Endocrine Part II Flashcards
What controls the neuroendocrine system?
pituitary and hypothalamus
What kind of hormones are secreted by hypothalamus and pituitary
peptides or LMW proteins that bind to specific receptors
Hormones released by anterior pituitary are regulated by
neuropeptides that are called releasing or inhibiting factors
◦ They are produced in hypothalamus and reach pituitary via the hypophyseal portal circulation
◦ Each of the hypothalamic regulatory hormone controls the release of a specific hormone from the anterior pituitary
Hormones of anterior pituitary
💠ACTH [Corticotropin] 💠Growth Hormone [Somatotropin] 💠GnRH 💠Gonadatropins 💠Somatostatin [Growth hormone inhibiting hormone] 💠Prolactin
ACTH [Corticotropin]
Corticotropin releasing hormone [CRH] stimulates release of ACTH from pituitary
Its released in pulsatile fashion [most released in early AM & least in late evening]
Stress ↑ release of ACTH; cortisol ↓ its release
ACTH has limited medical use— mainly to help differentiate Addison’s disease from 20 adrenal failure [caused by a pituitary issue]
ACTH [Corticotropin] MOA
works in adrenal cortex to convert cholesterol to pregnenolone, which results in the synthesis of adrenal steroids and adrenal androgens
ACTH [Corticotropin] adverse effects
none with short term use; with longer use s/e similar to using steroids chronically
Growth Hormone [Somatotropin]
Growth hormone releasing hormone [GHRH] stimulates release of GH; its inhibited by Somatostatin
Released in pulsatile fashion, highest amounts while asleep
Amount of GH produced declines with age
This hormone stimulates cell proliferation, bone growth, lean muscle mass production, skin thickness and ↓ adiposity
Used to treat GH deficiency in children; growth failure in Prader- Willi, HIV wasting & adults with documented low GH; used off label as “antiaging” hormone
Somatotropin given SQ or IM; stimulates ILGF-1 in liver
Growth Hormone [Somatotropin] MOA:
GH effects exerted directly on its target organs, yet some effects mediated through insulin like growth factors 1 & 2
Growth Hormone [Somatotropin] Adverse effects:
edema, arthralgias, ↑ risk of DM
Growth Hormone [Somatotropin] Caution in children
children with closed epiphyses, those with diabetic eye disease, patients with Prader-Willi [see reference list] that are obese
Somatostatin [Growth hormone inhibiting hormone]
GHRH binds to receptors that suppress GH & TSH release; this hormone also suppress release of insulin, glucagon & gastrin
Hypothalamus releases GnRH in pulsed fashion to stimulate release of FSH & LH from anterior pituitary
Continuous release of GnRH [thru use of synthetic versions] causes down regulation of the receptors & inhibits release of the gonadatropins
synthetic version of Somatostatin [Growth hormone inhibiting hormone]
- Octerotide
- Lanreotide
depot injections given q4 weeks
◦ Used to treat acromegaly & s/e of carcinoid tumors
Somatostatin [Growth hormone inhibiting hormone] Adverse Effects
diarrhea, abdominal pain, gas, nausea & steatorrhea
GnRH
These agents used to ↓ production of gonadal steroids—androgen & estrogen
Prescribed for use in prostate cancer, endometriosis & precocious puberty
CI—pregnancy & lactation
Examples of GnRH
Leuprolide [Lupron]
Goserelin [Zoladex]
Nafarelin [Synarel]
Histrelin [Vantas]
Adverse Effects of GnRH
- in men, bone pain [initially], edema. gynecomastia, diminished libido, metabolic bone disease
- in women, hot flushes, sweating, decreased libido, depression & ovarian cysts
Gonadatropins
FSH/LH—these regulate our gonadal steroid production
◦ Used as prescriptions in infertility
hMG—obtained from urine of post menopausal women, contains both FSH & LH
◦ Can be used exogenously in fertility treatments
hCG—placental hormonal found in the urine of pregnant women
◦ Acts like LH in fertility therapies
Urofollitropin—FSH obtained from postmenopausal women that has no LH in it
Fertility Therapies for gonadatropins
◦ Follitropin [α & β]—human FSH products made by DNA recombinant technologies—for infertility
◦ Choriogonadotropin α—made by DNA recombinant therapy identical to hCG—used in fertility therapies
These are given IM over 5-12 days—the ovarian follicle grows & matures
A round of hCG follows— ovulation then occurs
Adverse effects of Gonadtropins
ovarian enlargement & possible hyperstimulation
