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imed3003 COPY > Pharmacology - Calcium and Bone Metabolism 1 & 2 > Flashcards

Pharmacology - Calcium and Bone Metabolism 1 & 2 Flashcards

1
Q

What are the symptoms of hypercalcaemia?

A

Neurological: Lethargy, confusion, headache, depression, paranoia, muscle weakness

Renal: Polyuria, polydypsia, nephrocalcinosis

GI: Constipation, anorexia, nausea, vomiting

CVS: Bradycardia, primary HB, and short QT

Other: Soft tissue calcification, pruritis

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2
Q

What causes hypercalcaemia?

A

With normal PTH:

Primary or tertiary hyperparathyroidism

Familial hypocalciuric hypercalcaemia (FHH)

Lithium-induced hyperparathyroidism

With low PTH:

Malignancy

Sarcoidosis

Thyrotoxicosis

Thiazide diuretics

Addison’s disease

Immobilisation

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3
Q

What does PTH do?

A

Increase 1alpha hydroxylation of vitD

Increases intestinal Ca absorption

Action via cell surface PTH receptor:

Renal tubular epithelium: Renal Calcium conservation

Bone (Osteoclast/Osteoblast): Calcium mobilisation

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4
Q

What causes primary hyperparathyroidism?

A

A spontaneous genetic mutation can result in neoplasia of one of the parathyroid glands. This neoplasm is a parathyroid adenoma.

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5
Q

How common is primary hyperparathyroidism?

A

1:800

2 - 3x commoner in women than men

90% of patients are older than 50 years

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6
Q

What are the symptoms of hyperparathyroidism?

A

Usually present with symptoms of hypercalcaemia, renal calculi or osteopenia or osteoporosis

Many patients have vague or no symptoms

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7
Q

How is hypercalcaemia due to primary hyperparathyroidism managed?

A

Assess severity of hypercalcaemia

Confirm diagnosis of primary hyperparathyroidism: Ionized hypercalcaemia, renal calcium conservation, raised intact PTH

Therapy: Surgical excision of parathyroid adenoma.

Bisphosphonates, cinacalcet

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8
Q

How is hypercalcaemia acutely managed? (in severe cases)

A

Acute management: Involves use of intravenous fluids, IV zoledronic acid, and surgery

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9
Q

When should people be operated on for asymptomatic primary hyperparathyroidism?

A

Serum Calcium: When serum calcium is >0.25 mmol/L above the baseline.

Skeletal:If BMD < -2.5 at the spine, hip, NOF, or distal 1/3 radius or vertebral fracture on XR, CT, or MRI

Renal: Cr Cl < 60 ml/min
or 24 h U Ca > 400 mg/d or increased risk stone or presence of nephrolithiasis.

Age < 50

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10
Q

When is surgery advised for primary hyperparathyroidism?

A

If medical surveillance not desired or possible.

History of fracture

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11
Q

How is high PTH treated if the levels of PTH can’t be changed for whatever reason?

A

Bisphopshonates (Alendronate, and zoledronic acid)

RANKL inhibitors (denosumab)

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12
Q

What do bisphophonates do to increased PTH levels?

A

Transient reduction in calcium levels

Increases bone mineral density by reducing turnover

Secondary increase in PTH

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13
Q

What is defective in familial hypocalciuric hypercalcaemia?

A

The calcium sensing receptor which has a mutation that makes the receptor more sensitive.

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14
Q

what is done it it is found that a patient has familial hypocalciuric hypercalcaemia?

A

Nothing it is a benign condition.

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15
Q

How is FHH diagnosed?

A

Hypercalcaemia, hypocalciuria

Raised intact PTH

Family history

Genetic testing

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16
Q

What is cinacalcet?

A

A calcium sensing receptor modulator that inhibits secretion of PTH

Reduces calcium and PTH concentrations

No data for bone density

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17
Q

How is primary hyperparathyroidism managed?

A

Surgical excision

Medical therapy: (Cinacalcet 30 - 60 mg/d)

Treat osteoporosis/osteopenia

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18
Q

How is malignant hypercalcaemia treated?

A

Rehydration: Intravenous saline, +/- frusemide cover

Intravenous bisphosphonates: Zoledronic acid

RANKL inhibitors: Denosumab 120 mg sc

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19
Q

How is hypercalcaemia due to sarcoidosis treated?

A

Prednisolone respponsive

20
Q

What causes hypercalcaemia in sarcoidosis?

A

1alpha-hydroxylation of vitamin D in macrophages resulting in hypercalcaemia, hypercalciuria, suppressed PTH, rasied 1,25 vitD.

21
Q

What happens to calcium levels in people with FHH? What about in their urine?

A

They are elevated but it is diminished dramatically in their urine

22
Q

What are the symptoms associated with hypocalcaemia?

