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Pharmacology > 18 Bone metabolism > Flashcards

18 Bone metabolism Flashcards

1
Q

18.01 ANTIRESORPTIVE DRUGS

Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - actions

A

decrease bone resorption and increase bone density

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2
Q

18.01 ANTIRESORPTIVE DRUGS

Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - MOA

A

anchor to cell surface proteins on osteoclast membrane by prenylation
prevent osteoclast-mediated bone resorption
incorporated into the bone matrix and ingested by osteoclasts, promoting osteoclast apoptosis

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3
Q

18.01 ANTIRESORPTIVE DRUGS

Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - abs/distrib/elim

A

alendronate, ibandronate, risedronate: given orally with a large amount of water 30min before eating
IV formulations of ibandronate, zoledronate and pamidronate are available
about 50% of absorbed drug accumulates at sites of bone mineralisation, where it remains absorbed onto hydroxyapatite crystals, potentially for months or years, until the bone is resorbed
the free drug is excreted unchanged by the kidneys

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4
Q

18.01 ANTIRESORPTIVE DRUGS

Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - clinical use

A

prevention and treatment of osteoporosis
hypercalcaemia
advanced malignancies with bone metastases
pain relief in Paget’s disease of bone

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5
Q

18.01 ANTIRESORPTIVE DRUGS

Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - adverse effects

A

GIT disturbances, particularly oesophagitis (patient should remain upright for 30min after administration to reduce reflux)
bone pain
osteonecrosis of the jaw (rare) - zoledronate is most potent and more likely to cause osteonecrosis (dental checks and remedial dental work are prerequisites)
atypical femoral fractures with long-term treatment

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6
Q

18.02 ANTIRESORPTIVE DRUGS

Selective oestrogen receptor modulators (SERMs): raloxifene - actions

A

agonist effects on bone and on the CVS but antagonist action on mammary glands and the uterus

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7
Q

18.02 ANTIRESORPTIVE DRUGS

Selective oestrogen receptor modulators (SERMs): raloxifene - MOA

A

like the oestrogens, it inhibits the cytokines that recruit osteoclasts

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8
Q

18.02 ANTIRESORPTIVE DRUGS

Selective oestrogen receptor modulators (SERMs): raloxifene - abs/distrib/elim

A

given orally
undergoes first-pass metabolism
bioavailability ~2%
plasma half-life ~32h

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9
Q

18.02 ANTIRESORPTIVE DRUGS

Selective oestrogen receptor modulators (SERMs): raloxifene - clinical use

A

prophylaxis for postmenopausal osteoporosis and breast cancer

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10
Q

18.02 ANTIRESORPTIVE DRUGS

Selective oestrogen receptor modulators (SERMs): raloxifene - adverse effects

A

risk of thromboembolism

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11
Q

18.03 ANTIRESORPTIVE DRUGS

Calcitonin - actions

A

lowers serum calcium levels and decreases bone resorption

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12
Q

18.03 ANTIRESORPTIVE DRUGS

Calcitonin - MOA

A

decreases calcium and phosphate reabsorption in the kidney
inhibits bone resorption by binding to a specific receptor on osteoclasts, inhibiting their action

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13
Q

18.03 ANTIRESORPTIVE DRUGS

Calcitonin - abs/distrib/elim

A

given by SC/IM injection or nasal spray
plasma half-life 4-12 min
action lasts several hours

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14
Q

18.03 ANTIRESORPTIVE DRUGS

Calcitonin - clinical use

A

hypercalcaemia
Paget’s disease
prevention of postmenopausal osteoporosis

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15
Q

18.03 ANTIRESORPTIVE DRUGS

Calcitonin - adverse effects

A

GIT disorders
facial flushing
taste disturbances
dizziness
muscle pain

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16
Q

18.04 ANTIRESORPTIVE DRUGS

Monoclonal antibody: denosumab - actions

A

inhibits osteoclast formation, function and survival, thereby decreasing bone resorption in cortical and trabecular bone

