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Pharm 1 - SP19 > 34 - endocrine 2 > Flashcards

34 - endocrine 2 Flashcards

1
Q

chemical composition of bone

67% _
33%_

A

67% inorganic HA

33% organic (28%collagen) 5%noncollagenous proteins

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2
Q

bone generating cells

A

osteoblasts

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3
Q

mature bone cells, spider shaped and maintain bone tissue

A

osteocytes

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4
Q

bone destroying cells

A

osteoclasts

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5
Q

Bone formation is the process by which osteoblast cells
synthesize bone. In the process of bone formation,
osteoblasts function in groups of connected cells.
Individual cells cannot make bone, and the group of
organized osteoblasts together with the bone made by
a unit of cells is usually called the _

A

osteon

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6
Q

Bone resorption is the process by which
osteoclasts break down bone and release the
minerals, resulting in a transfer of _ from
bone fluid to the blood.

A

calcium

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7
Q

If the body is low on Ca++, _ will be released and these 3 things happen

1) bone
resorption will increase, 
2) Ca++ elimination by the kidney will decrease, 
 3) Ca++
absorption by the gut will increase
A

Parathyroid hormone (PTH)

3 - indirect effect - due to vitamin D kidney Enhance vitamin D production (calcitriol) - enhances absorption of Ca from gut

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8
Q

Release of Parathyroid Hormone (PTH)

high/low levels of:
Ca
PO4
vitamin D

A

Ca++ sensor is a G protein
coupled receptor

High Ca++ diminishes PTH release
low Ca stimulates PTH release

High PO4
3- increases PTH
release by binding Ca+

Vitamin D diminishes PTH release through
changes in gene expression (feedback effect)

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9
Q

when PTH is released what happens to blood levels of

Ca
PO4

A

Ca increases

PO4 decreases (because Ca increases)

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10
Q

PTH

t½ in plasma, _ minutes

Acts on two receptors

PTHR1: _ and _

PTHR2: CNS, pancreas, testis, placenta

A

only 4 min 1/2life

bone and kidney

PTHR1, sometimes Gαs, sometimes Gαq

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11
Q

PTH

Activation of PTHR1 receptors on osteoblasts, induces
expression of _, This leads to binding and
activation of osteoclasts and bone resorption

what does osteoprotegerin do?

A

RANK ligand (RANKL)

Important in the context of osteoporosis pharmacology

osteoprotegerin - inhibs this from happening - will bid to rankl and block osteoclast binding

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12
Q

PTH effects on the kidney

Maximize _ resorption, decrease _
3- resorption

Enhance vitamin _ production

A

Maximize Ca++ resorption, decrease PO4
3- resorption

Enhance vitamin D production (calcitriol) - enhances absorption of Ca from gut

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13
Q

Calcitriol plays a complex role in Ca++ homeostasis

but overall it causes _

A

increased Ca absorption from the gut

(decrease kidney excretion of Ca, increase bone resorption and mineralization, increase osteoclast development, decreases PTH secretion )

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14
Q

_ is released by parafollicular cells of the
thyroid in response to high serum Ca++. It
counteracts the effects of PTH.

A

Calcitonin

Increases bone formation
Decreases kidney resorption of Ca++.
Decreases Ca++ absorption by the gut

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15
Q 
Dental
Abnormalities due
to PTH issues can
also be an
indication of _
malfunction.
A

kidney

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16
Q

Treatment of hypoparathyroidism

Oral _ tablets

Vitamin _

Parathyroid hormone analogues (see osteoporosis)

A

Oral calcium carbonate tablets

Vitamin D

Parathyroid hormone analogues (see osteoporosis)

17
Q

Treatment of hyperparathyroidism

The calcimimetic cinacalcet: an allosteric activator of the calcium sensor. The
drug tricks the parathyroid glands into releasing _

Hormone replacement therapy (i.e. for postmenopausal women)

Osteoporosis drugs (next)

A

less parathyroid hormone.

