Calcium

Front 1

Causes of hypocalcemia (3)

Back 1

1.) decreased vitamin D activation (no UV, high enzyme metabolism)
2.) decreased calcium absorption/intake (intestinal disease)
3.) secondary to disease (hypothyroidism)

Front 2

Causes of hypercalcemia (3)

Back 2

1.) malignancy, osteolysis, hyperthyroidism
2.) too much vitamin D intake (summer)
3.) atrophy/disuse due to immobilization

Front 3

Treatment
a.) hypocalcemia
b.) hypercalcemia

Back 3

a.) hypocalcemia: hormone replacement that increases Vit D or PTH; calcium supplements
b.) hypercalcemia: calcimimetics that suppress PTH secretion

Front 4

Osteoclast vs osteoblast & role in osteoporosis

Back 4

Osteoclast clashes down bown. Osteoblast builds back up bone. In osteoporosis, there are more osteoclasts than osteoblasts, leading to brittle bones

Front 5

Primary osteoporosis: define

Back 5

Actual skeletal disease where the bone density is decreased and there is bone tissue deterioration

Front 6

Secondary osteoporosis

Back 6

Due to diseases like hyper(para)thyroid, low Vit D/low estrogen, drug induced glucocorticoids/ anticonvulsant, renal disease, etc.

Front 7

5 drugs you wouldn't expect to cause bone loss

Back 7

1.) thiazolidinediones
2.) SSRIs
3.) anti-epileptics
4.) cancer treatment
5.) GERD treatment (PPIs, H2 antagonists)

Front 8

Calcitonin
a.) what is required for activity?
b.) enzymes involved

Back 8

a.) disulfide bond is essential for calcitonin activity
b.) aminopeptidase involved, carboxypeptidase cannot cleave carboxy end because replaced with an amide

Front 9

Calcitonin
a.) location
b.) what affects its secretion?
c.) main MOA (3)

Back 9

a.) thyroid gland, parathyroid gland, thymus gland
b.) high serum calcium stimulates calcitonin secretion. calcitonin works to tone down serum calcium
c.) decrease calcium mobilization from bone (inhibits osteolysis from osteoclast, which decreases bone resorption; decreases vitamin D activation which decreases intestinal calcium absorption, increases calcium renal elmination

Front 10

Parathyroid hormone
a.) how to make it active?
b.) what affects its secretion?
c.) main MOA (3)

Back 10

a.) cleave twice because it is a pre-pro-hormone. serine is the first aa.
b.) low serum calcium increases the secretion of PTH. PTH works to increase calcium
c.) increases calcium mobilization out of bone (by increases adenylate cyclase, which increases cAMP, which increases osteoclast activity and bone resorption); activates vitamin D to increases intestinal absorption of calcium, increases renal tubular reabsorption of calcium

Front 11

Vitamin D
a.) synthesis location
b.) activation location
c.) effect on calcium

Back 11

a.) made in the skin
b.) activated in liver and kidney
c.) increases calcium absorption only in the activated form!

Front 12

Vitamin D
a.) liver effect
b.) kidney effect
c.) enzyme and cofactors needed

Back 12

a.) causes 25-OH hydroxylation
b.) causes 1-OH hydroxylation
c.) Vitamin D 25 hydroxylase (liver), Vitamin D 1 hydroxylase (kidney) and O2/NADPH

Front 13

Patient has liver disease. What vit D to give?

Back 13

Give a 25-OH compound

Front 14

Patient has kidney disease. What vit D to give?

