2.5 Hormones and Stuff (part 2) - Shah

im dying

some estrogens are able to block ________ effects

a. estrogen

b. androgen

c. progesterone

d. dopamine

b

example of an estrogen that can block androgen effects

fofestrol

estrogens are used to recruit cells in _____ to enter _____so they are better targets for cytotoxic drugs

a. G0; G1

b. G1; G2

c. G0, S

d. G1; S

a

why does changing cells to G1 from G0 benefit cytotoxic drugs?

bc cytotoxic drugs target dividing cells not resting cells

progestogens are used in the treatment of which two cancers?

endometrial cancer

renal cancer/ tumors

estrogens are highly _____

mitogenic

what does mitogenic mean tho fr?

substances that induce or stimulate cells to begin division

estrogens stimulate ____ growth in target organs

rapid

what are the estrogen receptors?

alpha and beta

which of the following is FALSE

a. estrogens are highly mitogenic

b. estrogen stimulate rapid growth in target organs

c. estrogens have two receptor subtypes

d. estrogen alpha and beta receptors are equally distributed in the body

d

estrogen alpha and beta receptors are _________ distributed in the various target organs

differentlially

where are estrogen alpha receptors found in the body? (7)

1. Adrenal

2. Epididymis

3. Kidneys

4. Ovary

5. Pituitary

6. Testis

7. Uterus

mnemonic for estrogen alpha receptor distribution

A Evil King Ordered People To Urinate

where are the estrogen beta receptors found in the body? (6)

1. Bladder

2. Brain

3. Epididymis

4. Ovary

5. Prostate

6. Uterus

mnemonic for estrogen beta receptor distribution

Brilliant Biologists Examine Ovaries, Prostates, Uteri

which estrogen receptor subtype is found in Adrenal, Kidney, Pituitary, Testis?

alpha

which estrogen receptor subtype is found in Brain, Bladder, Prostate?

beta

which areas of the body have both estrogen alpha and beta receptors?

• Epididymis

• Ovary

• Uterus

which two organs are estrogen beta receptor negative?

(which means they would respond to estrogen alpha stimulation)

mammary

testis

when developing drugs that target estrogen receptors, scientists _______ estrogen receptors to determine their 3d structure.

crystallizedd

when developing drugs that target estrogen receptors, scientists crystallized estrogen receptors to…

determine 3d structure

what does 3d structure of the estrogen receptors tell us when designing drugs?

where the drug binds

the shape of the binding pocket

difference between alpha and beta receptors

what is a SERM

selective estrogen receptor modulators

SERMS have both ___ and _________ properties

estrogen-like

anti-estrogen

SERMs are able to preferentially interact with which estrogen receptor subtypes?

both alpha and beta

name 4 examples of SERMS that bind to estrogen alpha receptors

DES

4-OH-tamoxifen

17B-estradiol

ICI 164384

name 3 examples of SERMs that bind to beta receptors?

17-a-estradiol

clomifene

moxestrol

SERMs act as ________ in the breast

antagonist

SERMs act as ______ in the bone

agonist

tamoxifen class

SERM

raloxifene class

SERM

toremifene class

SERM

ICI 182,780 class

pure ER antagonist

ICI 182, 780 is used in the treatment of….

estrogen dependent cancer

raloxifene is a SERM in the ____ class

benzothiophene

raloxifene produces estrogen like effects on ____ and ______

bone and lipid metabolism

raloxifene acts as an ______ in the bones and on lipid metabolism

agonsit

raloxifene produces antagonizing effects on the ___ and _______

mammary tissue / breast

uterus

raloxifene works as a ________ on the breast tissue

antagonist

T or F:

the effectiveness of raloxifene in reducing the risk of breast cancer has not been established.

