dopamine receptor stimulant, which can enhance the activity of dopamine receptors, so it is effective.
3.Treatment of depression: bromocriptine is effective for depression by enhancing the activity of dopaminergic neurons. Bromocriptine is used to treat depressive mental abnormalities with good effect.
4.Treatment of antipsychotic malignant syndrome: This syndrome is a serious complication in antipsychotic drug treatment. Bromocriptine has good effect on it. At present, it is advocated that bromocriptine should be combined with antipsychotic drugs for the prevention of patients who need antipsychotic treatment and are prone to antipsychotic malignant syndrome.
5.Treatment of cocaine withdrawal syndrome: Bromocriptine can effectively reduce the anxiety symptoms of cocaine addiction and withdrawal.
6.Treatment of hyperprolactinemia and prolactinoma: The efficacy of bromocriptine in the treatment of prolactinoma is extremely significant, with an efficiency rate of 80%-90%.
7.Pre-operative preparation and post-operative treatment of prolactinoma: The treatment of large prolactinoma by radiation and surgery can be supplemented with oral bromocriptine to obtain more satisfactory results, which can shrink the adenoma and improve the pituitary function.
8.Used for milk withdrawal: Bromocriptine is effective for milk withdrawal because it can inhibit postpartum lactogen secretion.
9.Used for non-functional pituitary tumor: patients with non-functional pituitary tumor who have contraindications to surgery and radiotherapy can use bromocriptine.
10.Treatment of male hypogonadism: bromocriptine is effective for male breast development, impotence and semen deficiency.
11.Treatment of women infertility: Bromocriptine is effective in women infertility caused by hyperprolactinemia. The pregnancy rate can reach 37.5%-81% after the use of the drug. The pregnancy rate is 70.3% for microadenoma and 37.5% for macroadenoma, and the rapid growth of prolactinoma during pregnancy can be effectively controlled. There are reports of 212 cases of infertility in women diagnosed with ovulation disorders treated with bromocriptine.
12.Treatment of menstrual disorders: menstrual disorders, dysmenorrhea and scanty menstruation are often related to excessive secretion of prolactin, and bromocriptine has certain effect on them by inhibiting the secretion of prolactin.
13.Treatment of premenstrual syndrome.
14.Treatment of polycystic ovary syndrome: Bromocriptine can make the fluctuation of luteinizing hormone in patients with this syndrome weaken significantly, decrease the level of serum testosterone, restore ovarian function, turn menstruation to normal, and stop the development of polycystic ovary.
15.Treatment of breast diseases: Bromocriptine is effective in restoring ovarian function and treating breast diseases, such as mastopathy, overflow, postpartum milk return and postpartum mastitis, by inhibiting secretion of lactogen and reducing its antagonistic effect on follicle maturation hormone.
16.Treatment of pituitary growth hormone tumor: The efficacy of bromocriptine on growth hormone (GH) tumor is 50%-80%. Under normal circumstances, bromocriptine can stimulate the hypothalamus and pituitary gland to secrete growth hormone, but for pituitary tumor with acromegaly, it inhibits the secretion of growth hormone through excitation of dopamine receptors on pituitary hormone cells and antagonism of 5-HT, so that the plasma growth hormone level drops significantly.
17.Treatment of acromegaly: Bromocriptine can inhibit the secretion of pituitary growth hormone and reduce the level of blood growth hormone, which has good effect on acromegaly, with an efficiency of 70%-92%. It can also improve or normalize the glucose tolerance of most patients and reduce the dose of insulin or oral hypoglycemic drugs.
18.Treatment of Cushing’s disease: Most of Cushing’s disease is caused by corticotropinoma, and a few are abnormal secretion of gonadotropin-releasing hormone (GRH) by hypothalamus. Bromocriptine can reduce corticotropin, so it can be used to treat Cushing’s disease, and its efficiency is 30%-40%.
