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Cabergamoun
Prolactin enhances breast development during pregnancy and induces lactation. It is produced in the pituitary gland and its levels are normally inhibited by dopamine. Prolactin levels may be elevated in conditions like prolactinomas or certain drugs. Hyperprolactinemia can cause symptoms like menstrual irregularities, infertility, and galactorrhea. Prolactinomas are treated initially with dopamine agonists like cabergoline, which lower prolactin levels by activating D2 receptors on lactotroph cells. Cabergoline is more potent and long-acting than bromocriptine, making it a preferred treatment for conditions involving elevated prolactin levels.
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Cabergamoun
- 2. ProlactinProlactin Enhances breast developmentduring pregnancy, induces lactation & binds to specific receptors in the gonads Secretion is under tonic inhibitory control of dopamine, which acts via D2 receptors located on lactotrophs Production can be stimulated by thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) Normal level in women: less than 500 mIU/L (20 ng/ml or µg/l) Prolactin is down regulated by dopamine and is up regulated by estrogen
- 3. Prolactin LevelProlactin Level UnderlyingconditionUnderlying condition PRL levelPRL level Prolactinoma. Over 150 µg/L (five times higher than normal values) Psychoactive drugs, estrogen, functional (idiopathic) or microadenomas Values between normal and 100 µg/L Macroadenomas Over 250 µg/L In some cases over 1000 µg/L Normal PRL level Women: below 25 µg/L - Men: below 20 µg/L
- 4. Hyperprolactinaemia ManifestationsHyperprolactinaemia Manifestations InWomen: •Disruptions of normal menstrual period (oligomenorrhea / amenorrhea) •Hypogonadism, anovulation & Infertility In Men: •Signs of androgen deficiency and infertility (impotence, loss of libido, and rarely gynecomastia and galactorrhea) In both Sexes: •Galactorrhea •Tumor mass may cause visual-field defects or headache
- 5. Osteoporosis increased withelevated PRL due to estrogen lackOsteoporosis increased with elevated PRL due to estrogen lack If normal menses are present, osteoporosis does not occurIf normal menses are present, osteoporosis does not occur HyperprolactinemiaHyperprolactinemia How frequent is it?How frequent is it? Clinical symptoms Indicates elevated PRL in Galactorrhea 10% of women 99% of men Amenorrhea 15% Galactorrhea plus amenorrhea 75% Infertility 33% PCO 19-50 %
- 7. Hyperprolactinemia Mechanisms onHyperprolactinemiaMechanisms on Reproductive DysfunctionReproductive Dysfunction A.A. Inhibition of pulsatile GnRH secretion B.B. Interference with gonadotropin action in ovary C.C. Interference with estrogen positive feedback D.D. Inhibition of progesterone synthesis E.E. Impaired follicle development F.F. Inhibition of 5-alpha-reductase enzyme in men, thereby decreasing the conversion of testosterone to DHT
- 8. Hyperprolactinemia InhibitsHyperprolactinemia Inhibits progesteronesynthesis and Impairsprogesterone synthesis and Impairs follicle developmentfollicle development • Prolactin is involved in the induction of LH receptors to maintain progesterone synthesis. • Prolactin is necessary for complete lutenization. • Very high prolactin level in the early phase of follicular growth inhibit progesterone secretion. (J Endocrinol 64:555, 1975) • If prolactin exceeds 100 ng/mL, 100% of the follicles are atretic. (Nature 250:653 1974)
- 9. CabergamounCabergamoun cabergoline 0.5 mgtabcabergoline 0.5 mg tab More HopeMore Hope WithWith No MoreNo More SufferingSuffering
- 10. Composition Form Pharmacological action Preserved in Pack PRODUCTPROFILE : 0.5mg cabergoline : Scored tablets : Prolactin Inhibitor : PVC/PVDC strips : One strip of 2 tablets CabergamounCabergamoun
- 11. IS AN ERGOLINEDOPAMINE AGONIST WITH Agonist activity on D2 receptors in pituitary lactotrophs ------- Potent ------- ----- Selective ----- --- Long-lasting --- As compared to bromocriptine Cabergamoun is more potent in agonizing the D2 receptor and it occupied the receptor for longer CabergamounCabergamoun Prolactin is down regulated by dopamine ..