T

tamoxifen acts as an estrogen antagonist the _________

breast

tamoxifen acts as an estrogen ______ the breast

antagonist

tamoxifen acts as an estrogen agonist in the _______ and ______

bone and uterus

tamoxifen acts as an estrogen ____in the bone and uterus

agonist

tamoxifen effect on bones

increase BMD

tamoxifen MOA

bind to estrogen receptors on the membrane of target cells, thus limiting the effects of estrogen breast tissue

tamoxifen might have other anti-tumor activities that can effect…

oncogene expression and promote apoptosis

tamoxifen CNS ADE

depression , light headed, dizzy, HA

tamoxifen GI ADE

N and V

tamoxifen Hematological effects

hypercalcemia

tamoxifen GU ADE

vaginal bleeding and discharge

menstrual irregularites

tamoxifen dermatological ADE

hot flashes and skin rashes

Toremifene is a derivative of…

tamoxifen

Toremifene has a _____ favorable effect on lipid levels than tamoxifen

more

Toremifene has a more favorable effect on ____ than tamoxifen

lipid levels

Toremifene class

oral nonsteroidal antiestrogen

Toremifene uses

tx of metastatic breast cancer in post menopausal women

SERMs only work in ____cancer

ER+

(estrogen receptor positive)

SERMs are often used in breast cancers that have metastasized to the bone, if the pt experiences pain at the effected site, what does that mean?

its a good thing bc the drug is workin

SERMs can lead to ___ damage

eye

aromatase inhibitors are _____ dependent and SERMs are _____ dependent

NOT ER+

ER+

aromatase inhibitors reduce the amount of _______ in the body

estrogen

anastrazole class

aromatase inhibitors

exestane class

aromatase inhibitor

letrozole class

aromatase inhibitor

androgens and antiestrogen receptor drugs cause ____ effects in women

masculinizing

men and women who are on androgens may develop ___ with prolonged therapy

acne

hypercalcemia

liver dysfunction

men who take estrogen products can develop ____ or ____

feminine manifestations

gynecomastia

progestins are used to treat cancer of the ____, _____, or _____

breast, kidney, uterus

progestins work to change the cancer cell’s ability to…

react to other hormones and proteins that cause tumor growth

progestins can ____ the growth of a tumor

stop

Medroxyprogesterone admin

oral

Megestrol admin

oral

Norethindrone admin

oral

Progesterone admin

oral

Hydroxyprogesterone admin

parenteral

Medroxyprogesterone admin

parenteral

Progesterone admin

parenteral

Progesterone Gel Suppositories admin

vaginal

progestin containing drugs CI:

CV/ Clot risks (6)

hx of clots, stroke, varicose veins, heart disease, high cholesterol

progestin containing drugs CI:

neurologic disorders (3)

hx of migraines, epilepsy, CNS disorders

progestin containing drugs CI:

organ disfunction (4)

chronic liver dx, chronic kidney dx, DM, asthma

corticosteroids are used in conjunction with chemotherapy medications like ________ (name 3)

anthracylins

vincristine

methotrextate

some corticosteroids are used to treat…

adult leukemia

adult lymphoma

acute childhood leukemia

name the three most common corticosteroids that are used in cancer treatment

dexamethasone

hydrocortisone

methylprednisolone

corticosteroid MOA:

inhibit _____ (4 things)

lymphocyte proliferation

protein synthesis

genes that code for cytokines, IL, and TNF-y

expansion and antibody synthesis

corticosteroids MOA:

they are cytotoxic due to _______

inhibition of protein synthesis and induction of apoptosis

corticosteroids MOA:

they inhibit protein synthesis which leads to ____

apoptosis

corticosteroids MOA:

_____ cell mediated immunity

suppress

corticosteroids MOA:

they act by inhibiting genes that code for ______

cytokines, interleukin and TNF-γ

corticosteroids MOA:

inhibits cytokine production to reduce __________

T cell proliferation

corticosteroid SE:

metabolic effects

hyperglycemia

insulin resistance

why should the use of corticosteroids be cautioned in DM?

bc steroids increase glucose production!

(can lead to hyperglycemia and insulin resistance)

corticosteroid SE:

bone effects (4)

reduced bone density

osteoporosis

higher fracture risk

slower fracture repair

why do corticosteroids cause bone effects?

steroids weaken bones/ break them down

corticosteroids can lead to ______ due to increased visceral/truncal fat deposition and appetite stimulation

weight gain

corticosteroids can lead to weight gain due to …

increased visceral/truncal fat deposition and appetite stimulation

corticosteroid SE:

protein breakdown

muscle breakdown (proteolysis)

weakness

reduced muscle mass

increased urea formation

negative nitrogen balance

corticosteroids can cause _________ if stopped suddenly so must taper every time!!!

adrenal insufficiency

Cytadren (aminoglutethimide) MOA

inhibits the enzymatic conversion of cholesterol to D5-pregnenolone