DR. LEAL - ENDOCRINE DRUGS Flashcards
○ Autosomal dominant genetic disease
associated with growth failure, obesity, and carbohydrate intolerance.
○ GH treatment
decreases body fat
increases lean body mass, linear growth, and energy expenditure.
Prader-Willi Syndrome
shown to increase final height in girls with Turner syndrome by 10–15 cm (4–6 inches).
GH TREATMENT
● For treatment of severe IGF-I deficiency that is not
responsive to GH.
● Recombinant human IGF-I
● Adverse effect: hypoglycemia
MECASERMIN
Initial therapy of choice for GH-secreting adenomas
Endoscopic Transsphenoidal Surgery
reduce the production of GH.
Somatostatin analogs
dopamine receptor agonists
GH receptor antagonist;
prevents GH from activating GH signaling pathways.
PEGVISOMANT
reserved for patients
with inadequate response to surgical and medical therapies.
RADIATION THERAPY
○ 14-amino-acid peptide.
○ Found in the hypothalamus, parts of CNS,
pancreas, and other sites in the GIT.
○ Functions primarily as an
Inhibitory Paracrine Factor and
Inhibits the release of GH, TSH, glucagon, insulin, and gastrin.
○ Rapidly cleared from the circulation, with a half-life of 1-3 minutes.
○ Short duration of action.
SOMATOSTATIN
○ 14-amino-acid peptide.
○ Found in the hypothalamus, parts of CNS,
pancreas, and other sites in the GIT.
○ Functions primarily as an Inhibitory Paracrine Factor and Inhibits the release of GH, TSH, glucagon, insulin, and gastrin.
○ Rapidly cleared from the circulation, with a
half-life of 1-3 minutes.
○ Short duration of action.
SOMATOSTATIN
○ Somatostatin analog
○ 45x more potent than somatostatin in inhibiting GH release but only 2x as potent in reducing insulin secretion.
○ Reduced effect on pancreatic beta cells, hyperglycemia rarely occurs during treatment.
OCTREOTIDE
useful in localizing neuroendocrine tumors having somatostatin receptors
helps predict the response to octreotide therapy.
○ Useful for the acute control of bleeding from esophageal varices.
radiolabeled octreotide
Somatostatin analog
Approved for the treatment of acromegaly
Appears to have effects comparable to those of octreotide in reducing GH levels and normalizing IGF-I concentrations.
LANREOTIDE
GH receptor antagonist used to treat Acromegaly
Does not inhibit GH secretion and may lead to increased GH levels and possible adenoma growth
PEGVISOMANT
● Used in states of infertility to stimulate spermatogenesis in men and to induce follicle development and ovulation in women.
● Most common clinical use for controlled ovarian stimulation, which is the cornerstone of assisted reproductive technologies such as in vitro fertilization (IVF).
FSH, LH, AND HCG
● aka Human Menopausal Gonadotropin (hMG)
● Obtained from the urine of post-menopausal women.
● Partially broken down into FSH and LH in the body.
MENOTROPIN
○ Purified preparation of human FSH.
○ Extracted from the urine of postmenopausal women.
○ Withdrawn from the US market in 2015.
Urofollitropin (uFSH)
○ First and only recombinant form of human LH.
○ Withdrawn in 2012.
○ SQ injection: has a half-life of about 10 hours.
LUTROPIN ALFA
○ For stimulation of follicular development in
infertile hypogonadotropic hypogonadal women with profound LH deficiency (<1.2 IU/L).
○ May also be of benefit in certain subgroups of normogonadotropic women
Lutropin alfa with follitropin alfa
Produced by the human placenta and excreted into
the urine, hence it can be extracted and purified.
HUMAN CHORIONIC GONADOTROPIN
○ A recombinant form of hCG.
○ Purified from human urine.
○ Administered by SQ or IM injection.
○ Injection for those who want to get pregnant.
Choriogonadotropin alfa (rhCG)
○ Used to induce follicle development and ovulation in women with anovulation that is secondary to hypogonadotropic hypogonadism, polycystic ovary syndrome, and other causes.
○ Also used for controlled ovarian stimulation in assisted reproductive technology procedures.
GONADOTROPINS
○ Two primary risks of ovulation induction:
- Multiple pregnancies (twins or triplets)
- Ovarian hyperstimulation syndrome
GONADOTROPINS
required to stimulate the gonadotrophs to produce and release LH and FSH.
Pulsatile GnRH secretion
used to induce gonadal suppression in men with prostate cancer or children with central precocious puberty.
GnRH agonists
○ Use in controlled ovarian stimulation procedures.
○ Absorbed rapidly after subcutaneous injection.
○ 0.25 mg daily maintains GnRH antagonism.
○ Adverse effects: nausea and headache.
