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Therapeutics 2 Kappa Epsilon > Hockerman Ca2+ Homeostasis > Flashcards

Hockerman Ca2+ Homeostasis Flashcards

1
Q

what kind of cells PUT Ca2+ into bones?

A

osteoBLASTS (building bone)

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2
Q

what do osteocytes do?

A

are inside bone to control the osteoblasts and osteoclasts

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3
Q

what cells release PO4 and Ca2+ from bone?

A

osteoclasts

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4
Q

Bone is _____ sensitive: _______ force is detected by cell processes that extend into canaliculi which forms a network involving _______ and ______

A

load; mechanical; ACTIN; Connexin 43

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5
Q

Parathyroid Hormone:

  • is a ________ hormone secreted from parathyroid gland
  • it is ____ amino acids long; cleaved from a precursor that is _____ amino acids long;
  • what part of the hormone has full activity?
  • if ______ is deleted from the hormone - activity is lost
A

peptide; 84; 115; amino acids 1 - 34; amino acid 1 & 2

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6
Q

The parathyroid’s hormone is in charge of maintain what?

A

keeping a constant Ca2+ concentration in extracellular serum

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7
Q

what actions does PTH do?

  • increase Ca2+ reabsorption from ______
  • increase Ca2+ resorption from ______
  • increased _____ lost in urine
  • increased ______ produced by kidney
A

collecting tubules; bone; PO4-; Vit. D

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8
Q

what is the first step of Vitamin D Synthesis

A

7 dehydrocholesterol –> Vitamin D3 (Cholecalciferol) via UV light

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9
Q

Liver’s Role in Vitamin D synthesis - ?

A

Vitamin D3 –> 25 hydroxyvitamin D3 via Vit D 25- hydroxylase

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10
Q

Kidney’s Role in Vitamin D Synthesis - ?

A

hydroxylase enzyme (1a or 24) to make 1,25 Vit. D3 or 24,25 Vit. D3

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11
Q

What are the actions of Vit. D

  • increased _________ absorption from small intestine
  • increases reabsorption of _______
  • feedback inhibition of ______
  • will have indirect (slow or fast) effects on cells
A

ca2+/PO4; Ca2+/PO4; PTH; slow

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12
Q

How does Vit. D help with absorption of Ca2+ from intestines

A

it up regulates TrpV6, Calbindin-D9k; Ca2+ATPase - all of those help Ca2+ go from lumen to the blood

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13
Q

Role of TrpV6 in absorbing Ca2+ from the intestine

A

Ca2+ channel

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14
Q

Role of Calbindin-D9k in absorbing Ca2+ from the intestine

A

it is the calcium “chaperone” guides Calcium across the cell

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15
Q

Role of Ca2+ATPase in absorbing Ca2+ from the intestine

A

pushes Ca2+ out into the plasma from the cell

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16
Q

_______ is released from the thyroid gland and is a negative regulator of serum Ca2+

A

Calcitonin

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17
Q

How does calcitonin act as a negative regulator of serum Ca2+

A
  • inhibits osteoclastic bone resorption

- increases Ca2+ and PO4 loss in urine (aka less is absorbed)

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18
Q

Calcitonin is triggered to be release by what?

A

high levels of Ca2+

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19
Q

Explain Paget’s Disease

A
  • UNCONTROLLED OSTEOCLASTIC BONE RESOPRTION AND SECONDARY BONE FORMATION (bone pain/deformities, loss of hearing and hypercalcemia)
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20
Q

Paget’s Disease patients are at risk of having (hypo or hyper) calcemia

A

Hyper - because hella osteoclastic bone resorption is occurring

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21
Q

Risk Factors for Osteoporosis

A

Physical inactivity (try weight lifting); age; low Ca2+ intake in early years; long term glucocorticoid

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22
Q

Possible causes for Hypercalcemia

A
  • hyperparathyroidism

- malignant tumors

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23
Q

Hypercalcemia can cause what ?

A

CNS symptoms (depression, coma)

24
Q

Hypocalcemia can be caused by what?

A
  • Hypoparathyroidism

- vit. D deficiencies

25
Q

Hypocalcemia can cause what?

