Hypothalamic and Pituitary Drugs Flashcards
Corticotropin (ACTH) - MoA
Increased activity of cholesterol side-chain cleavage enzyme, causing conversion of cholesterol to pregnenolone. This stimulates of adrenal cortex to produce: cortisol, aldosterone, & androgens.
Corticotropin preparations
Porcine corticotropin
Cosyntropin
Corticorelin ovine triflutate
Cosyntropin - Classification
Synthetic form of human corticotropin
Cosyntropin - Clinical use
Diagnose Adrenal insufficiency (pituitary adenoma vs adrenal tumor)
Distunguish Congenital adrenal hyperplasia from ovarrian hyperandrogenism.
Why is cosyntropin used for diagnosing adrenal insufficiancy?
It increases cortisol levels in healthy individuals but fails to increase cortisol in persons with adrenal insufficiency
Corticorelin ovine triflutate - Classification and Administration
Corticotropin releasing hormone (CRH)
IV administration
Corticorelin ovine triflutate - Clinical use
Diagnostic test to determine the cause of excessive levels of cortisol in persons with Cushing syndrome
Growth hormone (Somatotropin) - MoA
Direct stimulation of lipolysis and antagonize insulin to elevate blood glucose levels
Indirect stimulation of insulin-like growth factor 1 (IGF-1): skeletal muscle growth, amino acid transport, protein synthesis, nucleic acid synthesis, cell proliferation.
Growth hormone preparations
Somatropin
Mecasermin
Somatropin - Classification and Administration
Recombinant form of somatotropin (GH)
Subcutaneous
Somatropin - Clinical use
GH deficiency in children: Idiopathic growth hormone deficiency Turner syndrome Chronic renal failure Prader-Willi syndrome
Somatropin - Contraindications
Malignancies, critically ill patients (increase mortality).
Which group of people are less responsive to somatropin?
Children who received craniospinal irradiation for treatment of childhood malignancy
Somatropin - Adverse effects
None are common
Psuedotumor cerebri Slipped capital femoral Epiphysis Progression of scoliosis Edema Hyperglycemia. Turner: otitis media Myalgias Arthralgia Carpal tunnel syndrome
Mecasermin - Classification
Recombinant human IGF-1
Mecasermin - MoA
IGF-1 mechanisms: skeletal muscle growth, amino acid transport, protein synthesis, nucleic acid synthesis, cell proliferation.
Mecasermin - Clinical use
Growth failure in children with severe IGF-1 deficiency, GH receptor mutation, antibodies to GH
Mecasermin is produced by which bacteria?
E. coli
Mecasermin - Adverse effects
Hypoglycemia
How can you prevent hypoglycemia with the use of Mecasermin?
By eating a meal or snack before or soon after the time of injection
Growth hormone inhibitors
Somatostatin
Octreotide
Lanreotide
Cabergoline
Somatostatin - MoA
Inhibits GH secretion and insulin secretion from pancreas
Somatostatin - Clinical use
Limited use: short duration of action and multiple effects on secretory systems
Octreotide - Classification and Administration
Somatostatin analogue
Subcutaneous
Octreotide - MoA
Suppresses secretion of:
Growth hormone
IGF-1
Serotonin
GI-peptides (gastrin, motilin, secretin, VIP)
Greater effect on GH than insulin secretion
Octreotide - Clinical use
Acromegaly.
Tumors secreting insulin, glucagon, gastrin, thryotropin, and vasoactive intestinal peptide
Carcinoid tumors secreting serotonin and kallikrein
Octreotide - Adverse effects
Nausea, vomiting, abdominal cramps, steatorrhea, gallstones
Arrhythmias (brady, disturb conduction). (Hyper)+ hypoglycemia Constipation Flatulence B12-def in long-term use.
Lanreotide - Classification and Administration
Cyclic octapeptide analogue of somatostatin
Deep subcutaneous
Lanreotide - Clinical use
Acromegaly
Cabergoline - Classification
Selective dopamine 2 agonist
Cabergoline - MoA
Reduce GH, IGF-1 and prolactin
Cabergoline - Clinical use
Acromegaly
Hyperprolactinemia
Parkinson
Growth hormone receptor antagonist
Pegvisomant
Pegvisomant - MoA
GH receptor antagonist in target tissue, reduces IGF-1 levels in dose-dependent manner
Pegvisomant - Clinical use
Acromegaly in patients resistant to somatostatin analogs
Improve symptoms of tissue swelling, arthralgia, headache, perspiration, fatigue
Pegvisomant - Adverse effects
Good safety profile
Elevation of liver enzymes (Should be monitored)
Gonadotropins
Menotropins Chorionic gonadotropin Choriogonadotropin alpha Follitropin alfa & beta Urofollitropin Lutropin alfa
Gonadotropins - MoA
FSH: ovarian follicle maturation, estrogen production, spermatogenesis
LH: follicle development, induces ovulation, testosterone production
Gonadotropins - Clinical use
Infertility in men and women
Hypogonadism (men)
Gonadotropins - Adverse effects
Ovarian hyperstimulation syndrome (acites, hydrothorax, hypovolemia, shock)
Multiple pregnancies
Headache, depression, edema.
