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233 2nd midterm > Other Endocrine Disorders & Prostate Cancer > Flashcards

Other Endocrine Disorders & Prostate Cancer Flashcards

1
Q

Hypothalamus often secretes a __________ that
acts on the hypothalamus to modify hormone
secretion

A

releasing factor

ex:
– Thyrotropin release factor
– Gonadotropin releasing factor

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2
Q

Hormone release regulates its secretion via

negative feedback mechanisms on?

A

– Hypothalamus

– Anterior pituitary

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3
Q

Growth Hormone

describe its secretion
what hormone regulates its secretion

A

Growth hormone (GH) is the most abundant ant pituitary hormone (recombinant GH = somatropin)
– Secretion rates high in newborns and decrease at ~4 years of age and maintained till puberty, followed by further declines
– Secretion regulated by GHRF
- increases during deep sleep for children 10-100x
- doping not easily detected with high flucuations

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4
Q

Growth Hormone

Clinical use? (3)

AE? (2)

A

– To treat individuals with pituitary dwarfism (GH deficiency)
– To promote growth and correct short stature in women with Turner’s Syndrome (one X chromosome missing or altered)
– Used illicitly by athletes to increase muscle mass (e.g. Barry Bonds)

  • similar to acromegaly: hypertension, carpal tunnel syndrome*, diabetes
  • cardiomegaly*: enlarged heart
  • cardiomyopathy: dysfunc in absence of atherosclerosis
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5
Q

Growth Hormone

what kind of receptor?
what does it stimulate?

A

GH receptor is a class I cytokine receptor
– GH and its analogues stimulate growth
– Stimulates hepatic production of insulin-like growth factor (IGF)
– IGF promotes uptake of amino acids and protein synthesis in skeletal muscle & cartilage of long bones
– Mecasermin can also be used (recombinant IGF-1)

Back then - get from cadavers - degenrative diseases
Now with recombinant technology, bacterial culture
Humans only respond to human GH

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6
Q

Growth Hormone

IGF Receptor Signaling
activates? (2)

A

IGF-1 binding to the IGF-1 receptors stimulates cell growth through 2 pathways involving initial activation/binding of insulin receptor substrate (IRS) proteins
– Activation of Ras: mitogen-activated protein kinase (MAPK) turns on DNA required for cell prolif
– Activation of Akt
▪ Leads to activation of mTOR (potent stimulator of protein synthesis)
- cell survival, cell growth, cell cycle

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7
Q

Growth Hormone Receptor Antagonists

what is acromegaly?
what is a GH receptor antagonist?

A

Acromegaly
– A disorder characterized via excess growth hormone secretion in adults (surgical removal is an option)

• Pegvisomant
– Modified analogue of GH that prevents actions of GH on liver receptors to stimulate IGF secretion

• Pharmacokinetics
– Subcutaneous injection (protein)
– Addition of polyethylene glycol increases half-life to ~2 days

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8
Q

Growth Hormone Receptor Antagonists

AE?

A

– Elevated liver enzymes (contraindicated in people with severe liver disease)

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9
Q

Other Treatments for Acromegaly

Somatostatin Analogues
Name 3

A

Somatostatin inhibits secretion of ant pit growth hormone (and many others)

– Octreotide - primary use for excess GH
– Lanreotide - used for thyroid
– Pasireotide - excess glucocorticoid secretion

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10
Q

Other Treatments for Acromegaly

Somatostatin Analogues

MOA?

A

– Mimic actions of somatostatin (octreotide signals through somatostatin receptor 2/5)
- act on ant pit to prevent GH release
– Inhibit GH secretion

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11
Q

Other Treatments for Acromegaly

Somatostatin Analogues

AE?
contraindication?

A

– Cardiovascular (*sinus bradycardia)
– GI (abdominal pain, diarrhea, nausea)
– CNS (headache, fatigue)
- pain at injection site

• Contraindicated/Use Caution
– Type 1 diabetes
▪ Hypoglycemia
Somatostatin can cause hypoglycemia or hyperglycemia
Decreases insulin from beta and glucagon from alpha cell
-Depends on balance of insulin and glucagon secretion

• Surgery/Radiation therapy arepreferred treatment options (most effective in small tumors)

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12
Q

Hormone Replacement Therapy

how does it work?
what are the benefits?

A

For post-menopause
– Cyclic or continuous administration of low dose estrogen with or without a progestogen (not treatmnet of choice)

Benefits:
– Prevent menopausal symptoms (e.g. hot flashes, chills, night
sweats, vaginal dryness, mood changes, etc.)
– Protect against osteoporosis
– Does not reduce the risk of coronary heart disease
- CV risk increases after post-menopause but not due to lack of estrogen

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13
Q

Hormone Replacement Therapy

AE? (2)

A

– Cyclical withdrawal bleeding
– *Increased risk of endometrial cancer (w/o progestogen)
– *Increase risk for breast cancer (related to duration of use)
– Increased risk of thromboembolism, greater than 5 year use

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14
Q

Testosterone

functions? pharmacology?

A

– Maturation of reproductive organs and development of secondary sexual characteristics
– Maintenance of spermatogenesis & maturation of spermatozoa
- LH = ICSH (interstitial cell stim hormone)
- Sertoli cells and interstitial to increase secretion of testosterone

– Testosterone acts via nuclear receptor signaling (androgen receptor (AR))
– Dihydrotestosterone - binds androgen receptor - dimerizes, nuclear receptor

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15
Q

Testosterone HRT

what can it treat?

