Parathyroid Pharm

Question 1

Effect of loop diuretics

Answer 1

Dec plasma Ca++

Question 2

Effect of thiazide diuretics

Answer 2

inc plasma Ca++

Question 3

Use of thiazides

Answer 3

hypercalciuria ( to decrease urinary Ca)

Question 4

Use of loops

Answer 4

Hypercalcemia (dec plasma Ca)

Question 5

Actions of Vit D

Answer 5

• Decreased release of PTH
• Increased synthesis of Ca++-binding protein and channel
• Enhanced dietary absorption of Ca++ and PO4
• Induce RANK ligand in OBs: role in bone mineralization
• Decreased excretion of Ca++ and PO4

Question 6

Which agent is more preferred Vit D2 or D3?

Answer 6

D3 preferred over D2 (Less efficient in elevating 25-OHD levels than D3 in depletion states)

Question 7

Best vit D supp in liver disease?

Answer 7

Calcifediol (25(OH)D3)

Question 8

Best vit D supp in renal disease?

Answer 8

1,25(OH)2 D3 (calcitriol)

Question 9

Dihydrotachysterol

Answer 9

• Hepatic 25-OH activation (doesn’t require renal activation) - equivalent to 1-OHD3 in function
• Can be used in disorders that calcitriol is used

Question 10

Calcitriol Analogs

Answer 10

paracalcitol

Question 11

paracalcitol MOA and use

Answer 11

• Inhibit PTH release from gland
• used in secondary hyperparathyroidism
• Does NOT increase Ca++ absorption/mobilization from bone(NO hypercalcemia)

Question 12

Calcimimetics MOA

Answer 12

bind Ca++-sensing cells on PT gland

- Inc Ca++: reduced release of PTH (no hypercalcemia)

Question 13

Actions of Calcitonin

Answer 13

-Inhibits osteoclastic bone resorption
-Increases excretion of Ca++ and PO4
No clinical findings in deficiency (thyroidectomy) or excess (thyroid carcinoma)

Question 14

Actions of Estrogen on Bone

Answer 14

• Positive effects on bone mass
• decrease number and activity of OCs
• Estrogens increase OB production of osteoprotegerin (OPG, decoy RANKL receptor)

Question 15

Glucocorticoid Actions on Bone (pharm doses)

Answer 15

Glucocorticoids decrease bone density:

• Lowering of serum Ca++ (antagonize Vit D effect on gut)
• increase in PTH then stimulates osteoclast activity
• Increase production of RANK-L by OBs and decrease OPG: inc OC activation & increase bone resorption
• Risk of osteoporosis when GCs used for inflammation
• Plus suppressive effects on osteoblasts

Question 16

Medications causing low bone mass

Answer 16

Glucocorticoids,
Excess Thyroid Hormone,
Anticonvulsants

Question 17

Osteoporosis Treatment

Answer 17

-Anti-Resorptive Agents
Bisphosphonates
Denosumab
Raloxifene
Calcitonin
Estrogens
-Anabolic Agents
Teriparatide
Romosozumab

Question 18

Bisphosphonates

Answer 18

Alendronate
Risedronate
Zoledronate [Reclast]

Question 19

Bisphosphonates MOA

Answer 19

• Pyrophosphate analogs with high affinity for bone at Ca-P interface
• BPs bind to active sites of bone remodeling  direct inhibitory effects on OC

Question 20

Bisphosphonates Need-to-know

Answer 20

• Bad absorption orally (1-10%)
• ADRs:GI irritation, esp. esophagitis & osteonecrosis of the jaw
• most effective drugs for treatment and prevention of osteoporosis

Question 21

SERMS

Answer 21

• selective estrogen receptor agonists (agonists @ bone/liver, inactive antagonist @ uterus, anatagonist @ breast)
• Raloxifene

Question 22

SERMS MOA

Answer 22

• SERMs reduce risks of osteoporotic fractures, but less efficacy than estrogen (or bisphosphonates)
• SERM + estrogen combo showed greater increases in BMD than SERM alone
• Reduced risk of breast cancer and coronary events
• Worsening of menopausal vasomotor symptoms, leg cramps with raloxifene

