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(Phase 1) YLL Pharmacology AY 24/25 > MSK - Drugs for Osteoporosis > Flashcards

MSK - Drugs for Osteoporosis Flashcards

1
Q

List THREE major classes of pharmacological therapy for osteoporosis.

A
  1. Dietary supplementation
  2. Antiresorpitive agents
  3. Anabolic agents
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2
Q

List the TWO major dietary supplements for osteoporosis.

A
  1. Calcium
  2. Vitamin D
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3
Q

Why is it essential to ensure sufficient Vitamin D when supplementing calcium for osteoporosis?

A

Vitamin D stimulates the absorption of calcium from the intestine.

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4
Q

List FOUR classes of antiresorptive agents.

A
  1. Bisphosphonates
  2. Anti-RANKL monoclonal antibodies
  3. Oestrogens
  4. Calcitonin
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5
Q

List TWO classes of anabolic agents for the treatment of osteoporosis.

A
  1. Anti-sclerostin monoclonal antibodies
  2. Parathyroid hormone therapies
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6
Q

Name ONE example of an anti-RANKL monoclonal antibody biological drug for the treatment of osteoporosis.

A

Denosumab

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7
Q

What is denosumab? Briefly explain its mechanism(s) of action.

A

Denosumab is an anti-RANKL monoclonal antibody biological drug for the treatment of osteoporosis.

It inhibits the function of RANKL released from osteocytes preventing it from stimulating osteoclast activity.

This reduces osteoclast activity to have an antiresorptive action reducing the breakdown and resorption of bone.

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8
Q

Name ONE example of an anti-sclerostin monoclonal antibody biological drug for the treatment of osteoporosis.

A

Romosozumab

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9
Q

What is romosozumab?

A

Romosozumab is an anti-sclerostin monoclonal antibody biological drug for the treatment of osteoporosis.

It inhibits the function of sclerostin released from osteocytes, preventing it from inhibiting osteoblast activity. Sclerostin is a negative regulator of osteoblast differentiation and activity through inhibition of the canonical Wnt signalling pathway.

This increases osteoblast activity to have an anabolic effect increasing bone growth.

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10
Q

Name ONE example of a parathyroid hormone therapy for osteoporosis.

A

Teriparatide

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11
Q

Name ONE example of an ORAL bisphosphonate for the treatment of osteoporosis.

A

Risedronic acid [risedronate] (alternatively alendronic acid [alendronate] or ibandronic acid [ibandronate])

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12
Q

Name ONE example of an INTRAVENOUS bisphosphonate for the treatment of osteoporosis.

A

Zoledronic acid [zoledronate] (alternatively ibandronic acid [ibandronate])

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13
Q

How should ORAL bisphosphonates be taken? Explain why.

A

Take on an empty stomach with a full glass of plain water (at least 240 ml) and wait 30 min to 1 hour before taking breakfast. Do not lie down for 30 min to 1 hour after taking the medication.

Bisphosphonates have very poor oral bioavailability, and their absorption is significantly reduced by food or mineral water.

Bisphosphonates can cause upper gastrointestinal tract mucosal irritation resulting in acid reflux, nausea, diarrhoea, and abdominal pain.

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14
Q

How frequently should bisphosphonates be administered?

A

Oral: once a week (risedronic acid/ alendronic acid) or once a month (risedronic acid)

Intravenous: once a year (zoledronic acid)

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15
Q

List FIVE common (≥ 1 in 100) adverse effects of ORAL bisphosphonates.

A
  1. Acid reflux (heartburn) and heartburn-like symptoms
  2. Nausea
  3. Musculoskeletal aches
  4. Diarrhoea
  5. Abdominal pain
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16
Q

Name ONE common (≥ 1 in 100) adverse effect of INTRAVENOUS, but not oral, bisphosphonates.

A

Flu-like symptoms

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17
Q

Which common (≥ 1 in 100) adverse effect occurs with both oral and intravenous bisphosphonates?

A

Musculoskeletal aches.

Note that although transient hypocalcaemia occurs with both oral and intravenous routes of administration, clinically significant hypocalcaemia is only common (≥ 1 in 100) for intravenous administration. The risk of hypocalcaemia should always be countered by co-administration of calcium and vitamin D supplementation.

18
Q

List TWO rare (< 1 in 100) but severe adverse effects of bisphosphonates.

A

Atypical femoral fracture and osteonecrosis of the jaw and external auditory canal (for all bisphosphonates).

Worsening renal function (for zoledronic acid).

19
Q

List FOUR contraindications for prescribing oral bisphosphonates.

A
  1. Uncorrected hypocalcaemia
  2. Abnormalities of the oesophagus which may delay emptying
  3. Renal impairment (not recommended: < 35 ml/min; contraindicated: CrCl <30 ml/min)
  4. Pregnancy and lactation.
20
Q

List TWO rare (< 1 in 100) but severe adverse effects common to all antiresorptive agents.

A
  1. Atypical femoral fracture
  2. Osteonecrosis of the jaw
21
Q

List THREE contraindications for intravenous zoledronic acid for prophylaxis of postmenopausal osteoporosis.

A
  1. Renal impairment (contraindicated: CrCl < 35 ml/min)
  2. Vitamin D deficiency - replete vitamin D before infusion
  3. Uncorrected hypocalcaemia - replete calcium and vitamin D before infusion
22
Q

How frequently and by what route is denosumab administered?

A

Once every six months, subcutaneously

23
Q

List TWO common (≥ 1 in 100) adverse effects of denosumab.