- 12. • Cabergamoun hasa potent and long-lasting PRL-lowering effect by direct stimulation of D2- receptors on lactotrophs • Cabergamoun at higher doses, has a central dopaminergic effect • Cabergamoun single oral administration of 0.25 - 1.5 mg, produces a significant decrease in serum PRL levels. CabergamounCabergamoun PharmacodynamicsPharmacodynamics
- 13. • Cabergamoun hasa prompt effect (within 3 hrs. from administration) and persists for - Up to 7 - 28 days in hyperprolactinemic patients - up to 14 - 21 days in puerperal women • Cabergamoun PRL-lowering effect is dose-related in terms of degree of effect and duration of action • Cabergamoun has a very selective action with no effect on basal secretion of other pituitary hormones or cortisol CabergamounCabergamoun PharmacodynamicsPharmacodynamics
- 14. CabergamounCabergamoun PharmacokineticsPharmacokinetics • Cabergamoun absorptionand disposition is not affected by food. • Cabergamoun is rapidly absorbed from the GIT with a peak in plasma between 0.5 and 4 hours • Cabergamoun is 41-42% bound to plasma proteins.
- 15. CabergamounCabergamoun PharmacokineticsPharmacokinetics • Cabergamoun eliminationhalf-life is long - 63-68 hours in healthy volunteers - 79-115 hours in hyperprolactinemic patients • Ten days after administration about 18% and 72% of the dose is recovered in urine and feces, respectively • Unchanged drug in urine accounted for 2-3% of the dose
- 16. CabergamounCabergamoun Therapeutic IndicationsTherapeutic Indications 1.Inhibition of physiological lactation 2. Suppression of already established lactation 3. Treatment of dysfunctions associated wit hyperprolactinaemia: “Amenorrhoea, oligomenorrhoea, anovulation, galactorrhea and infertility” 4. Prolactin-secreting pituitary adenomas (micro- & macroadenoma) 5. Idiopathic hyperprolactinaemia 6. Empty sella syndrome* with associated hyperprolactinaemia 7. Prevention of ovarian hyper-stimulation syndrome
- 17. CabergamounCabergamoun Dosage & AdministrationDosage& Administration
- 18. Indication Dose Inhibition oflactation 1mg (two tablets) given as a single dose on the first day after delivery Suppression of established lactation 0.25 mg (half a tablet) every 12 hours for 2 days (1 mg total dose) Amenorrhea, infertility & galactorrhea Initial dose is 0.5 mg per week Therapeutic dosage is usually 1 mg per week Prevention of OHSS One tablet daily for 8 days starting on the day of HCG injection CabergamounCabergamoun Dosage & AdministrationDosage & Administration Cabergamoun doses up to 4.5 mg per week have been used in hyperprolactinemic patients
- 19. CabergamounCabergamoun Normalizes PRL levelin patients with bromocriptine resistance or intolerance JCE&M 84(7): 2518-2522; 1999.
- 20. CabergamounCabergamoun Restores gonadal functionin women with hyperprolactinemic amenorrhea New Engl J Med. 331(14): 904-909; 1994. More HopeMore Hope WithWith No MoreNo More SufferingSuffering
- 21. CabergamounCabergamoun Is well toleratedby all patients More HopeMore Hope WithWith No MoreNo More SufferingSuffering New Engl J Med. 331(14): 904-909; 1994.
- 22. CabergamounCabergamoun Has better patienttolerability and compliance than bromocriptine Wang et al. Syatematic Reviews 2012, 1:33 “Treatment of hyperprolactinemia: a systematic review and meta-analysis” More HopeMore Hope WithWith No MoreNo More SufferingSuffering
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- 26. Management of PituitaryAdenomaManagement of Pituitary Adenoma Surgery If cabergoline is not successful, trans- sphenoidal surgery could be considered Radiation Observation Pharmacotherapy “Dopamine agonists are treatment of choice for most prolactinomas” Cabergoline is more effective than bromocriptine Liu, C, Tyrrell, JB. Successful treatment of a large macroprolactinoma with cabergoline during pregnancy. Pituitary 2001; 4:179.
- 27. Pharmacotherapy of ProlactinomaPharmacotherapyof Prolactinoma • First evidence of size reduction may occur after 6 weeks • Size reduction does not correlate with basal PRL or percentage reduction in PRL levels • In first 2-3 years, most will re-expand • After a few years, few re-expand
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- 30. Cabergamoun •Reduces the riskof OHSS in high-risk women •Dose: 0.5 mg (one tablet) daily0.5 mg (one tablet) daily •Duration: starting on the day of HCG injectionDuration: starting on the day of HCG injection andand continue for 8 dayscontinue for 8 days Cabergamoun in OHSSCabergamoun in OHSS
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- 32. Ovulatory dysfunction -PCOOvulatory dysfunction - PCO • 20% of all women on scan • Overweight, hirsute, oligomenorrhoea & acne • LH/FSH raised • Raised androgens • Mildly raised prolactin (in 19-50% of women with PCO - may be due to the high estrogen levels present in PCO)
- 33. Cabergamoun in PCOCabergamounin PCO Cabergamoun in hyperprolactinemia patients with PCO will: – Reduces testosterone and LH levels – Resumes ovulatory cycles.
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