ergot derivative with potent dopamine receptor agonist activity
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) reduces plasma levels of prolactin in patients with physiologically elevated prolactin as well as in patients with hyperprolactinemia. has little or no effect on other pituitary hormones, except in patients with acromegaly, where it lowers elevated blood levels of growth hormone in the majority of patients Pharmacokinetic profile Bromocriptine No affected by food T1/2 about 2.5- 5 hour 90%-96% bound to serum albumin Bromocriptine undergoes extensive first-pass biotransformation bromocriptine has a high affinity for CYP3A and hydroxylations at the proline ring Excreted mainly in feses Indication Hyperprolactinemia-Associated Dysfunctions including amenorrhea with or without galactorrhea, infertility or hypogonadism Acromegaly idiopathic or postencephalitic Parkinsons disease Contra Indication Hypersensitivity to bromocriptine uncontrolled hypertension and sensitivity to any ergot alkaloids pregnancy postpartum period in women with a history of coronary artery disease and other severe cardiovascular conditions Drug interaction alcohol may potentiate the side effects of bromocriptine interact with dopamine antagonists butyrophenones decreased efficacy of bromocriptine Bromocriptine is a substrate of CYP3A4. Caution should therefore be used when co administering drugs which are strong inhibitors of this enzyme (such as azole antimycotics, HIV protease inhibitors). macrolide antibiotics such as erythromycin can increase the plasma levels of bromocriptine bromocriptine and octreotide led to increased plasma levels of bromocriptine Adverse reaction nausea (49%), headache (19%), dizziness (17%), fatigue (7%), lightheadedness (5%) A slight hypotensive orthostatic/postural (6%) dry mouth/nasal stuffiness (4%) on-off phenomenon abnormal involuntary movements Abnormal blood urea nitrogen, SGOT, SGPT, GGPT, CPK, alkaline phosphatase and uric acid psychomotor agitation/excitation, seizures excess daytime somnolence, sudden onset of sleep visual disturbance, vision blurred tachycardia, pleurisy Leuprolide Leuprolide long-acting GnRH analog given by IM inj Mec of action : A synthetic analogue of luteinizing hormone releasing hormone (LHRH). Initially causes a transient increase in testosterone; however, with continuous administration, testosterone levels are decreased. Decreased testosterone levels and resultant decrease in spread of prostate cancer. Reduction of pain/lesions in endometriosis. Decreased growth of fibroids. Delayed puberty. Pharmacokinetic profile of Leuprolide The absorption of leuprolide was characterized by an initial increase in plasma concentration, with peak concentration ranging from 4.6 to 10.2 ng/mL at four hours postdosing leuprolide concentrations started to plateau within two days after dosing and remained relatively stable for about four to five weeks plasma concentrations of about 0.30 ng/mL. 43% to 49% binding to protein plasma T1/2 about 3 hr Excreted mainly via urine No drug interaction because leuprolide acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes and only about 46% bound to plasma proteins Indication Endometriosis (dose 3.75 mg IM) for 6 months Uterine Leiomyomata (Fibroids) (dose 3.75 mg IM) for 3 months + iron therapy Advanced prostate cancer in patients who are unable to tolerate orchiectomy or estrogen therapy Central precocious puberty (CPP) Contra Indication Hypersensitivity to GnRH, GnRH agonist analogs Undiagnosed abnormal vaginal bleeding Pregnant woman breast-feed woman Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions Markedly impaired liver function or liver disease Known or suspected carcinoma of the breast Adverse effect CNS: STROKE, dizziness, headache, seizures, syncope; EENT: blurred vision; Subcut, hearing disorder. Resp: hemoptysis CV: myocardial infarction, pulmonary emboli, angina, arrhythmias, QT interval prolongation, vasodilation Endo: breast swelling, breast tenderness, hyperglycemia GI: anorexia, diarrhea, dysphagia, nausea, vomiting, hepatotoxicity Drug interaction
increased antineoplastic effects with
antiandrogens, (megestrol, flutamide). Octreotide Overview exerts pharmacologic actions similar to the natural hormone, somatostatin more potent inhibitor of growth hormone, glucagon, and insulin than somatostatin also suppresses LH response to GnRH, decreases splanchnic blood flow, inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide Pharmacokinetic profile of Octreotide
After subcutaneous injection, octreotide is absorbed rapidly and
completely from the injection site peak concentrations of 5.2 ng/mL (100 mcg dose) were reached 0.4 hours after dosing 65% was bound in the plasma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin The elimination of octreotide from plasma had an apparent half-life of 1.7 to 1.9 hours compared with 1-3 minutes with the natural hormone mainly excreted via urine Indication
Acromegaly
Carcinoid tumor
Vasoactive Intestinal Peptide Tumors
(VIPomas) Contra Indication and warning Sensitivity to this drug or any of its components the majority of patients developing gallbladder abnormalities (inhibit gallbladder contractility and decrease bile secretion) Cardiac conduction abnormalities (QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, and early R wave progression) suppresses secretion of thyroid stimulating hormone hypothyroidism Depressed vitamin B12 levels Drug Interaction + cyclosporine : decrease blood levels of cyclosporine and result in transplant rejection Patients receiving insulin, oral hypoglycemic agents, beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may require dose adjustments of these therapeutic agents Somatropin Pharmacokinetic profile Recombinant human growth hormone (rhGH) The absolute bioavailability of recombinant human growth hormone (r-hGH) after subcutaneous administration ranges between 70-90% The mean half-life of intravenous somatropin in normal males is 0.6 hours, whereas subcutaneously and intramuscularly administered somatropin has a half-life of 1.75 and 3.4 hours The mean clearance of r-hGH 14.6 2.8 L/hr. Indication
the long-term treatment of children with growth
failure due to inadequate secretion of endogenous growth hormone
replacement of endogenous growth hormone in
adults with growth hormone deficiency Contra indication and warning pediatric patients with closed epiphyses patients with active proliferative or severe non-proliferative diabetic retinopathy active malignancy acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure Prader-Willi syndrome who are severely obese or have severe respiratory impairment Drug Interaction Somatropin inhibits 11-hydroxysteroid dehydrogenase type 1 (11HSD-1) in adipose/hepatic tissue and may significantly impact the metabolism of cortisol and cortisone Excessive glucocorticoid therapy may attenuate the growth promoting effects of somatropin in children In adult women on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal Adverse reaction Arthralgia Headache Influenza-like symptoms Edema peripheral Back pain Myalgia Rhinitis Upper respiratory tract infection Carpal tunnel syndrome THANK YOU