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Advanced Pharmacology > Endocrine Part II > Flashcards

Endocrine Part II Flashcards

1
Q

What controls the neuroendocrine system?

A

pituitary and hypothalamus

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2
Q

What kind of hormones are secreted by hypothalamus and pituitary

A

peptides or LMW proteins that bind to specific receptors

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3
Q

Hormones released by anterior pituitary are regulated by

A

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

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4
Q

Hormones of anterior pituitary

A 
💠ACTH [Corticotropin]
💠Growth Hormone [Somatotropin]
💠GnRH
💠Gonadatropins
💠Somatostatin [Growth hormone inhibiting hormone]
💠Prolactin
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5
Q

ACTH [Corticotropin]

A

 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]

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6
Q

ACTH [Corticotropin] MOA

A

works in adrenal cortex to convert cholesterol to pregnenolone, which results in the synthesis of adrenal steroids and adrenal androgens

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7
Q

ACTH [Corticotropin] adverse effects

A

none with short term use; with longer use s/e similar to using steroids chronically

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8
Q

Growth Hormone [Somatotropin]

A

 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

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9
Q

Growth Hormone [Somatotropin] MOA:

A

GH effects exerted directly on its target organs, yet some effects mediated through insulin like growth factors 1 & 2

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10
Q

Growth Hormone [Somatotropin] Adverse effects:

A

edema, arthralgias, ↑ risk of DM

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11
Q

Growth Hormone [Somatotropin] Caution in children

A

children with closed epiphyses, those with diabetic eye disease, patients with Prader-Willi [see reference list] that are obese

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12
Q

Somatostatin [Growth hormone inhibiting hormone]

A

 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

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13
Q

synthetic version of Somatostatin [Growth hormone inhibiting hormone]

A
  1. Octerotide
  2. Lanreotide
    depot injections given q4 weeks
    ◦ Used to treat acromegaly & s/e of carcinoid tumors
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14
Q

Somatostatin [Growth hormone inhibiting hormone] Adverse Effects

A

diarrhea, abdominal pain, gas, nausea & steatorrhea

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15
Q

GnRH

A

 These agents used to ↓ production of gonadal steroids—androgen & estrogen
 Prescribed for use in prostate cancer, endometriosis & precocious puberty
 CI—pregnancy & lactation

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16
Q

Examples of GnRH

A

 Leuprolide [Lupron]
 Goserelin [Zoladex]
 Nafarelin [Synarel]
 Histrelin [Vantas]

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17
Q

Adverse Effects of GnRH

A
  • in men, bone pain [initially], edema. gynecomastia, diminished libido, metabolic bone disease
  • in women, hot flushes, sweating, decreased libido, depression & ovarian cysts
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18
Q

Gonadatropins

A

 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

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19
Q

Fertility Therapies for gonadatropins

A

◦ 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

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20
Q

Adverse effects of Gonadtropins

A

ovarian enlargement & possible hyperstimulation

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21
Q

Prolactin

A

◦ 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

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22
Q

Posterior Pituitary

A

◦ 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

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23
Q

Hormones made by Posterior Pituitary

A
  1. oxytocin

2. vasopressin

24
Q

Oxytocin

A

 Used to stimulate uterine contraction & to induce labor

 Also causes milk ejection by contracting myoepithelial cells around the mammary alveoli

25
Q

Vasopressin releases what

A

ADH and Desmopressin [DDAVP]

26
Q

ADH [Antidiuretic hormone]

A

◦ 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+

27
Q

BMI for overweight

A

25-29.9

28
Q

BMI for obese

A

30 or more

29
Q

BMI for severe obesity

A

40 or more

30
Q

Weight loss of ______% or more can result in…

A

↓ risk of Type 2 DM, metabolic syndrome & slowing prevalence of HTN and dyslipidemia [DLP]

31
Q

Medication should be added when

A

 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

32
Q

Obesity medications can decrease weight loss by ____% within 6 months

A

5-10%

33
Q

Obesity RX:

Anorexiants [oldest class]

A

◦ 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

34
Q

Pharmacokinetics of Anorexiants [oldest class]

A

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

35
Q

Adverse effects of Anorexiants [oldest class]

A

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

36
Q

Anorexiants contraindicated with

A

with other sympathomimetics [sudafed, excess caffeine, etc] & MAO inhibitors

37
Q

Obesity RX:

Lipase inhibitor: Orlistat [Xenical/Alli]

A

◦ 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

38
Q

Obesity RX:
Serotonin Agonists:
Lorcaserin [Belviq]

A

◦ 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]

39
Q

Adverse effects of Lorcaserin [Belviq]

A

-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

40
Q

Combination Drug:

Phentermine/Topiramate ER [Qsymia

A

◦ Because topiramate can be sedating, the stimulant

phentermine was added to counteract any sedation ◦ Dosed in stages & titrated ↑ over 2 weeks

41
Q

MOA of Phentermine/Topiramate ER [Qsymia]

A

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

42
Q

Adverse Effects of Phentermine/Topiramate ER [Qsymia]

A

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

43
Q

Combination Drug:

Naltexone ER/Bupropion ER [Contrave]

A

◦ 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

44
Q

Liraglutide [Victoza or Saxenda] —High Dose

A

◦ 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

45
Q

Drugs use for long term weight management

A
  1. Orlistat
  2. Lorcaserin
  3. Phentermine/Topiramate ER
  4. Naltraxone ER/Bupropion ER
  5. Liraglutide
46
Q

Orlistat [Alli]

A

Drug class: none

Dosage:
120 mg TID
60 mg TID [otc dosing]

MOA: lipase inhibitor

Therapeutic effect: fat excretion in stool

47
Q

Lorcaserin [Belviq]

A

Drug class: Schedule IV

Dosage: 10 mg BID

MOA: seratonin 2C receptor agonist

Therapeutic effect: appetite suppression

48
Q

Phentermine/Topiramate ER [Qsymia]

A

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

49
Q

Naltraxone ER/Bupropion ER [Contrave]

A

Drug class: none

Dosage: 16/180 mg BID

MOA:Opioid antagonist/anti- depressant

Therapeutic effect: Appetite regulation

50
Q

Liraglutideb [Victoza/Saxenda]

A

Drug class: none

Dosage: SQ 3mg daily

MOA: GLP-1 receptor agonist

Therapeutic effect: appetite suppression

51
Q

Cautions: Orlistat [Alli]

A

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

52
Q

Cautions: Lorcaserin [Belviq]

A

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

53
Q

Cautions: Phentermine/Topiramate ER [Qsymia]

A

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

54
Q

Cautions: Naltrexone ER/Bupropion ER Contrave

A

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

55
Q

Cautions: Liraglutide [high dose] Victoza/Saxenda

A 
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
56
Q

Metabolic syndrome

A

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.

Advanced Pharmacology (18 decks)

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