Drugs for Parathyroid Disorders

Question 1

what is pagets disease

Answer 1

A bone disorder, of unknown origin, characterized by excessive bone destruction and disorganized repair. Complications include skeletal deformity, musculoskeletal pain, kidney stones, and organ dysfunction secondary to pressure from bony overgrowth

Question 2

what is rickets

Answer 2

The same as osteomalacia, but occurs in the growing skeleton

Question 3

nonhormonal regulators of bone mineral homeostasis

Answer 3

• bisphosphonates
  -fluoride
  -calcmimetics

Question 3

nonhormonal regulators of bone mineral homeostasis

Answer 3

• bisphosphonates
  -fluoride
  -calcmimetics

Question 4

PTH and 1,25(OH)2D ______ the input of calcium and phosphorus from bone into the serum and stimulate bone formation.
1,25(OH)2D also ________calcium and phosphate absorption from the gut.
In the kidney, 1,25(OH)2D _____ excretion of both calcium and phosphorus, whereas PTH _______ calcium but _______ phosphorus excretion.
FGF23 stimulates renal excretion of phosphate.
Calcitonin (CT) is a less critical regulator of calcium homeostasis, but in pharmacologic concentrations can reduce serum calcium and phosphorus by ______bone resorption and stimulating their renal excretion.

Answer 4

increase
increases
decreases
reduces
increases
inhibiting

Question 5

what are 3 regulations of PTH hormone

Answer 5

1. Serum calcium feeds back to parathyroid gland
2. High calcium
   -Stimulates calcium-sensitive protease in gland
   -Stimulates calcium-sensing receptor (CaSR)
3. Vitamin D
   -Suppresses PTH production
   -Induces CaSR

Question 6

how does parathyroid control LOW serum calcium

Answer 6

Parathyroid releases PTH
Stimulates bone resorption
Increases calcium uptake from GI tract
Increases calcium reabsorption, hydroxylation of vitamin D by kidney
Decreases phosphate reabsorption by renal tubules ↑ Serum Ca

Question 7

how does THYROID control LOW serum calcium

Answer 7

Thyroid decreases release of calcitonin
Decreased bone formation
Increased calcium uptake from GI tract
Increased calcium reabsorption by kidney

Question 8

PTH effects on bone

Answer 8

Net effect of PTH favors bone resorption by osteoclasts
Low, intermittent doses favor bone formation

Question 9

what is the MOA of Terparatide

Answer 9

1-34 active segment of human PTH
-Acts through PTH receptors to produce a net increase in bone formation

Question 10

what is the MOA of Natpara

Answer 10

Genetic engineered full-length (1-84) human PTH

Question 11

list 2 drugs that are PTH preparations

Answer 11

teriparatide
Natpara

Question 12

describe the short-term process of PTH preparations

Answer 12

Short-term, intermittent –> Increased osteoblast number and function –> increased bone formation

Question 13

describe the long-term process of PTH preparations

Answer 13

Long-term, continuous –> Increased osteoclast function —> increased bone resorption

Question 14

what are the uses for PTH preparations

Answer 14

Osteoporosis in postmenopausal women & hypogonadal men
Other osteoporosis in patients at high risk of fracture
Severe osteoporosis not responsive to other drugs

Question 15

what are the contraindications for PTH preparations

Answer 15

Patients at increased risk of bone tumors [osteosarcoma]
Paget’s disease of bone, elevated alkaline phosphatase

Question 16

what are the Adverse effects for PTH preparations

Answer 16

Carcinogenesis (osteosarcoma)
Orthostatic hypotension
Kidney stones (assoc. with elevated serum calcium]
Diarrhea, nausea
GERD
Muscle cramps

Question 17

what is the uses of Terparatide

Answer 17

osteoporosis

Question 18

what is the adverse effects of Terparatide

Answer 18

Hypercalcemia, Hypercalciuria, Osteosarcoma in animals

Question 19

How Does Teriparatide Useful in the Treatment of Osteoporosis?

Answer 19

Increases bone formation
Cessation associated with rapid bone loss
-Follow treatment with bisphosphonate or other anti-
resorptive agent
Especially useful in:
-Post-menopausal women with high fracture risk

Question 20

calcitonin is secreted by

Answer 20

parafollicular (C) cells of thyroid gland

Question 21

calcitonin mediates____________ effects of PTH

Answer 21

OPPOSITE

Question 22

calcitonin mediates____________ effects of PTH

Answer 22

OPPOSITE

Question 23

MOA of calcitonin

Answer 23

Inhibits bone resorption

Question 24

uses of calcitonin

Answer 24

Osteoporosis

Question 25

adverse effects of calcitonin

Answer 25

rhinitis

Question 26

MOA for calcium & phosphate

Answer 26

Bone mineralization

Question 27

uses for calcium & phosphate

Answer 27

Osteoporosis, osteomalacia, Ca & P deficiencies

Question 28

adverse effects for calcium & phosphate

Answer 28

constipation

Question 28

adverse effects for calcium & phosphate

Answer 28

constipation

Question 29

MOA for Cholecalciferol [D], Ergocalciferol, Calcitriol [active D]

Answer 29

Regulates gene transcription via the vitamin D receptor to produce the effects

Question 30

USES for Cholecalciferol [D], Ergocalciferol, Calcitriol [active D]