17
Q

18.04 ANTIRESORPTIVE DRUGS

Monoclonal antibody: denosumab - MOA

A

recombinant human monoclonal antibody (IgG2) that inhibits RANKL, the primary signal for bone resorption

18
Q

18.04 ANTIRESORPTIVE DRUGS

Monoclonal antibody: denosumab - abs/distrib/elim

A

given by SC injection every 6 months

19
Q

18.04 ANTIRESORPTIVE DRUGS

Monoclonal antibody: denosumab - clinical use

A

osteoporosis
can also be used for prevention of skeletal adverse events in patients with bone metastases from solid tumours, as well as to treat bone loss in patients who are receiving hormone-ablation therapy

20
Q

18.04 ANTIRESORPTIVE DRUGS

Monoclonal antibody: denosumab - adverse effects

A

altered bowel habit, dyspnoea, hypocalcaemia, hypophosphataemia, infection, rash, osteonecrosis of the jaw (rare)

21
Q

18.04 ANTIRESORPTIVE DRUGS

Monoclonal antibody: denosumab - special notes

A

calcium and vitamin D deficiencies need to be corrected
dental work before treatment to reduce risk of osteonecrosis of the jaw

22
Q

18.05 ANABOLIC AGENTS

Recombinant form of parathyroid hormone: teriparatide - actions

A

anabolic effects on bone, increasing bone mass, structural integrity and strength

23
Q

18.05 ANABOLIC AGENTS

Recombinant form of parathyroid hormone: teriparatide - MOA

A

stimulation of new bone formation by direct effects on osteoblasts indirectly increasing intestinal absorption of calcium and increasing tubular reabsorption of calcium and excretion of phosphate by kidney
reduces osteoblast apoptosis

24
Q

18.05 ANABOLIC AGENTS

Recombinant form of parathyroid hormone: teriparatide - abs/distrib/elim

A

given SC once daily
half-life ~1h

25
Q

18.05 ANABOLIC AGENTS

Recombinant form of parathyroid hormone: teriparatide - clinical use

A

osteoporosis in postmenopausal women and in men
glucocorticoid-induced osteoporosis
due to concerns regarding long-term safety and efficacy, maximum treatment duration should be 24 months and should not be repeated

26
Q

18.05 ANABOLIC AGENTS

Recombinant form of parathyroid hormone: teriparatide - adverse effects

A

GIT disturbances, dizziness, arthralgia, headache

27
Q

18.06 VITAMIN D PREPARATIONS

Ergocalciferol, alfacalcidol, calcitrol - actions

A

ergocalciferol is a prehormone that gives rise to true hormones, calcifediol and calcitriol, needed in calcium and phosphate homeostasis and in bone metabolism
alfacalcidol is converted rapidly in the liver to 1,25-dihydroxyvitamin D (metabolite of vitamin D, which acts as a regulator of calcium and phosphate metabolism)

28
Q

18.06 VITAMIN D PREPARATIONS

Ergocalciferol, alfacalcidol, calcitrol - MOA

A

calcifediol and calcitriol act on receptors belonging to the steroid superfamily of receptors to increase serum calcium by increasing calcium and phosphate absorption from the intestine and decreasing their excretion by the kidney

29
Q

18.06 VITAMIN D PREPARATIONS

Ergocalciferol, alfacalcidol, calcitrol - abs/distrib/elim

A

given orally
it needs bile salts for absorption

30
Q

18.06 VITAMIN D PREPARATIONS

Ergocalciferol, alfacalcidol, calcitrol - clinical use

A

ergocalciferol: rickets, osteomalacia, hypocalcaemia caused by hypoparathryroidism
alfacalcidol and calcitrol: osteodystrophy of chronic renal failure

31
Q

18.06 VITAMIN D PREPARATIONS

Ergocalciferol, alfacalcidol, calcitrol - adverse effects

A

excessive intake can cause hypercalcaemia
if this persists, renal calculi may result
serum calcium levels should be monitored

Pharmacology (34 decks)

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