GANIRELIX
CETRORELIX
○ Advanced prostate cancer.
○ Initiation: 240 mg administered as two
subcutaneous injections.
○ Maintenance: 80 mg subcutaneous injection
every 28 days.
○ Adverse effects: androgen deprivation (hot
flushes and weight gain).
ABARELIX
DEGARELIX
● 198 amino acid peptide hormone.
● Structure resembles growth hormone.
● Principal hormone for lactation.
● Milk production is stimulated by prolactin when
appropriate circulating levels of estrogens,
progestins, corticosteroids, and insulin are present.
PROLACTIN
a result of hyperprolactinemia.
○ Infertility (inhibition of GnRH release).
○ Oligomenorrhea or amenorrhea, and
galactorrhea in premenopausal women.
○ Loss of libido, erectile dysfunction, and
infertility in men.
HYPOGONADISM
● Act in the pituitary to inhibit prolactin release.
● Standard first-line treatment for
hyperprolactinemia.
● Shrink pituitary prolactin-releasing tumors,
DOPAMINE AGONISTS
○ Ergot derivatives.
○ High affinity for dopamine D2 receptors.
● Bromocriptine and Cabergoline
○ Non-ergot agent.
○ High affinity for dopamine D2 receptors.
Quinagolide
○ Non-ergot D2 agonists used in Parkinson’s disease.
PRAMIPREXOLE
ROPINIROLE
○ Half-life: 65 hours
○ Longest duration of action.
○ Initiation at 0.25 mg twice weekly orally or
vaginally, can be increased gradually, according to serum prolactin determinations, up to a maximum of 1 mg twice weekly.
CABERGOLINE
○ Half-life: 7 hours
○ Safe to use during early pregnancy.
○ Used in Parkinson’s disease to improve motor function and reduce levodopa requirements.
○ Adverse effect: valvular heart disease.
○ Can reduce growth hormone release in
patients with acromegaly (not as effective)
BROMOCRIPTINE
● Stimulates muscular contractions in the uterus and myoepithelial contractions in the breast.
● Involved in parturition and the letdown of milk.
● During the 2nd half of pregnancy
● Administered IV for initiation and augmentation of labor.
OXYTOCIN
● Can be administered IM for control of postpartum bleeding.
● Stimulates the release of prostaglandins and leukotrienes that augment uterine contraction.
● Not bound to plasma proteins
OXYTOCIN
High concentrations of oxytocin with activation of vasopressin receptors
excessive fluid retention, or water intoxication, leading to hyponatremia, heart failure, seizures, and death.
Contraindications of OXYTOCIN
○ Fetal distress
○ Fetal malpresentation
○ Placental abruption
○ Predispositions for uterine rupture
○ Oxytocin receptor antagonist
○ Used in the treatment (tocolysis) for
preterm labor.
ATOSIBAN
● Also known as antidiuretic hormone, ADH
● Released by the posterior pituitary (see Figure 35) in response to rising plasma tonicity or falling blood pressure.
● Possesses antidiuretic and vasopressor
properties.
VASOPRESSIN
deficiency of Vasopressin
DIABETIC INSIPIDUS
Activates two subtypes of G protein-coupled receptors.
found on vascular smooth
muscle cells and mediate vasoconstriction via the
coupling protein Gq and phospholipase C.
V1 RECEPTORS
found on renal tubule cells and reduce diuresis through increased water permeability and water resorption in the collecting
tubules via Gs and adenylyl cyclase.
V2 RECEPTORS
● Treatments of choice for pituitary Diabetes Insipidus.
● Administered by IV or IM injection
● Vasopressin infusion is effective in some cases of
esophageal variceal bleeding and colonic
diverticular bleeding.
● High-dose vasopressin as a 40-unit IV bolus injection may be given to replace epinephrine in the Advanced Cardiovascular Life Support (ACLS) resuscitation protocol for pulseless arrest.
VASOPRESSIN AND DESMOPRESSIN
Overdosage can result in hyponatremia and seizures.
VASOPRESSIN AND DESMOPRESSIN
○ Also used for the treatment of
coagulopathy in hemophilia A and von
Willebrand disease
○ Can be administered intravenously,
subcutaneously, intranasally, or orally.
DESMOPRESSIN
ameliorates nocturnal enuresis by
decreasing nocturnal urine production.
Bedtime desmopressin therapy
VASOPRESSIN ANTAGONIST
High affinity for both V1a and V2 receptors.
CONIVAPTAN
VASOPRESSIN ANTAGONIST
○ 30-fold higher affinity for V2 than for V 1 receptors.
○ Treatment duration is limited to 30 days due to the risk of hepatotoxicity, including life-threatening liver failure.
TOLVAPTAN