Menotropins - Classification
Human menopausal gonadotropins (LH+FSH)
Chorionic gonadotropin - Classification
Human chorionic gonadotropin (Placental hCG)
Essentially identical to LH in structure and function
Chorionic gonadotropin - Clinical use
Cryptorchidism and hypogonadism (puberty): Testosterone production and descending of testes
Choriogonadotropin alpha - Classification
Recombinant hCG
Follitropin alfa and beta - Classification
Recombinant FSH
Urofollitropin - Classification
Highly purified FSH
Lutropin alfa - Classification
Recombinant LH
Lutropin alfa is used in combination with?
Follitropin
GnRH agonists
Histrelin Goserelin Leuprolide Nafarelin Triptorelin
GnRH agonists - MoA
Binds to G protein-coupled receptors (GnRH-receptors).
Pulsatile adm: stimulate release of FSH & LH from pituitary.
Continuous adm: Down-regulation of GnRH-receptors & decreased FSH & LH secretion.
GnRH agonists - Clinical use
Advanced prostate and breast cancer, endometriosis and uterine fibroids
Central precocious puberty
Suppress the premature estrogen-induced LH surge that would otherwise occur during the use of gonadotropins in the treatment of infertility
GnRH agonists - Contraindications
Pregnancy and breast-feeding
GnRH agonists - Adverse effects
Symptoms of menopause: Hot flashes Depression Decreased libido Vaginal dryness Generalized pain Ovarian cysts Osteoporosis (prolonged treatment)
Histrelin - Clinical use
Central precocious puberty (12 month subcutaneous implant)
Goserelin, Leuprolide - Clinical use and Administration
Advance prostate cancer, brest cancer, and endometriosis
Subcutaneous implant
Goserelin, Leuprolide - Special considerations
Should be given with testosterone antagonist (flutamide or bicalutamide) because of transient increase in testosterone levels when treatment of prostate cancer has begun
Nafarelin - Clinical use
Endometriosis in women
Central precocius puberty in children
GnRH antagonists
Ganirelix
Cetrorelix
Degarelix
GnRH antagonists - MoA
Competitive antagonists at GnRH receptors.
Dose-dependently inhibit the secretion of FSH and LH
GnRH antagonists - Contraindications
Pregnancy
GnRH antagonists - Adverse effects
Hypersensitivity Allergic reactions (anaphylaxis)
Ganirelix, Cetrorelix - Clinical use
Inhibit LH surges in women undergoing ovarian stimulation as an infertility treatment
Degarelix - Clinical use
Advanced prostate cancer: inhibitions of gonadotropin secretion and testosterone release
Prolactin inhibitors
Dopamine agonists:
Cabergoline
Bromocriptine
Prolactin inhibitors - Clinical use
Symptomatic treatment for hyperprolactinemia:
Galactorrhea, hypogonadism, infertility
Parkinson
Which prolactin inhibitor can be used for mixed growth hormone and prolactin-secreting pituitary adenoma?
Cabergoline
Prolactin inhibitors - Adverse effects
Most common:
Nausea
Headache
Dizziness
Psychiatric manifestations
Erythromelalgia
Posterior pituitary hormones
Oxytocin
Vasopressin
Oxytocin - MoA
Increased strength of uterine contractions and causes milk ejection by contracting myoepithelial cells that line the ducts of the breast
Oxytocin - Clinical use
Induce or enhance uterine contractions during labor (IV injection)
Postpartum uterine hemorrhage (IM injection)
Milk let-down (Nasal spray)
Oxytocin - Contraindications
Fetal distress
Abnormal fetal presentation
Prematurity
Cephalopelvic disproportion
Oxytocin - Adverse effects
Uncommon
Cardiac arrhythmias
CNS stimulation
Excessive uterine contractions
Hyponatremia
Vasopressin analogues
Desmopressin
Conivaptan
Tolvaptan
Vasopressin - MoA
V1 receptors in vascular smooth muscle: vasoconstriction
V2 receptors (renal) activated by production of cAMP: Increased water reabsorption (by insertion of aquaporins). Expands ECF volume, concentrates urine.
Desmopressin - MoA
More potent antidiuretic effect than ADH (V2), less vasoconstriction.
Stimulates the release of von Willebrand factor (vWF) and factor VIII in blood vessel walls
Desmopressin - Clinical use
Diabetes indipidus:
Prevent nocturnal urine production and enuresis.
Nocturnal enuresis in children
Von Willebrand disease
Hemophilia A
Control bleeding caused by esophageal varices or colonic diverticula
Desmopressin - Contraindication
Coronary artery disease because of vasoconstrictive effects
Conivaptan - MoA
V1+V2 receptor antagonist
Conivaptan - Clinical use
Euvolemic and hypovolemic hyponatremia in hospitalized patients
Tolvaptan - MoA
Selective V2 receptor antagonist
Tolvaptan - Clinical use
Clinically significant hypervolemic and euvolemic hyponatremia, including patients with heart failure, cirrhosis, and SIADH