A
  1. Musculoskeletal aches
  2. Hypocalcaemia (always co-prescribe calcium and vitamin D daily)
24
Q

List TEN adverse effects of denosumab.

A
  1. Musculoskeletal aches
  2. Hypocalcaemia (always co-prescribe calcium and vitamin D daily)
  3. Nausea/vomiting
  4. Constipation OR diarrhoea
  5. Slight tiredness
  6. Increased cholesterol levels
  7. Cellulitis
  8. Angioedema
  9. Atypical femoral fracture
  10. Osteonecrosis of the jaw
25
Q

List TWO rare (< 1 in 100) but severe adverse effects of denosumab.

A

Any TWO of the following:
1. Atypical femoral fracture
2. Osteonecrosis of the jaw
3. Cellulitis
4. Anaphylactic reaction

26
Q

List THREE contraindications for denosumab.

A
  1. Uncorrected hypocalcaemia (replete calcium and vitamin D before injection)
  2. Pregnancy
  3. Severe renal failure (precaution: CrCl < 30 ml/min; contraindicated: CrCl < 10 ml/min)
27
Q

Why are oestrogens only used for the treatment of postmenopausal osteoporosis when oestrogen treatment is already required for other menopausal symptoms?

A

While oestrogens can maintain bone density, oestrogen therapy can increase the risk of breast cancer and blood clots, which can cause strokes.

28
Q

Name ONE example of a selective oestrogen receptor modulator.

A

Raloxifene

29
Q

Briefly compare and contrast raloxifene with oestrogen.

A

● Raloxifene is a selective oestrogen receptor modulator
● Raloxifene is a mixed oestrogen receptor agonist and antagonist, whereas oestrogen is an oestrogen receptor agonist
● Raloxifene and oestrogen both increase bone density in postmenopausal women
● Raloxifene reduces, whereas oestrogen increases, the risk of some types of breast cancers
● Raloxifene can cause hot flashes, whereas oestrogen reduces hot flashes
● Both raloxifene and oestrogens increase the risk of blood clots

30
Q

List TWO contraindications of calcitonin.

A
  1. Hypersensitivity
  2. Uncorrected hypocalcaemia
31
Q

List NINE adverse effects of calcitonin.

A
  1. Skin rash, red streaks on the skin
  2. Injection site inflammation
  3. Feeling of warmth
  4. Flushing: redness of the face, neck, arms, and occasionally, upper chest
  5. Diabetogenic effect
  6. GI disturbances and abdominal pain
  7. Dizziness, tingling of the hands, unpleasant taste, tremor
  8. Urinary frequency
  9. Anaphylactic shock (potentially fatal)
32
Q

List THREE contraindications for romosozumab.

A
  1. Hypersensitivity
  2. Uncorrected hypocalcaemia
  3. History of myocardial infarction or stroke (within the preceding year)
33
Q

List FOUR adverse effects of romosozumab.

A
  1. Increased risk of MI and stroke
  2. Transient hypocalcemia
  3. Hypersensitivity reactions (e.g. angioedema, erythema multiforme, urticaria, dermatitis, rash).
  4. Rarely: osteonecrosis of the jaw, atypical low-energy or low trauma fracture of the femoral shaft.
34
Q

How frequently and by what route is romosozumab administered?

A

Once a month, subcutaneously

35
Q

Many drugs for osteoporosis can cause hypocalcaemia and/or are contraindicated in uncorrected hypocalcaemia.

Name ONE drug for osteoporosis that can cause HYPERCALCAEMIA.

A

Teriparatide (and other parathyroid hormone similars)

36
Q

How frequently and by what route is teriparatide administered?

A

Once daily, subcutaneously for a maximum of 24 months in lifetime

37
Q

Why is it recommended that parathyroid hormone therapies (e.g., teriparatide) are limited to a maximum treatment duration of 24 months in lifetime?

A

There is limited safety data in humans; but in animal models, longer treatments increased the risk of osteosarcomas.

38
Q

List THREE adverse effects of teriparatide.

A
  1. Hypercalcaemia (usual transient and minimal)
  2. Serious calciphylaxis and worsening of previous stable cutaneous calcification
  3. Transient orthostatic hypotension

Additionally:
4. In animal models but not proven in humans, osteosarcoma on long-term treatment

39
Q

List NINE contraindications for teriparatide.

A
  1. Hypersensitivity
  2. Pre-existing hypercalcaemia
  3. Skeletal malignancies or bone metastases
  4. other metabolic bone diseases (e.g. Paget’s disease, hyperparathyroidism)
  5. Unexplained elevations of alkaline phosphatase
  6. Previous implant or external beam radiation therapy to the skeleton
  7. Hereditary disorders predisposing to osteosarcoma
  8. Renal impairment (CrCl < 30 ml/min)
  9. Pregnancy.
40
Q

List SIX classes of medication that can increase the risk of osteoporosis.

A
  1. Serotonin reuptake inhibitors (SSRIs) e.g., escitalopram
  2. Thyroid hormone replacement (when overcompensating and causing hyperthyroidism) e.g., levothyroxine
  3. Glucocorticoid corticosteroids e.g., prednisone
  4. Progesterone agonist contraceptives e.g., depot medroxyprogesterone acetate (DMPA) injections
  5. Hormonal cancer chemotherapy e.g., (a) gonadotropin-releasing hormone (GnRH) agonists used to treat endometriosis and prostate cancer; and (b) aromatase inhibitors used to treat oestrogen-responsive breast cancers
  6. Proton-pump inhibitors (on long-term use) e.g., lansoprazole or esomeprazole.

(Phase 1) YLL Pharmacology AY 24/25 (36 decks)

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