Answer 30

prophylaxiss & Rx. Vitamin D deficiency, Osteoporosis, Osteomalacia, Psoriasis, calcium def. (renal insufficiency (must use calcitriol)

Question 31

adverse effects for Cholecalciferol [D], Ergocalciferol, Calcitriol [active D]

Answer 31

Hypercalcemia Hypercalciuria (kidney stones) Cholestyramine inhibits absorption Phenytoin and barbiturates increase metabolism

Question 32

MOA of Alendronate [Bisphosphonate]

Answer 32

Inhibition of osteoclast mediated bone resorption

Question 33

uses of Alendronate [Bisphosphonate]

Answer 33

Osteoporosis, Paget’s disease

Question 34

adverse effects of Alendronate [Bisphosphonate]

Answer 34

Esophageal irritation, osteonecrosis of the jaw

Question 35

adverse effects of Denosumab

Answer 35

Osteonecrosis of the jaw, risk of infection

Question 36

uses of Denosumab

Answer 36

osteoporosis

Question 37

MOA of Denosumab

Answer 37

Immunoglobulin G2 monoclonal antibody against RANKL Prevents RANK activation of NF-𝜅B Inhibits gene expression for formation of osteoclasts Inhibits osteoclast function Mimics osteoprotegerin [OPG] Increases osteoclast apoptosis

Question 38

MOA of Raloxifene

Answer 38

Selective Estrogen Receptor Modifier - SERM Estrogen agonist effect in bone + antagonist in breast and endometrium

Question 39

uses of Raloxifene

Answer 39

Osteoporosis in postmenopausal women

Question 40

adverse effects of Raloxifene

Answer 40

Hot flashes, thromboembolism Menopausal symptoms Increased risk of stroke, PE, DVT

Question 41

MOA of Cinacalcet

Answer 41

Increases sensitivity of calcium sensing receptor (CaSR) of parathyroid gland ↓PTH for a given level of serum calcium (reduced sensitivity) ↓ PTH & serum calcium

Question 42

uses of Cinacalcet

Answer 42

Hyperparathyroidism

Question 43

adverse effects of Cinacalcet

Answer 43

Hypocalcemia

Question 44

vit D2

Answer 44

ergocalciferol , plant source

Question 45

cholecalciiferol

Answer 45

Vit D3

Question 46

1,25 dihydroxy vitamin D

Answer 46

calcitrol

Question 47

________ stimulates the renal alpha 1 hydroxylation of vit. D

Answer 47

PTH

Question 48

Calcium carbonate & Calcium citrate drug interactions:

Answer 48

Decrease the absorption of ciprofloxacin, fluoride, phenytoin, levothyroxine, and tetracycline, so calcium supplements should be taken at least 2 hours before or after taking these drugs.

Question 49

1st/ 2nd or 3rd gen Etidronate

Answer 49

First Generation (least potent)

Question 50

1st/ 2nd or 3rd gen: Alendronate Pamidronate Risedronate Tiludronate

Answer 50

Second Generation (~100X more potent)

Question 51

1st/ 2nd or 3rd gen: Ibandronate Zoledronic Acid

Answer 51

Third Generation (~1000X more potent)

Question 52

MOA for Tiludronate

Answer 52

Causes osteoclast to detach from bone by inhibiting tyrosine phosphatase Reduces proton pump activity

Question 53

Bisphosphonates (Inhibit Osteoclast Activity) SIDE EFFECTS (5)

Answer 53

1. Esophageal erosion - Remain upright after ingestion 2. GI distress - Pamidronate most common, alendronate, risedronate least 3. Atypical femur fractures with long-term use - Preceded by dull, aching pain in thigh or groin 4. Osteonecrosis of jaw - High doses and poor oral health 5. Calcium supplements and antacids decrease absorption - 2-hour rule

Question 54

MOA of sodium fluoride

Answer 54

Increases bone crystal size and makes more resistant to resorption Increases bone formation Limited use Tends to cause osteosclerosis No effect on osteoporotic fractures

Question 55

MOA of sodium fluoride

Answer 55

Increases bone crystal size and makes more resistant to resorption Increases bone formation Limited use Tends to cause osteosclerosis No effect on osteoporotic fractures

Question 56

what drug : Antagonizing vitamin D-stimulated intestinal calcium transport - Osteoporosis

Answer 56

glucocorticoids

Question 57

what drug : Promotes osteoclast apoptosis and increases bone formation

Answer 57

Strontium Ranelate

Question 58

Gallium Nitrate MOA

Answer 58

Managing the hypercalcemia in malignancies and Paget’s disease. It acts by inhibiting bone resorption. Adverse effect: Nephrotoxicity

Question 59

Plicamycin (mithramycin -uses)

Answer 59

Used to reduce serum calcium and bone resorption in Paget’s disease and hypercalcemia Adverse effects: Thrombocytopenia, hemorrhage, hepatic and renal damage

Question 60

what is the function of Sevelamer

Answer 60

The phosphate-binding gel is used in combination with calcium supplements and dietary phosphate restriction to treat hyperphosphatemia, a common complication of renal failure, hypoparathyroidism, and vitamin D intoxication.