Prolactin
◦ Stimulates & maintains lactation; yet it ↓ sexual
drive & reproductive functions
◦ Prolactin secretion is inhibited by dopamine acting at D2 receptors—Reglan [Metaclopromide] & all antipsychotics that act as dopamine ANTAGONISTS will increase the secretion of prolactin
◦ Hyperprolactinemia causes galactorrhea & hypogonadism
◦ For ↑ prolactin [not related to drugs], we prescribe Bromocriptine or Cabergoline
Posterior Pituitary
◦ These hormones are not regulated by regulator or releasing hormones—they are made in the hypothalamus, then transported to the posterior pituitary & released in response to specific physiological changes [such as ∆ in plasma osmolarity]
◦ If we administer these hormones—they are given IV
Hormones made by Posterior Pituitary
- oxytocin
2. vasopressin
Oxytocin
Used to stimulate uterine contraction & to induce labor
Also causes milk ejection by contracting myoepithelial cells around the mammary alveoli
Vasopressin releases what
ADH and Desmopressin [DDAVP]
ADH [Antidiuretic hormone]
◦ Has both antidiuretic & vasopressor effects
◦ In kidney it works to ↑ H2O permeability & reabsorption in collecting tubules
◦ Used to treat diabetes insipidus
◦ Can also be used in cardiac arrest & to ↓
bleeding in esophageal varices
◦ AE—H2O intoxication & low Na+
BMI for overweight
25-29.9
BMI for obese
30 or more
BMI for severe obesity
40 or more
Weight loss of ______% or more can result in…
↓ risk of Type 2 DM, metabolic syndrome & slowing prevalence of HTN and dyslipidemia [DLP]
Medication should be added when
Patient has a history of being unable to successfully lose weight & maintain weight loss AND
Meets indications for agents approved for long term management by FDA
◦ BMI >/= 27 with 1 or more weight associated complications [this is FDA language when drugs were approved, as you can see [slide #18]—recent guidelines suggest a lower BMI if patient has complications] OR
◦ BMI of >/= 30
Obesity medications can decrease weight loss by ____% within 6 months
5-10%
Obesity RX:
Anorexiants [oldest class]
◦ These are approved for short term use only [90
days]
◦ Diethylpropion [Tenuate] ◦ Phentermine [Adipex-P]
◦ Both of these agents ↑ norepinephrine [Phentermine also ↑ dopamine] & both inhibit the reuptake of NE [+/- Dp]; this ↑ in NE ↓appetite
Tolerance develops easily
Pharmacokinetics of Anorexiants [oldest class]
Phentermine is excreted in kidney; Diethylpropion is metabolized in the liver, the active metabolites are excreted in kidney—these metabolites have a 4-8 hour 1⁄2 life
Adverse effects of Anorexiants [oldest class]
controlled substances [S IV] b/c of potential for dependence; common SE—dry mouth, HA, insomnia, constipation; can ↑ BP
◦ Avoid in those with uncontrolled BP, CV disease, arrhythmias, CHF or stroke hx
Anorexiants contraindicated with
with other sympathomimetics [sudafed, excess caffeine, etc] & MAO inhibitors
Obesity RX:
Lipase inhibitor: Orlistat [Xenical/Alli]
◦ MOA—pentanoic acid ester that inhibits gastric and
pancreatic lipases, ↓ breakdown of fat
↓ fat absorption by 30%; main mechanism of weight loss—this loss of calories
◦ Pharmacokinetics—taken with food that contains fat; minimal absorption; excreted in feces
◦ AE—oily spotting, gas, interferes with absorption of fat soluble vitamins [A, E, D, K & β carotene]
◦ Separate use of vitamins by 20 & others agents by 40
◦ CI—pregnancy, chronic malabsorption, cholestasis
Obesity RX:
Serotonin Agonists:
Lorcaserin [Belviq]
◦ Selectively binds to 2C serotonin receptor [5-HT2c]
Previous drugs of this class caused valve disease— thought to be linked to their effect on 5-HT 2B receptors
◦ MOA—with 5HT-2c receptor activation, stimulates pro-opiomelanocortin neurons, which activate melanocortin receptors, causing a ↓ in appetite
◦ Pharmacokinetics—metabolized in liver—inactive metabolites are eliminated in the urine [not recommended in severe renal impairment]
Adverse effects of Lorcaserin [Belviq]
-nausea, headache, dry mouth, constipation, lethargy
◦ Rarely, mood changes and SI
◦ Caution with use of other serotonergic agent—
SNRIs, SSRIs, MAOIs—because of risk of NMS
◦ Monitor patient for development of valvular heart
disease—assess for new or ∆ in murmur
◦ Avoid prescribing this agent in patients with hx of
CHF, those with hx of known valve problems
Combination Drug:
Phentermine/Topiramate ER [Qsymia
