ic14 - pharmacology

Question 1

MOA of vitamin D (3)

Answer 1

Enhances absorption of dietary calcium, directly stimulates osteoblasts for bone formation, inhibits PTH activity which promotes bone resorption

Question 2

MOA of bisphosphonates

Answer 2

increases osteoclast cell death which slows bone resorption and loss

Question 3

examples of bisphosphonates

Answer 3

risedronate, alendronate, zoledronate

Question 4

significant adverse effects of bisphosphonates

Answer 4

atypical femoral fractures with prolonged use, severe bone, joint or muscle pain, upper GI mucosal irritation; ocular effects (iritis, uveitis), hypocalcemia, osteonecrosis of jaw and external auditory canal

Oral administration: nausea, abdominal pain, heartburn like symptoms
IV administration: flu-like symptoms

Question 5

contraindications for bisphosphonates (4)

Answer 5

Hypocalcemia, abnormalities of esophagus which delay emptying, CrCl <30mL/min, pregnancy and lactation

Question 6

precautions for bisphosphonate use

Answer 6

Upper GI disease, risk factors for jaw/EAC osteonecrosis

Question 7

MOA of Denosumab

Answer 7

Human mab that binds to RANKL → prevents osteoclast development
RANKL normally stimulates the differentiation of pre osteoclasts and promotes the death of old osteoclasts

Question 8

administration of denosumab

Answer 8

Administration: SC injection Q6-monthly, coadministered with 1000mg calcium + ≥400IU Vitamin D OD → because denosumab would suppress osteoclast resorption of calcium to blood so strongly that it can cause hypocalcemia

Question 9

adverse effects of denosumab

Answer 9

Adverse effects: muscle, back, bone, joint pain, NVCD, tiredness, increased cholesterol levels
Rarer AEs: osteonecrosis of jaw, atypical femur fractures

Question 10

should denosumab be discontinued?

Answer 10

Should not discontinue → increased risk of spinal column fractures

Question 11

contraindications for denosumab

Answer 11

Hypocalcemia, pregnancy

Question 12

What must be done before administering SC denosumab?

Answer 12

Check creatinine and 25-OH Vit D levels (impt to exclude renal failure as desonumab is contraindicated with eGFR < 10mL/min)
replete vitamin D
give calcium supplement if patient is renally impaired (would give calcium supplementation in any case)

Question 13

estrogen MOA and indications

Answer 13

Maintains bone density
Increases risk of breast cancer and blood clots → stroke risk
Used in: younger women bone health, or women which require treatment for other menopausal symptoms (not first line for osteoporosis)

Question 14

raloxifene MOA

Answer 14

Estrogen alternative - mixed agonist/antagonist effect
MOA: Selective estrogen receptor modulator → has both agonistic and antagonistic action on receptors depending on tissue type
Mimicks estrogen agonist activity in bones → inhibit accelerated bone resorption both short- and long-term, thereby increasing bone mineral density (BMD), preserving bone structure, and enhancing bone strength.

Question 15

adverse effects of raloxifene

Answer 15

AEs: Hot flashes, increases risk of blood clots

Question 16

calcitonin MOA

Answer 16

Peptide hormone secreted by parafollicular cells of the thyroid gland
Reduces blood calcium (opposing effects of parathyroid hormone) → inhibits osteoclatic bone resorption

Question 17

calcitonin side effects and contraindications

Answer 17

red streaks on skin, injection site reactions, feelings of warmth, redness of face, neck, arms, upper chest

CI: hypersensitivity, hypocalcemia

Question 18

romosozumab MOA

Answer 18

Humanised mouse mab against sclerostin (which suppresses bone formation)
Removes sclerostin inhibition of Wnt signalling pathway which regulates bone growth → increases bone formation and decreases bone resorption