18
Q

_ is a disease where increased bone weakness
increases the risk of a broken bone. It is the most common
reason for a broken bone among the elderly. Osteoporosis may
be due to lower-than-normal maximum bone mass and greaterthan-normal bone loss

A

Osteoporosis

Menopause or ovariectomy, (due to lower levels of estrogen),
alcoholism, anorexia, hyperthyroidism, kidney disease

Medications: antiseizure medications, chemotherapy, proton
pump inhibitors, selective serotonin reuptake inhibitors, and
corticosteroid

Smoking and sedentary lifestyle

19
Q

Drugs to treat osteoporosis

_ drugs that prevent the loss of bone
mass, used to treat osteoporosis
and similar diseases. They are the
most commonly prescribed drugs
used to treat osteoporosis
A

Bisphosphonates

Inhibit bone resorption and osteoclast activity

Restore bone density

Mechanism not totally understood

20
Q

Drugs to treat osteoporosis

Denosumab (trade names Prolia and Xgeva) is a _ that binds and inhibits RANKL.
Denosumab is contraindicated in people with low blood
calcium levels

A

human
monoclonal antibody

administered by a health care professional (60 mg subcutaneously every
6 months).

21
Q

Drugs to treat osteoporosis

_ bind estrogen receptors and act as agonists to enhance
estrogen activity in some tissues and act as antagonists to inhibit
estrogen activity in other tissues

A

Estrogen and SERMS (selective estrogen receptor
modulators

Hormones, such as estrogen, and SERMS can play a
role in osteoporosis prevention and treatment. However, there has
been some concern about potential side effects tied to the use of
hormone therapy. Some recommendations suggest using the lowest
dose of hormones for the shortest period of time

22
Q

Drugs to treat osteoporosis

Teriparatide is a recombinant protein form of _ hormone consisting of the
first (N-terminus) 34 amino acids, which is the bioactive portion of the hormone

A

parathyroid hormone

Endogenous PTH is the primary regulator of calcium and phosphate metabolism in
bone and kidney. PTH increases serum calcium, partially accomplishing this by
increasing bone resorption. Thus, chronically elevated PTH will deplete bone
stores.
However, intermittent exposure to PTH will activate osteoblasts more than
osteoclasts.
Thus, once-daily injections of teriparatide have a net effect of
stimulating new bone formation leading to increased bone mineral density.
Teriparatide is the first FDA approved agent for the treatment of osteoporosis that
stimulates new bone formation

23
Q

_ the
principal plasma
androgen

A

Testosterone

95% of testosterone comes
from Leydig cells of the testes
(other 5% from adrenal gland).
Some made in the ovary

24
Q

Testosterone synthesis and

release stimulated by _

A

LH

25
Q

The three
major
natural
estrogens

A

Estradiol (E2) - main secretory product of ovary

Made in liver
from estradiol
Estrone (E1)
Estriol (E3)

26
Q

Estrogen Receptors and Treatment of Breast Cancer

If the breast cancer
cells are estrogen
receptor positive,
estrogen is likely to
be driving cell
proliferation. The
drug tamoxifen
antagonizes the
effect of estrogens in
breast cancer cells
and blocks _
A

cell
proliferation

Binding of agonist(e.g.
estradiol to estrogen
receptor) produces a
conformational change
that exposes the AF-2
region of the receptor
Co-activator proteins
such as SRC-1 can only
bind to the receptor if AF2 is exposed. Thus, the
co-activators only bind to
the receptor if agonist is
bound.

Antagonists bind perfectly well to the receptor but their binding does not lead to
exposure of AT-2. Therefore, the antagonist receptor binds to the DNA, but does not
bind co-activators and the antagonist does not activate transcription.

27
Q

It is speculated that things like availability of _

determines whether the SERM acts as an agonist or antagonist.

A

co-activators

28
Q

Progestins

synthesized in

precursor to:

biological role in

males have progesterone receptors too. Not
tremendously well understood effects on male sexuality

A

synthesized in - corpus luteum
placenta
adrenal cortex

precursor to - androgens
estrogens
adrenocortical
hormones

bio role in menstrual cycle and
pregnancy

29
Q

_ and _ Hormones during the Menstrual Cycle

these fluctuate at specific times

A

Pituitary and Ovarian hormones

Coordinated pattern of FSH and LH secretion during
menstrual cycle required for follicle development,
ovulation and pregnancy

30
Q

Oral Contraceptives

estrogen +
progesterone

they block Block _
from the pituitary

progesterone
alone?

A

LH and FSH release

progesterone
alone - Thickening of cervical mucus (blocks
sperm from contacting egg), Block release of eggs from the ovary

31
Q

Emergency Oral Contraceptive Pills

Higher doses of progesterone alone, or progesterone plus
estrogen

RU486, (mifepristone) a low efficacy _ partial
agonist
also a glucocorticoid antagonist
Lower dose: emergency oral contraceptive
Higher dose: abortifacient (first several months)

A

progesterone partial agonist

Pharm 1 - SP19 (26 decks)

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