A

Neurological: Irritability depression, paranoia, parasthesia, muscle cramps, carpopedal spasm, laryngeal stridor, tetany papilloedema

Cardiovascular: Prolonged QT, peaked or inverted T

Chvostek’s (facial nerve and Trousseau’s signs (is a clinical sign of existing nerve hyperexcitability (tetany) seen in hypocalcemia)

23
Q

How is hypocalcaemia treated?

A

Autoimmune or post-parathyroidectomy: Ca oral, Ca IV, or calcitriol

VitD deficiency: Ca oral + vitD

Or calcitriol

24
Q

What is osteoporosis defined as?

A

Loss of bone integrity leading to increased fracture risk.

Minimal trauma fractures are the result

25
Q

Why are fracture numbers from osteoporosis higher than they should be?

A

Because it is under-diagnosed, increased fracture related morbidity and mortality.

26
Q

What are the factors that relate to peak bone mass?

A

Sex hormones (puberty, growth (height))

Intake of calcium (vitD and protein)

Physical activity, excercise

Smoking (reduces peak bone mass)

Alcohol (reduces peak bone mass)

27
Q

When is osteoporosis considered primary? How is it treated?

A

When it affects older post menopausal women.

It is treated with bisphosphonates, denosumab, or teriparatide

28
Q

What causes secondary osteoporosis? How is it treated?

A

Inadequate calcium, vitamin D, hyperparathyroidism, hyperthyroidism, malabsorption, coeliac’s disease, renal disease, haematological disease, autoimmune disease, etc

Treated via:

Glucocorticoid use

Hypogonadism

Androgen deprivation

Aromatase inhibition

29
Q

What do the sex hormones do to bone?

A

They decrease bone resorption

30
Q

What other drugs decrease bone resorption?

A

Bisphosphonates

Denosumab

31
Q

What are the risks of using bisphosphonates?

A

Osteonecrosis of the jaw

Atypical femoral fracture

Hypocalcaemia

Oesophageal ulceration

Musculoskeletal pain

Fever

Adynamic bone disease

32
Q

What are the risks of using Denosumab?

A

Osteonecrosis of the jaw

Atypical femoral fracture

Hypocalcaemia

Skin infections

Multiple vertebral fractures on discontinuation

When denosumab is stopped the effects are reversed very quickly.

33
Q

How long should bisphosphonates be used for?

A

Assessment should be based on BMD and T-score. If bone is low density bisphosphonates are better to be continued otherwise a break can be taken.

34
Q

What does raloxifene do?

A

It is a selective oestrogen receptor modulator: 60 mg/d

Decreases bone resorption and increases bone mineral density and decreases vertebral fractures.

Increases risk of endometrium

This method also decreases breast cancer risk, However it increases DVT, and PE as well as stroke risk.

35
Q

What does teriparatide do to BMD?

A

It increases bone formation and in turn BMD while decreasing fracture risk.

It is used only if the other therapies don’t work and if t-score is -3.0 or worse.

36
Q

Why is teriparatide not first line?

A

It has been implicated in osteosarcoma in rats

37
Q

What do glucocorticoids do to BMD?

A

They are associated with decreases in bone formation markers (P1NP and osteocalcin)

Prednisolone is associated with increased fracture risk.

38
Q

What do glucocorticoids do to bone related hormones?

A

Increases amount of RANKL

Decreases amount of OPG

Increases osteoclast lifespan

Induces negative calcium balance by reducing sex steroids

39
Q

How is GC induced osteoporosis treated?

A

Supplement calcium and vitD

Use minimal effective dose of glucocorticoids

High risk or pred> 5 or 7.5 mg/d for 3/12 is the indication for treatment.

Bisphosphonates

Teriparatide (For high risk)

40
Q

What problems are associated with low testosterone in men?

A

Cognitive function drop

Depressive symptoms

Metabolic syndrome

Insulin resistance

Less healthy lifestyle

Less sexual activity

Stroke/TIA

Aortic aneurysm

Frailty

Diabetes CVD

Mortality

FRACTURE

41
Q

How are men with reduced testosterone due to androgen deprivation therapy for prostate cancer treated?

A

Physical activity, adequate calcium, and vitD, pharmacological therapy is used if prior low trauma fracture or BMD

42
Q

How are people on aromatase inhibitors due to breast cancer treated?

A

Bisphosphonates

Denosumab

43
Q

How is hyperparathyroidism related osteoporosis treated?

A

Surgery

Bisphosphonates

44
Q

How is GC related osteoporosis treated?

A

Bisphosphonates

Teriparatide

45
Q

How is male hypogonadism related osteoporosis treated?

A

Testosterone

46
Q

How is androgen deprivation and aromatase inhibition related osteoporosis treated?

A

Bisphosphonates

Denosumab

47
Q

How is paget’s disease treated?

A

Bisphosphonates

imed3003 COPY (48 decks)

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