A
  • neuromuscular distrubances
  • paresthesias, tetany,
    muscle cramps
26
Q

Different Preparations of Vit. D that are available

A
  • Vit D.3 ( OTC - doesn’t have that 1 or 25 OH) - therefore needs kidney AND liver function
  • 25OH Vit. D3 - NEEDS KIDNEY FUNCTION
  • 1,25 OH Vit. D3 - does not need function of kidney or liver
27
Q

Clinical uses for Vit. D

A
  • hypocalemia
  • hypoparathyroidism (used as supplement bc usually PTH stimulates Vit. D to be made)
  • hyperparathyroidism (secondary to CKD - used as feedback inhibition to have PTH chill)
28
Q

Bisphosphonates: inhibit bone ______

A

resorption

29
Q

Bisphosphonates: MOA - 2 ideas/options
- reduce ________ and ________ of hydroxyapatitie crystals
OR
- disrupt _______, induce _______ and inhibit FPP synthesis in _________

A

formation; dissolution; cytoskeleton; apoptosis; osteoclasts

30
Q

Bisphosphonates: Counseling tips

A
  • taken w/ H20
  • take 30 min before breakfast (because drug interactions..?)
  • gastric irritation (therefore sit up after taking it)
  • may cause Hypocalcemia
31
Q

List all the bisphosphonates

A
  • alendronate
  • risendronate
  • ibandronate
  • zoledronate
  • eitdronate
  • tiludronate
  • pamidronate
32
Q

What bisphosphonates are approved for Paget’s and cancer (NOT osteoporosis)

A
  • pamidronate
  • tiludronate
  • etidronate
33
Q

what bisphosphonates ARE approved osteoporosis

A
  • alendronate
  • risedronate
  • ibandronate
  • zoledronate
34
Q

MOA of Bisphosphonates:

  • ________ of farnesyl pyrophosphate synthase
  • disrupts prenylation of proteins in _________
  • affects isoprenoid activity and ______ can induced
A

inhibition; osteoclasts; apoptosis

35
Q

Second line treatment for Osteoporosis

A

Estrogens and SERMs

36
Q

Calcitonin will _______ osteoclast activity and thats why it can be used for ________

A

osteoporosis (only as alternative for ERT)

37
Q

side effects of Calcitonin (given as Calcimar or Miacalcin)

A

urticaria; hand swelling, nausea

38
Q

Clinical Uses of Calcitonin (given as Calcimar or Miacalcin)

A
  • pagets disease
  • hypercalcemia (secondary to malignancy)
  • Alt. therapy for osteoporosis (alt. to ERT)
39
Q

what kind of drug is Forteo?

A

its the first 34 amino acids of PTH

40
Q

forteo = ? (generic)

A

Teriparatide

41
Q

usually don’t want parathyroid because stimulates resorption of bones BUT forteo can be used to help with osteoporosis - HOW?

A
  • given periodically - and Ca2+ and Vit. D are supplemented

- this will preferentially stimulate osteoblasts NOT osteoclasts

42
Q

List the components for differentiating osteoclasts

A
  • RANKL
  • RANK
  • OPG (osteoprotegerin)
43
Q

Describe how osteoclasts are differentiated

A
  • RANKL (a ligand on an osteoblast) will bind to RANK (a receptor on an osteoclast precursor) - will create an osteoclast
  • RANKL can bind to OPG which prevents osteoclast differntiation
44
Q

Continuous PTH - will lead to….

_____ RANKL and _____ OPG

A

MORE RANKL and LESS OPG (that means more osteoclast differentiating!

45
Q

Risk of _______ with Tymlos (abaloparatide) - a PTH related peptide

A

osteocarcinoma

46
Q

________ drug is a humanized monoclonal Ab against RANKL - aka will prevent osteoclast precursos from differentiating into osteoclasts

A

Prolia (Denosumab)

47
Q

New strategy for Osteoporosis: - drug involving serotonin….

A

serotonin INHIBITS osteoblast proliferation TPH1 helps serotonin in the gut be made - therefore inhibit TPH1 to decrease serotonin and therefore serotonin too

48
Q

New strategy for Osteoporosis: - drug involving cathepsin K

A

cathespin K - is released by osteoclasts and will degrade type 1 collagen in bone = therefore use a cathepsin K inhibitor

49
Q

Normal Ca2+ plasma level (only Free Ca2+)

A

1.1 - 1.3 mM

50
Q

Drug classes listed that affect Ca2+ levels

A
  • loop diuretics (increased Ca2+ excretion)
  • Thiazides (decreased excretion)
  • PPIs/H2 antagonists (decreased absorption)
  • Carbemazepine, isoniazid, theophylline, rifampin (induction of vit. D catabolites
51
Q

how do loop diuretics affect Ca2+

A

increase Ca2+ excretion

52
Q

how do thiazides affect Ca2+

A

decrease Ca2+ excretion

53
Q

how do PPIs and H2 antagonists affect Ca2+

A

decrease absorption

54
Q

Cinacalcet (Sensipar) is used to treat what?

A

Hyperparathyroidism

55
Q

Cinacalcet (Sensipar) binds to _______ on the ______ to inhibit the release of ______

A

CaR (calcium sensing receptor); PTH gland; inhibit PTH

56
Q

Cinacalcet (Sensipar) will decrease both ______ and _____ levels

A

Ca2+ and PTH

Therapeutics 2 Kappa Epsilon (22 decks)

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