A

– Male hypogonadism due to pituitary or testicular disease
– Female hyposexuality following ovariectomy

Free hormone is the active one that mediates effects
negative feedback mechanism

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16
Q

Testosterone HRT

AE? (3)

A 
– *Infertility with continued use (decreased gonadotropin release)
– *Salt & water retention (edema)
– *Acne
– Impaired growth (children)
– Masculinization in women
17
Q

Prostate cancer

what happens with estrogen and testosterone?

A

• Tumors in hormone sensitive tissues (e.g. prostate
gland, breast) may be hormone dependent
• Growth of these tumors can be inhibited by;
- Hormone agonists/antagonists
- Agents that inhibit hormone synthesis

Malignant cells express repceptors of estrogen or testosterone - excess stimulates growth of tumor
- manipulate hor,ones to treat prostate cancer

18
Q

Prostate cancer

Gonadotropin Releasing Hormone Analogues (5)

A 
– Gonadorelin (synthetic GnRH)
– Buserelin
– Leuprorelin
– Goserelin
– Nafarelin
19
Q

Prostate cancer

Gonadotropin Releasing Hormone Analogues (5)
MOA?

A

– Chronic administration inhibits the release of gonadotropins (FSH & LH)
– Leads to suppression of testicular steroidogenesis due to decreased levels of LH and FSH, and subsequent decrease in testosterone

GnRH - pulsatile can increase FSH or LH and increase testosterone
Given chronically, will decrease secretions

20
Q

Prostate cancer

Gonadotropin Releasing Hormone Analogues (5)
AE? (2)

A

– *Transient surge of testosterone secretion: intial actions elevate LH and FSH, need to use with anti-androgen in the first few months
– *Decreased libido
– Hot flash/flush

21
Q

Prostate cancer

GnRH receptor antagonist

name?
MOA?

A

Degarelix
– Reversibly binds to GnRH receptors in anterior pituitary to block receptor, decreasing FSH and LH secretion
– Results in rapid androgen deprivation and decrease in testosterone levels
avoids transient surge

22
Q

Prostate cancer

GnRH receptor antagonist - Dagarelix
AE?

A

– Hot flash/flush

23
Q

Prostate cancer

Non-Steroidal Anti-Androgens (5)

A

– Bicalutamide
– Enzalutamide
– Tlutamide
– Nilutamide
– Cyproterone: steroidal - deriverate of progesterone
Low activity, can compete with testosterone receptors and prevent action

24
Q

Prostate cancer

Non-Steroidal Anti-Androgens (5)

MOA?

A

– Inhibit androgen actions by competing with androgens for binding to androgen receptors in target tissue
– Can also be used to control testosterone surge (“flares”) caused by GnRH analogues

25
Q

Prostate cancer

Androgen Biosynthesis Inhibitors
name 1
MOA?

A

Abiraterone

– Selectively inhibits CYP17 (an enzyme expressed in and required for androgen biosynthesis in testicular, adrenal and prostatic tumor tissues
- prevent synthesis of testosterone

26
Q

Prostate cancer
Androgen Biosynthesis Inhibitors

AE (1)

A

– Hypertension
– Hypokalemia
– *Peripheral Edema: CYP17 also metabolizes neurocorticoids
- Now we are preventing their breakdown which leads to water rentention and can lead to edema

27
Q

Alopecia (Hair Loss)

cause?

what is an inhibitor of 5α-reductase

A

Androgens
– Stimulate hair growth on face, chest, back
– Inhibit hair growth on scalp

Finasteride
– Inhibitor of 5α-reductase (prevents conversion of
testosterone into the more potent dihydrotestosterone)
(most potent forma nd affinity for receptor)
– Applied topically and can take months to produce effects

takes a long time to see effects

28
Q

Alopecia (Hair Loss)

finasteride adverse effects? (1)

A
  • *reduced libido (impotence)

- tenderness of the breasts

29
Q

Alopecia (Hair Loss)

another drug for hair loss?

A

Minoxidil - better for alopecia
▪ Vasodilator originally developed for hypertension
▪ In hair follicles is converted to the more potent
metabolite, minoxidil sulfate
▪ Minoxidil sulfate increases blood supply to hair
follicles, thereby stimulating growth of new hair

  • Hair follicle is often resting and not in state to grow more
  • Need to shed hair first
  • Often initially, there will be noticeable hair loss before growth
30
Q

describe hirsutism

what can be used to treat it?

A

Excessive body hair in men and women on parts of
the body where hair is normally absent

Eflornithine - gets rid of hair growth on face
▪ Originally developed as an antiprotozoal agent
▪ Irreversibly inhibits ornithine decarboxylase in hair
follicles to reduce cell replication and the growth of new hair follicles
- Required for formation of polyamines - stabilize DNA during replication
▪ May cause acne

31
Q

what can prevent menopausal symptoms or osteoporosis?

A

Low-dose estrogen or estrogen/progestogen
combinations are used as hormonal replacement
therapy

32
Q

which drugs antagonize actions of GH to treat acromegaly

A

Pegvisomant (modified GH analogues) or somatostatin analogues (octreotide)

33
Q

what can be used for male hypogonadism

or female hyposexuality following ovariectomy?

A

Hormone replacement therapy with testosterone

34
Q

Prostate cancer can be treated with the following (3)

A

– GnRH analogues (inhibit FSH/LH secretion with chronic use)
– Non-steroidal anti-androgens
– Abiraterone

35
Q

Alopecia is treated with the following (3)

A

– Finasteride
– Eflornithine
– Minoxidil

233 2nd midterm (13 decks)

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