Question 23

SERM Role in Osteoporosis:

Answer 23

Choice in patient intolerant of bisphosphonates or at increased invasive breast cancer risk

Question 24

Estrogen role in osteoporosis

Answer 24

limited to women with significant vasomotor symptoms who are not at risk for heart disease

Question 25

Teriparatide

Answer 25

synthetic amino terminal human PTH fragment [AA 1-34]

Question 26

Teriparatide MOA

Answer 26

Only agent for treatment of osteoporosis that stimulates bone formation - all other treatments are antiresorptive - Continuous high levels: bone demineralization and osteopenia - Intermittent administration: inc osteoblastic activity and bone formation

Question 27

Teriparatide Need-to-know

Answer 27

- Daily subcutaneous dose - ADRs: Nausea, headache, dizziness, muscle cramps - Role in osteoporosis: Treatment of severe osteoporosis in postmenopausal women and men at high risk of fractures

Question 28

Denosumab MOA

Answer 28

- Humanized monoclonal antibody against RANKL - reduces osteoclast activation improving bone mineral density - Generally well tolerated

Question 29

Denosumab role in osteoporosis

Answer 29

Treatment of patients at high risk for fractures - intolerant or non-responsive to other therapies

Question 30

Calcitonin (Calcitonin-Salmon) MOA

Answer 30

- Inhibition of osteoclastic bone resorption | - Modest increase in bone mass – less effective than BPs-PTH

Question 31

Calcitonin Need-to-know

Answer 31

- Given via nasal spray or SC - ADRs: Nausea, hand-swelling, urticaria, increase in cancer rates with long-term use - Role in osteoporosis: Approved by FDA for treatment, but not prevention, of osteoporosis – use is declining

Question 32

Method of hypercalcemia Sx

Answer 32

Elevated plasma Ca++ levels increase threshold for nerve / muscle excitation: muscle weakness, lethargy, coma vice versa in hypocalcemis hence tetany, etc

Question 33

Hypercalcemia of Malignancy Treatment

Answer 33

-Promote Urine Calcium Excretion: Saline Infusion -Inhibit Bone Resorption IV Bisphosphonates Denosumab Calcitonin Plicamycin -Remove Calcium: Dialysis

Question 34

Treatment of Hypercalcemia

Answer 34

- Saline diuresis (± furosemide) - Bisphosphonates (Zoledronate & pamidronate) - Calcitonin: efficacy limited to early admin - Plicamycin: cytotoxic abx, not 1st choice - Glucocorticoids (high dose prednisone): slow response - Phosphates: IV route risky, unless hypophosphatemic

Question 35

Tx of Acute hypocalcemia: Severe hypocalcemic tetany

Answer 35

-Calcium gluconate: treatment of choice, IV over 4-6 hours -Calcium chloride: less desirable, vein irritation, peripheral vasodilation -Calcium gluceptate: can be given intramuscularly. -Oral calcium salts are sufficient (with vitamin D) for milder Sx of aSx NOTE: Serum Mg++ levels should be normalized if low (necessary for PTH actions)

Question 36

Tx of chronic hypocalcemia: Ca++ supp

Answer 36

- Elemental Ca++: carbonate & citrate - Absorption differences among Ca++ salts generally small - Citrate 25% > CO3, less pH dependence – choice if patient on PPIs or H2 antagonists

Question 37

Chronic - Calcium Supplementation ADRs

Answer 37

- usually well tolerated up to 1500-2500 mg/day - GI effects (constipation, intestinal bloating), esp. CaCO3 - Use caution if predisposed to urinary stones (less with citrate)

Question 38

Vit D supp and ADRs

Answer 38

- improves Ca++ abs & suppresses remodeling - Higher doses (10,000 IU/day) appear safe over several months - First signs of toxicity are hypercalciuria and hypercalcemia