Bromocriptinum

Bromocriptinum Uses, Dosage, Side Effects, Food Interaction and all others data.

Bromocriptinum mesilate is a nonhormonal, nonestrogenic agent that inhibits the secretion of prolactin in humans, with little or no effect on other pituitary hormones, except in patients with acromegaly, where it lowers elevated blood levels of growth hormone. Bromocriptinum mesilate is a dopamine receptor agonist, which activates post-synaptic dopamine receptors.The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor (thought to be dopamine); in the corpus striatum the dopaminergic neurons are involved in the control of motor function. Clinically, it significantly reduces plasma levels of prolactin in patients with physiologically elevated prolactin as well as in patients with hyperprolactinemia.

Bromocriptinum 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-receptors. It also exhibits agonist activity (in order of decreasing binding affinity) on 5-hydroxytryptamine (5-HT)1D, dopamine D3, 5-HT1A, 5-HT2A, 5-HT1B, and 5-HT2C receptors, antagonist activity on α2A-adrenergic, α2C, α2B, and dopamine D1 receptors, partial agonist activity at receptor 5-HT2B, and inactivates dopamine D4 and 5-HT7 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 making bromocriptine an effective agent for treating disorders associated with hypersecretion of prolactin. Pulmonary fibrosis may be associated bromocriptine’s agonist activity at 5-HT1B and 5-HT2B receptors.

Bromocriptinum
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Bromocriptinum
Availability	Prescription only
Generic	Bromocriptine
Bromocriptine Other Names	Bromocriptina, Bromocriptine, Bromocriptinum, Bromocryptine, Bromoergocriptine, Bromoergocryptine
Related Drugs	Farxiga, Gocovri, Rytary, Sinemet, Sinemet CR, metformin, Trulicity, ropinirole, pramipexole, Lantus
Type
Formula	C₃₂H₄₀BrN₅O₅
Weight	Average: 654.595 Monoisotopic: 653.221282062
Protein binding	90-96% bound to serum albumin
Groups	Approved, Investigational
Therapeutic Class	Antiparkinson drugs, Motility stimulants/Dopamine antagonist
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Hyperprolactinemia-Associated Dysfunctions: Dysfunctions associated with hyperprolactinemia including amenorrhea with or without galactorrhea, infertility or hypogonadism. Prolactin-secreting adenomasdn cases where adenectomy is elected, a course of bromocriptine mesilate therapy may be used to reduce the tumor mass prior to surgery.

Acromegaly Parkinson's Disease: Idiopathic or postencephalitic Parkinson's disease- As adjunctive treatment to levodopa (alone or with a peripheral decarboxylase inhibitor)

Bromocriptinum is also used to associated treatment for these conditions: Acromegaly, Parkinson's Disease (PD), Type 2 Diabetes Mellitus, Idiopathic hyperprolactinemic disorder, Neuroleptic malignant syndrome (NMS)

How Bromocriptinum works

The dopamine D₂ receptor is a 7-transmembrane G-protein coupled receptor associated with G_i proteins. In lactotrophs, stimulation of dopamine D₂ receptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca²⁺ from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine D₂ receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders.

Dosage

Bromocriptinum dosage

Hyperprolactinemia (Adult):

Initial: 1.25 mg to 2.5 mg orally daily.
Titration: Add 2.5 mg orally, as tolerated, to the treatment dosage every 2 to 7 days.
Maintenance: 2.5 mg to 15 mg orally daily.

Acromegaly (Adult):

Initial: 1.25 mg to 2.5 mg orally once daily, with food, at bedtime for 3 days.
Titration: Add 1.25 mg to 2.5 mg orally, as tolerated, to the treatment dosage every 3 to 7 days.
Maintenance: 20 mg to 30 mg orally daily
The maximum dosage should not exceed 100 mg/day.

Parkinson's Disease (Adult):

Initial: 1.25 mg twice daily with meals.
Titration: Add 2.5 mg/day, with meals, to dosage regimen every 14 to 28 days.
Maximum dosage: 100 mg/day.

Type 2 Diabetes (Adult):

Initial: 0.8 mg orally daily taken within two hours after waking in the morning with food
Titration: Increase by 0.8 mg weekly as tolerated
Maintenance: 1.6 to 4.8 mg orally daily taken within two hours after waking in the morning with food
The maximum dosage should not exceed 4.8 mg daily.

Hyperprolactinemia (11 to 15 years old):

Initial: 1.25 mg to 2.5 mg orally daily.
Maintenance: 2.5 mg to 10 mg orally daily.

Side Effects

Side effects in decreasing order of frequency are: nausea, headache, dizziness,fatigue, lightheadedness,vomiting .abdominal cramps,nasal congestion,constipation,diarrhea and drowsiness. A slight hypotensive effect may accompany treatment.The occurrence of adverse reactions may be lessened by temporarily reducing dosage to 0.5 mg. Abnormalities in laboratory tests may include elevations in blood urea nitrogen, SGOT, SGPT, GGPT, CPK, alkaline phosphatase and uric acid, which are usually transient and not of clinical significance.

Toxicity

Symptoms of overdosage include nausea, vomiting, and severe hypotension. The most common adverse effects include nausea, headache, vertigo, constipation, light-headedness, abdominal cramps, nasal congestion, diarrhea, and hypotension.

Interaction

Bromocriptinum may interact with dopamine antagonists, butyrophenones, and certain other agents. Compounds in these categories result in a decreased efficacy of Bromocriptinum: phenothi-azines, haloperidol, metodopramide, pimozide. Concomitant use of Bromocriptinum with other ergot alkaloids is not recommended.

Food Interaction

Avoid alcohol.
Take with food. Food reduces irritation.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Bromocriptinum Drug Interaction

Moderate: duloxetine, duloxetine, escitalopram, escitalopramUnknown: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, polyethylene glycol 3350, polyethylene glycol 3350, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, ondansetron, ondansetron

Bromocriptinum Disease Interaction

Major: cardiac disease, hypotension, psychoses/depression, psychosis

Elimination Route

Approximately 28% of the oral dose is absorbed; however due to a substantial first pass effect, only 6% of the oral dose reaches the systemic circulation unchanged. Bromocriptinum and its metabolites appear in the blood as early as 10 minutes following oral administration and peak plasma concentration are reached within 1-1.5 hours. Serum prolactin may be decreased within 2 hours or oral administration with a maximal effect achieved after 8 hours. Growth hormone concentrations in patients with acromegaly is reduced within 1-2 hours with a single oral dose of 2.5 mg and decreased growth hormone concentrations persist for at least 4-5 hours.

Half Life

2-8 hours

Elimination Route

Parent drug and metabolites are almost completely excreted via the liver, and only 6% eliminated via the kidney.

Pregnancy & Breastfeeding use

Pregnancy category B. Bromocriptinum should not be used during lactation in postpartum women.

Contraindication

Uncontrolled hypertension and sensitivity to any ergot alkaloids. In patients being treated for hyperprolactinemia Bromocriptinum mesilate should be withdrawn when pregnancy is diagnosed. Post partum period in women with a history of coronary artery disease & other severe cardiovascular conditions