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Sem 2 Pharmacology > Week 5 - Calcium and Bone Metabolism 1&2 > Flashcards

Week 5 - Calcium and Bone Metabolism 1&2 Flashcards

1
Q

What are the five areas affected by calcium?

A 
Neurological 
Renal
GIT
Cardiovascular
Other
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2
Q

WHat causes high calcium with a normal or high PTH?

A
  • Primary or tertiary hyperparathyroidism
  • Familial hypocalciuric hypercalcaemia (FHH)
  • Lithium-induced hyperparathyroidism
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3
Q

What causes hypercalcaemia with low PTH?

A
  • A malignancy i.e. lung, breast kidney
  • Sarcoidosis
  • Addison’s disease
  • Thyrotoxicosis
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4
Q

What are the mechanisms of PTH?

A
  • Increases 1alpha-hydroxylation of Vit D
  • Increases intestinal Ca absorption
  • Increases renal Ca conservation
  • Mobilised Ca in the bone
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5
Q

Where is the action of PTH>?

A
  • At the cell surface PTH receptor, found in the renal tubular epithelium leading to renal Ca conservation
  • And in bones in the osteoclast/blasts –> Ca mobilisation
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6
Q

What does too much PTH do?

A

Diminish calcium excretion, increase calcium absorption and increase Ca mobilisation from the bone

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7
Q

What’s most common cause of excess PTH?

A

Parathyroid adenoma

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8
Q

What’s the physiological range of ionised calcium?

A

1.12 - 1.32 mmol/L

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9
Q

What is secondary hyperparathyroidism?

A

High PTH as a compensatory mechanism because of low calcium - Vit D def, Ca def or renal failure

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10
Q

Describe primary hyperparathyroidism aka prevalence, population with it

A

Probably most common cause of hypercalcaemia
- 1:800 prev
2-3x more common in women
90% patients are over 50

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11
Q

How do you present with hyperparathyroidism?

A
  • Many have vague/no symptoms
  • Hypercalcaemia
  • REnal calculi
  • Osteopenia
  • Osteoporosis
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12
Q

WHat do you do if you suspect primary hyperparathyroidism?

A

Sestamibi scan

CT scan

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13
Q

How do you manage hypercalcaemia due to primary hyperparathyroidism? (3)

A
  1. assess severity
  2. Confirm diagnosis via ionised hypercalcaemia, renal calcium conservation and raised intact PTH
  3. Therapy - surgical excision of parathyroid adenoma, bisphosphonates, cinacalcet
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14
Q

Is it beneficial to remove the parathyroid adenoma in mild hyperparathyroidism?

A

Yes - restores bone density, restores bone biochemistry and reduces chance of having vertebral fractures

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15
Q

WHen would you operate with asymptomatic PHPT?

A
  • Calcium high
  • OP on bone density
  • Impaired renal function
  • High renal Ca excretion
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16
Q

What are alternatives to surgery for PHPT?

A
  • Bisphosphonates - transient reduction in Ca levels, increases bone mineral density (decreased turnover and secondary increase in PTH
  • RANK Ligand inhibitors
  • Calcium sensing receptor modulator -
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17
Q

Where are the mutations in familial hypocalciuric hypercalcaemia?

A

In the calcium sensing receptor gene

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18
Q

What happens in FHH?

A

Moderately high PTH and calcium because the calcium sensing receptor doesn’t work –> body can’t tell when it has high calcium, which would normally reduce PTH
–> end up with moderately high calcium and PTH

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19
Q

How do you approach FHH?

A
  • Benign condition - don’t have any problems with the high PTH or calcium
  • Confirm diagnosis of FHH - hypercalcaemia, hypercalciuria, raised intact PTH, family history and genetic testing
  • NO SURGERY
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20
Q

What do you use Cinacalcet for?

A

FHH

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21
Q

How does Cinacalcet work?

A

It inhibits PTH secretion as a calcium sensing receptor modulatory, restoring serum calcium to normal levels

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22
Q

What’s the management of PHPT?

A
  1. Surgical excision
  2. Medical tehrpay with Cinacalcet
  3. Manage osteopososis
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23
Q

What happens in malignant lung cancer hypercalcaemia?

A

Cancer secretes PTH related peptide, which can act on bone and kidney, increasing Ca mobilisation and increasing calcium resorption. This causes hypercalcaemia

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24
Q

What happens in malignant breast cancer / myeloma hypercalcaemia?

A

Bone invasion - cancer metastasizes into the bone. There’s secretion of local factors that cause bone resorption aka bone gets melted

25
Q

What happens to PTH is malignant hypercalcaemia?

A

It’s low

26
Q

How do you treat malignant hypercalcaemia?

A

Rehydration - intravenous saline

  1. Intravenous bisphosphonates - slows bone turnover
    - RANK ligand inhibitors
27
Q

How does hypercalcaemia occur in sarcoidosis?

A

There’s alot of 1a-hydroxylation Vit D in macrophages

28
Q

How do you treat hypercalcaemia in sarcoidosis?

A

Steroids - prednisolone therapy

29
Q

What does a fasting blood metabolic bone study sample give you?

A

Indicates whether hypercalcaemia is a result of:

  • primary hyperparathyroidism
  • FHH
  • malignancy
  • secondary hyperparathyroidism
30
Q

Describe symptoms of hypocalcaemia?