19.Treatment of pituitary hyperthyroidism: mainly rely on surgical treatment. For those who are contraindicated to surgery, long-term treatment with anti-thyroid drugs plus bromocriptine can be used with satisfactory results. Bromocriptine is effective by inhibiting the release of thyrotropin from the anterior pituitary gland.
20.Treatment of diabetes mellitus: Bromocriptine is effective in type I and II diabetes mellitus and occult diabetes mellitus, the mechanism is unknown. After adding bromocriptine to type I diabetes, insulin dosage decreases, blood glucose control is smooth, and the natural remission rate is high.
21.Treatment of hepatic encephalopathy: bromocriptine can agonize postsynaptic dopamine receptors, strengthen nerve conduction, and increase cerebral blood flow and cerebral metabolism, which can effectively improve the clinical symptoms of hepatic encephalopathy.
22.Treatment of glaucoma: dopamine receptors are related to the control of intraocular pressure. Bromocriptine can agonize dopamine receptors and lower intraocular pressure and be used for the treatment of glaucoma.
23.Treatment of idiopathic edema: idiopathic edema occurs in women during their reproductive years. It is thought to be related to the function of the peripheral dopamine system. Bromocriptine can reduce the daily weight gain and rapidly reduce the difference between early and late weight. It improves self-conscious symptoms, increases urination, and decreases upright aldosterone secretion and aldosterone response to uprightness.
24.Other: Bromocriptine can be used to treat Huntington’s chorea, myasthenia gravis, glomerulonephritis, systemic lupus erythematosus, multiple sclerosis, autoimmune enterocolitis, functional uterine bleeding, pituitary corticotropinoma, Nelson syndrome, hypothalamic hypothyroidism, etc., but the efficacy is not exact.
II. Dosage
1.Treatment of tremor palsy: start with 0.625mg each time, 1-2 times a day, and add 0.625mg every 3-7 days; or 2.5mg/d, and add 2.5mg every week until 7.5-30mg/d, until the minimum dose for the best efficacy.
2.Treatment of chronic schizophrenia and mania: chronic schizophrenia: 2-2.5mg once a day. Small dose of bromocriptine (7.5mg daily) has certain efficacy in mania.
3.Treatment of depression: 5mg/d, gradually increase to 10-25mg/d after 1 week, treatment for 4 weeks, efficiency 76%.
4.Treatment of cocaine withdrawal syndrome: 0.625mg/d, 4 times a day. Withdrawal symptoms can be improved after the drug is used.
5.Treatment of hyperprolactinemia and prolactinoma: 1.25-2.5mg daily, divided into 3 times before bed and between meals, and then gradually increased to maintenance amount of 2.5mg each time, 2-3 times a day, generally not more than 15mg daily.
6. For non-functional pituitary tumor: 30-60mg a day, divided into oral doses. It can shrink the tumor after more than 1 year of medication.
7.Treatment of male hypogonadism: 5-10mg a day orally.
8.Treatment of female infertility: small dose, intermittent, short-term use, starting on the 5th day of menstruation, 1.25mg, twice a day; or 2.5mg, taken at bedtime; continuous use until the basal body temperature rises 3-7 days to stop the drug, the results of each case with an average of 2.7 cycles, pregnancy rate of 100%.
9, treatment of menstrual disorders: menstrual disorders, dysmenorrhea, menstrual scarcity, etc. Usage: 1.25-2.5mg orally each time, 2-3 times daily, but the relapse rate is very high after stopping the drug, up to 70%-80%.
10.Treatment of premenstrual syndrome: Usage: 1.25-2.5mg orally each time, 2-3 times daily, can be taken on the 14th day of the menstrual cycle until the onset of menstruation.
11.Treatment of breast diseases: Treatment of breast enlargement: Start taking the drug on the 5th day after menstruation until the next menstrual cycle, stopping for 4 days in between. For the first 3 days of the first week, 1.25mg twice a day, for the next 4 days, 1.25mg 3 times a day; for the first 3 days of the second week, 2.5mg twice a day, for the next 4 days 2.5mg 3 times a day. Maintain until the end of the cycle. Other diseases: 1.25-2.5mg per oral dose, 2-3 times a day. Mastitis needs to be combined with antibiotics.