Back 14

Give 1-OH compound

Front 15

24 hydroxylase

Back 15

An enzyme that is activated when there is a high amount of calcium or calcitriol. It makes a 24-hydroxy metabolite that makes it less active and increases secretion

Front 16

Activated vitamin D MOA (3)

Back 16

Vitamin D works to increase calcium. Thus:
1.) increase intestinal absorption of dietary calcium to increase serum calcium
2.) decrease renal excretion of calcium = increased serum calcium
3.) increases calcium release from bone = increased serum calcium

Front 17

Vitamin supplements that don't require any activation? (2)

Back 17

Calcitriol and paricalcitol. Good for dialysis patients

Front 18

Vitamin supplements that need 2-step activation? (2)

Back 18

Cholecalciferol (D3) and ergocalciferol (D2). Need liver (25 hydroxylation) and kidney (1 hydroxylation) for it to become active

Front 19

Partially activated vitamin D (2)

Back 19

The two D's: Doxycalciefrol and DHT dihydroxytachysterol need the liver for 25 hydroxylation

Front 20

Premarin
a.) name of therapy
b.) indication
c.) MOA/classification of therapy
d.) main components

Back 20

Premarin
a.) estrogen replacement therapy
b.) for the prevention and treatment of osteoporosis in post-menopausal women BEFORE there is significant bone loss
c.) inhibition of osteoclast activity = anti-resorptive therapy
d.) conjugated estrogen (anti-resorptive); progesterone (decrease cancer risk and uterine stimulation)

Front 21

SERM
a.) abbreviation
b.) drugs (2)
c.) indication
d.) MOA/classification of therapy

Back 21

a.) SERM = selective estrogen receptor modulator
b.) tamoxifen, raloxifene
c.) osteoporosis treatment
d.) estrogen receptor agonist at skeletal muscle (anti-resorptive/ decrease osteoclast activity) and cardio. estrogen antagonist at breast and endometrial tissue

Front 22

Bisphosphonates
a.) MOA
b.) SAR (3)

Back 22

a.) anti-resorptive; decreases osteoclast activity/ decreases bone resorption. Also increases calcium deposit into bone.
b.) geminal bisphosphonate (targets drug to bone), OH group (increases antiresorptive potency by maximizing affinity of drug to bone matrix, amine containing side-chain increases antisorptive potency

Front 23

Calcitonin salmon
a.) indication
b.) MOA/classification
c.) type of therapy
d.) ADR

Back 23

a.) osteoporosis treatment
b.) decreases osteoclast activity via decreasing lifespan and number (anti-resorptive) and increases bone density (increases mineralization within 6 months)
c.) hormone therapy but non-estrogenic
d.) increases PTH, which neutralizes its effect in the long term

Front 24

Which osteoporosis drug also treats bone pain?

Back 24

Calcitonin salmon

Front 25

Which drug both decreases osteoclast activity and increases bone mineral density?

Back 25

calcitonin salmon

Front 26

Teriparatide
a.) indication
b.) MOA/classification
c.) black box warning
d.) c/i (2)

Back 26

a.) osteoporosis
b.) mimics PTH. Supposed to give it intermittently/ not continuously so that it will increase osteoblast activity. Thus it is a bone-forming/ bone restorative drug (the only one)
c.) osteosarcoma
d.) growing kids/adults, Paget's disease

Front 27

Difference between calcitonin and PTH

Back 27

a.) calcitonin works to decreases calcium in the blood (decrease resorption)
b.) PTH works to increase calcium in the bood (increase resorption)

Front 28

Denosumab
a.) indication
b.) MOA/classification

Back 28

a.) osteoporosis, cancer patients who are experiencing bone loss
b.) denosumab is a monoclonal antibody. It mimics the activity of osteoprotegerin and binds to RANKL, which inhibits osteoclast activity. Antiresorptive.

Front 29

RANKL
a.) what
b.) drug against it

Back 29

a.) receptor that activates osteoclast activity. RANKL activity is high in osteoporosis patients. This large imbalance causes bone loss
b.) denosumab

Front 30

Osteoprotegerin
a.) what
b.) drug mimic

Back 30

a.) a product produced by osteoblasts that bind to RANKL and prevent osteoclast activation
b.) denosumab

Front 31

Sodium fluoride
a.) MOA
b.) problem

Back 31

a.) increase osteoblast activity for osteoporosis treatment
b.) divets are not sturdy. same number of fractures

Front 32

Bone-forming therapy for osteoporosis (4)

Back 32

1.) Teriparatide
2.) Recombinant human PTH
3.) sodium fluoride
4.) strontium ranelate

Front 33

Antiresorptive therapy (2)

Back 33

1.) calcitonin
2.) denosumab