A
  • Neurological - irritability, depression, paranoia, paresthesia, muscle cramps, tetany, papilloedema
  • Cardiovascular - prolonged QT, peaked or inverted T
  • Chvostek’s signs (facial nerve twitch response)
  • Trousseau’s signs (hand cramps at over systolic pressure)
31
Q

What are two ways in which you can become hypocalcemic?

A

Post-parathyroidectomy

-Vit D deficiency

32
Q

How do you treat hypocalcaemia if NOT a result of a parathyroidectomy?

A

Give oral calcium + Vit D3

33
Q

How do you treat hypocalcaemia is post-parathyroidectomy?

A

Oral or IV calcium, or calcitonin and activated Vit D

34
Q

When is peak bone mass achieved? What is it affected by?

A

Early adulthood

  • Sex hormones: puberty, growth, height
  • Intake of calcium, vit D and protein
  • Physical activity/exercise
  • Smoking is detrimental, as is excess alcohol
35
Q

What is a wedge compression fracture?

A

In the vertebrae, very painful, can be debilitating and can lead to kyphosis

36
Q

What is primary OP?

A

Op caused by age or postmenopausal hormone profile in women

37
Q

What is secondary OP?

A

OP caused by factors such as steroid use, inadequate calcium, Vit D, medical conditions/treatments for prostate/breast cancer etc

38
Q

How do you treat OP by increasing Osteoblast activity?

A

Using anabolic agents:

Teriparatide

39
Q

How do you treat OP by decreasing Osteoclast activity?

A
  • Testosterone
  • Estrogen (Raloxifene)
  • Bisphosphonates
  • Denosumab
40
Q

WHats a key consideration when taking bisphosphonates?

A

Poorly absorbed - needs to be delivered on empty stomach

41
Q

How are bisphosphonates given?

A

Either weekly or IV once a year

42
Q

What do bisphosphonates do to BMD?

A

Improve BMD in spine and hip

Decrease fracture risk

43
Q

What’s the downside of bisphosphonates?

A

Treat for five years and RF goes up. These are rare

  • Osteonecrosis of the jaw
  • Atypical femoral fracture: distal transverse femur
44
Q

What is Denosumab?

A
  • A newer drug, single subcutaneous every six months

- Monoclonal antibody which inhibits osteoclast function by blocking RANKL-RANK interaction

45
Q

What is Raloxifene?

A
  • A selective estrogen receptor modulator which decreases bone resorption and increases BMD
  • Also reduces chance of breast cancer
  • But, does increase likelihood thrombobolic disease and maybe post-embolic stroke
46
Q

What is teriparatide?

A
  • A recombinant PTH
  • Daily subcut injection
  • Anabolic agent - stimulates bone formation
  • Strict criteria to take it because it’s so expensive - t-score more than -3.0 and fractures while on therapy
  • Rats got osteosarcomas
47
Q

Why does PTH work as a therapy for OP?

A
  • There’s a differential effect on bone turnover:
    daily supraphysiological exposure to PTH decreases bone resorption, whereas prolonged sustained exposure is detrimental to bone
48
Q

Which anti-inflammatory agents can induce OP?

A

Glucocorticoids - more than 5mg Prednisolone daily increases fracture risk

49
Q

How can you mitigate Glucocorticoid OP risk?

A
  • Supplement calcium and Vit D
  • Minimal effective dose of G
  • Potentially put on bisphosphonates to prevent bone loss/fracture
50
Q

How are testosterone and fractures related?

A

Low testosterone = higher fracture risk

51
Q

What are the differences in giving testosterone to men with pathological hypogonadism, and those without hypogonadism?

A

In those with low testosterone, testosterone relieves symptoms of signs and androgen def and improves secondary sexual characteristics, and BMD.
In men without pathological hypogonadism, the benefit is minimal

52
Q

How can treating prostate cancer increase risk of OP?

A

You deprive of testosterone, which increases risk for osteoporotic fracture and T2 BM
- Need to ensure are on enough Vit D and calcium

53
Q

How can treating breast cancer increase risk of OP?

A

Already gone through menopause, so low estrogen

If you give aromatase inhibitor only, all estrogen gets eaten up, increasing fracture risk as BMD decreases

54
Q

How can you treat breast cancer and preserve/increase BMD?

A

Give aromatase inhibitor AND bisphosphonates aka denosumab

55
Q

WHat are the newer OP treatments?

A
  • Abaloparatide - acts on osteoblasts as a ligand for PTH receptors
  • Romosozumab - sclerostin inhibitor, acting on osteoblasts and reducing resorption
  • Odanacatib - cathepsin K inhibitor - inhibits resorption by acting on osteoclasts, without affecting osteoblasts
56
Q

Is there an interaction between bone and diabetes risk?

A

Osteoblast secreted osteocalcin (OC) is a bone-derived endocrine regulator of glucose homeostasis in mice –> knock it out and mice get T2DM phenotype

In humans, undercarboxylated osteocalcin levels high = lower risk for T2DM, bc you’re making more of the metabolically active OC

57
Q

WHat is Paget’s disease?

A

A mono or poly-ostotic disease of excessive bone resoprtion and formation, which leads to bone pain, deformity and secondary osteoarthritis

58
Q

How do you treat Paget’s disease of bone?

A

With bisphosphonates, looking for symptom relief and normalisation of serum alkaline phosphatase, indicating a normalised bone turnover

Sem 2 Pharmacology (4 decks)

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