12.Treatment of pituitary growth hormone tumor: 10-60mg orally daily.
13.Treatment of acromegaly: The usual dose starts with 1.25-2.5mg orally 4 times a day, and the maximum dose can reach 60mg a day. blood concentration of growth hormone should generally be measured every 3 months to determine the appropriate dosage. Bromocriptine has a slow onset of action in the treatment of this condition, and its maximum effect often takes 8-12 weeks to appear.
14.Treatment of polycystic ovary syndrome: Bromocriptine can significantly reduce the fluctuation of luteinizing hormone, lower the serum testosterone level, restore ovarian function, turn menstruation to normal, and stop the development of polycystic ovaries in patients with this syndrome.
15.Treatment of pituitary hyperthyroidism: the commonly used amount is 7.5mg daily.
16.Treatment of hepatic encephalopathy: start with 2.5mg a day orally, then increase by 2.5mg every 3 days until 15mg a day as maintenance dose. Generally use for more than 8 to 12 weeks.
17.Treatment of glaucoma: Use 0.01%-0.05% eye drops several times a day.
Adverse reactions
The main common adverse reactions are nausea, vomiting, anorexia, constipation, abdominal pain, headache, dizziness, fatigue and upright hypotension, hyperactivity, movement disorders and psychiatric symptoms, the incidence of 68%. Less common adverse reactions include dry mouth, blurred vision, diplopia, gastrointestinal bleeding, irritability, memory loss, personality abnormalities, erythema limbosum, Raynaud’s phenomenon, and cardiac arrhythmias. It mostly occurs at the beginning of treatment and at high doses. It can be reduced after continuous use, and also when taken with food. About 3% of the cases require discontinuation of the drug. In addition, long-term (more than 1 year) high dose (more than 22.5mg per day) application of bromocriptine can develop pulmonary and pleural fibrosis, the incidence of which is 2-3%, mostly seen in the elderly and smoking patients.
IV. Interaction
1.Bromocriptine can be used in combination with the following drugs
(1) Levodopa: The combination of the two drugs has a synergistic effect on the treatment of tremor paralysis, and can reduce the dosage of levodopa (the application of bromocriptine 10mg, need to reduce the dosage of levodopa by 12.5%). It can reduce levodopa-induced “switching” phenomenon and involuntary movements, and prevent intra-day changes in symptoms. It can be used for patients with poor efficacy of levodopa.
(2) Insulin: Bromocriptine can enhance the efficacy of insulin in the treatment of diabetes, and can be used in combination to stabilize blood glucose control.
(3) Anti-thyroid drugs: Bromocriptine can inhibit the release of thyrotropin from the anterior pituitary gland, and its combination with anti-thyroid drugs can significantly enhance the efficacy of treatment of pituitary hyperthyroidism.
2.Bromocriptine should be avoided in combination with the following drugs
(1) phenothiazines, thiazides, butylphenols and antipsychotics: all of these drugs can significantly increase the serum prolactin concentration and counteract the anti-lactin secretion effect of bromocriptine. However, bromocriptine can be used to treat antipsychotic-induced overflow with good effect; it has synergistic effect when combined with haloperidol for the treatment of schizophrenia.
(2) Antihypertensive drugs: Combined use is likely to cause hypotension. Antihypertensive drugs such as reserpine and methyldopa can increase serum prolactin levels and counteract the anti-lactin secreting effect of bromocriptine.
(3) H2 receptor blockers: can significantly increase serum prolactin concentration, making bromocriptine less effective.
(4)Ashwagandha: The combination can reduce the effect of bromocriptine.
(5) Ethanol: Ethanol can enhance the adverse effects of bromocriptine. Bromocriptine also increases the sensitivity of patients to ethanol. Therefore, alcohol or drugs using alcohol as a solubilizer should be avoided during the application of bromocriptine therapy.
It is contraindicated in patients with a history of severe psychiatric disorders and myocardial infarction.