◦ Because topiramate can be sedating, the stimulant
phentermine was added to counteract any sedation ◦ Dosed in stages & titrated ↑ over 2 weeks
MOA of Phentermine/Topiramate ER [Qsymia]
sympathomimetic combined with AED; true mechanism unclear, but thought to be ↑ satiety & ↓ appetite through augmented GABA activity
◦ CI—pregnancy, glaucoma, hyperthyroidism, active suicidal ideations, cannot be used within 14 days of taking an MAOI
Adverse Effects of Phentermine/Topiramate ER [Qsymia]
paresthesias, cognitive dysfunction, ↑ HR, diuretics that cause ↓ K+ can produce profound hypokalemia when given with Qsymia; can ↑ risk of renal stones [topiramate component] ; may ↓ efficacy of OCP
Combination Drug:
Naltexone ER/Bupropion ER [Contrave]
◦ For weight loss—exact MOA is unknown
Naltrexone antagonizes various opioid receptors, while Bupropion inhibits neuronal uptake of NE & dopamine
◦ CI—uncontrolled HTN, sz disorders, patients abruptly stopping ETOH, benzos, barbiturates or AEDs; patients on opioids
◦ AE—worsening depression, neuropsychiatric reactions; may need to ↓ dose of anti-diabetic agents; can ↑ levels of Paxil, Zoloft, Respirdol, Metoprolol
Liraglutide [Victoza or Saxenda] —High Dose
◦ 3 mg SQ daily
◦ MOA—GLP 1 receptor agonist; ↓ appetite & ↑ satiety
◦ CI—insulin, personal or family hx of thyroid cancers or mx endocrine neoplasia syndrome type 2, pancreatitis
◦ AE—constipation, diarrhea, dyspepsia, fatigue, increased HR, low BS [rare in nondiabetics], nausea
◦ Cannot administer 3 mg of Liraglutide as Victoza [must give 2 shots of 1.8 + 1.2 mg/ml]; but can give as one injection if you Rx patient with Saxenda
Drugs use for long term weight management
- Orlistat
- Lorcaserin
- Phentermine/Topiramate ER
- Naltraxone ER/Bupropion ER
- Liraglutide
Orlistat [Alli]
Drug class: none
Dosage:
120 mg TID
60 mg TID [otc dosing]
MOA: lipase inhibitor
Therapeutic effect: fat excretion in stool
Lorcaserin [Belviq]
Drug class: Schedule IV
Dosage: 10 mg BID
MOA: seratonin 2C receptor agonist
Therapeutic effect: appetite suppression
Phentermine/Topiramate ER [Qsymia]
Drug class: Schedule IV
Dosage:
7.5/46 mg QD [can increase to 15/92 mg QD if needed]
MOA: Sympatho- mimetic/AED
Therapeutic effect: Appetite suppression
Naltraxone ER/Bupropion ER [Contrave]
Drug class: none
Dosage: 16/180 mg BID
MOA:Opioid antagonist/anti- depressant
Therapeutic effect: Appetite regulation
Liraglutideb [Victoza/Saxenda]
Drug class: none
Dosage: SQ 3mg daily
MOA: GLP-1 receptor agonist
Therapeutic effect: appetite suppression
Cautions: Orlistat [Alli]
Other drugs: ↓ cyclosporine exposure
GI/Biliary: Cholestasis** Mal- absorption** Cholelitiasis High fat diets Must replace fat soluble vitamins
Renal/GU: Increased urine oxalate—use caution
Cautions: Lorcaserin [Belviq]
Caution with CV-Valvular heart dx seen with other seratonergic agents Priapism
CNS: Seratonin syndrome Cognitive impair- ment
Psych: Psychiatric disorders with super high doses May cause depression in some
Cautions: Phentermine/Topiramate ER [Qsymia]
Caution with other drugs- MAOI**
Caution with CV-increased HR
Caution with endocrine-Hyperthyroidism** Metabolic acidosis Low BS
Caution with reproductive- Fetal toxicities [oral clefts]
CNS-Cognitive impairment with rapid titration
Visual-glaucoma
Psych- AED may ↑ risk of SI
Mood & sleep disorders
Renal/GU-Increased creatinine—use caution
Cautions: Naltrexone ER/Bupropion ER Contrave
Caution with drugs-Other bupropion products, chronic** opioids, MAOI
Caution with CV-Uncontrolled HTN** Increases BP and HR
Caution with endocrine-Hypoglycemia
GI/Biliary- hepatotoxic
CNS-Seizures** Eating Disorder**
Seizure Risk
Visual-Angle closure glaucoma
Psych-BB warnings on Bupropion— increased risk of SI [especially in those <24 yrs]
Neuropsychiatric events have occurred when used for smoking cessation
Cautions: Liraglutide [high dose] Victoza/Saxenda
Caution with other drugs-insulin Caution with CV-increased HR Caution with endocrine-Personal or HF of thyroid cancer** Multi-endocrine neoplasia syndrome II** Hypoglycemia Type I DM DKA GI/Biliary- Acute GB disease HX of acute pancreatitis Psych- SI or suicidal behaviors Renal/GU- Renal impairment— use caution
Metabolic syndrome
is a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes. These conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels.
