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DEMS: Unit III > Parathyroid Pharm > Flashcards

Parathyroid Pharm Flashcards

1
Q

Effect of loop diuretics

A

Dec plasma Ca++

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2
Q

Effect of thiazide diuretics

A

inc plasma Ca++

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3
Q

Use of thiazides

A

hypercalciuria ( to decrease urinary Ca)

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4
Q

Use of loops

A

Hypercalcemia (dec plasma Ca)

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5
Q

Actions of Vit D

A
  • Decreased release of PTH
  • Increased synthesis of Ca++-binding protein and channel
  • Enhanced dietary absorption of Ca++ and PO4
  • Induce RANK ligand in OBs: role in bone mineralization
  • Decreased excretion of Ca++ and PO4
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6
Q

Which agent is more preferred Vit D2 or D3?

A

D3 preferred over D2 (Less efficient in elevating 25-OHD levels than D3 in depletion states)

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7
Q

Best vit D supp in liver disease?

A

Calcifediol (25(OH)D3)

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8
Q

Best vit D supp in renal disease?

A

1,25(OH)2 D3 (calcitriol)

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9
Q

Dihydrotachysterol

A
  • Hepatic 25-OH activation (doesn’t require renal activation) - equivalent to 1-OHD3 in function
  • Can be used in disorders that calcitriol is used
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10
Q

Calcitriol Analogs

A

paracalcitol

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11
Q

paracalcitol MOA and use

A
  • Inhibit PTH release from gland
  • used in secondary hyperparathyroidism
  • Does NOT increase Ca++ absorption/mobilization from bone(NO hypercalcemia)
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12
Q

Calcimimetics MOA

A

bind Ca++-sensing cells on PT gland

- Inc Ca++: reduced release of PTH (no hypercalcemia)

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13
Q

Actions of Calcitonin

A

-Inhibits osteoclastic bone resorption
-Increases excretion of Ca++ and PO4
No clinical findings in deficiency (thyroidectomy) or excess (thyroid carcinoma)

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14
Q

Actions of Estrogen on Bone

A
  • Positive effects on bone mass
  • decrease number and activity of OCs
  • Estrogens increase OB production of osteoprotegerin (OPG, decoy RANKL receptor)
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15
Q

Glucocorticoid Actions on Bone (pharm doses)

A

Glucocorticoids decrease bone density:

  • Lowering of serum Ca++ (antagonize Vit D effect on gut)
  • increase in PTH then stimulates osteoclast activity
  • Increase production of RANK-L by OBs and decrease OPG: inc OC activation & increase bone resorption
  • Risk of osteoporosis when GCs used for inflammation
  • Plus suppressive effects on osteoblasts
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16
Q

Medications causing low bone mass

A

Glucocorticoids,
Excess Thyroid Hormone,
Anticonvulsants

17
Q

Osteoporosis Treatment

A 
-Anti-Resorptive Agents
Bisphosphonates
Denosumab
Raloxifene
Calcitonin
Estrogens
-Anabolic Agents
Teriparatide
Romosozumab
18
Q

Bisphosphonates

A

Alendronate
Risedronate
Zoledronate [Reclast]

19
Q

Bisphosphonates MOA

A
  • Pyrophosphate analogs with high affinity for bone at Ca-P interface
  • BPs bind to active sites of bone remodeling  direct inhibitory effects on OC
20
Q

Bisphosphonates Need-to-know

A
  • Bad absorption orally (1-10%)
  • ADRs:GI irritation, esp. esophagitis & osteonecrosis of the jaw
  • most effective drugs for treatment and prevention of osteoporosis
21
Q

SERMS

A
  • selective estrogen receptor agonists (agonists @ bone/liver, inactive antagonist @ uterus, anatagonist @ breast)
  • Raloxifene
22
Q

SERMS MOA

A
  • SERMs reduce risks of osteoporotic fractures, but less efficacy than estrogen (or bisphosphonates)
  • SERM + estrogen combo showed greater increases in BMD than SERM alone
  • Reduced risk of breast cancer and coronary events
  • Worsening of menopausal vasomotor symptoms, leg cramps with raloxifene
23
Q

SERM Role in Osteoporosis:

A

Choice in patient intolerant of bisphosphonates or at increased invasive breast cancer risk

24
Q

Estrogen role in osteoporosis

A

limited to women with significant vasomotor symptoms who are not at risk for heart disease

25
Q

Teriparatide

A

synthetic amino terminal human PTH fragment [AA 1-34]

26
Q

Teriparatide MOA

A

Only agent for treatment of osteoporosis that stimulates bone formation - all other treatments are antiresorptive

  • Continuous high levels: bone demineralization and osteopenia
  • Intermittent administration: inc osteoblastic activity and bone formation
27
Q

Teriparatide Need-to-know

A
  • Daily subcutaneous dose
  • ADRs: Nausea, headache, dizziness, muscle cramps
  • Role in osteoporosis: Treatment of severe osteoporosis in postmenopausal women and men at high risk of fractures
28
Q

Denosumab MOA

A
  • Humanized monoclonal antibody against RANKL
  • reduces osteoclast activation improving bone mineral density
  • Generally well tolerated
29
Q

Denosumab role in osteoporosis

A

Treatment of patients at high risk for fractures - intolerant or non-responsive to other therapies

30
Q

Calcitonin (Calcitonin-Salmon) MOA

A
  • Inhibition of osteoclastic bone resorption

- Modest increase in bone mass – less effective than BPs-PTH

31
Q

Calcitonin Need-to-know

A
  • Given via nasal spray or SC
  • ADRs: Nausea, hand-swelling, urticaria, increase in cancer rates with long-term use
  • Role in osteoporosis: Approved by FDA for treatment, but not prevention, of osteoporosis – use is declining
32
Q

Method of hypercalcemia Sx

A

Elevated plasma Ca++ levels increase threshold for nerve / muscle excitation: muscle weakness, lethargy, coma
vice versa in hypocalcemis hence tetany, etc

33
Q

Hypercalcemia of Malignancy Treatment

A

-Promote Urine Calcium Excretion: Saline Infusion
-Inhibit Bone Resorption
IV Bisphosphonates
Denosumab
Calcitonin
Plicamycin
-Remove Calcium: Dialysis

34
Q

Treatment of Hypercalcemia

A
  • Saline diuresis (± furosemide)
  • Bisphosphonates (Zoledronate & pamidronate)
  • Calcitonin: efficacy limited to early admin
  • Plicamycin: cytotoxic abx, not 1st choice
  • Glucocorticoids (high dose prednisone): slow response
  • Phosphates: IV route risky, unless hypophosphatemic
35
Q

Tx of Acute hypocalcemia: Severe hypocalcemic tetany

A

-Calcium gluconate: treatment of choice, IV over 4-6 hours
-Calcium chloride: less desirable, vein irritation, peripheral vasodilation
-Calcium gluceptate: can be given intramuscularly.
-Oral calcium salts are sufficient (with vitamin D) for milder Sx of aSx
NOTE: Serum Mg++ levels should be normalized if low (necessary for PTH actions)

36
Q

Tx of chronic hypocalcemia: Ca++ supp

A
  • Elemental Ca++: carbonate & citrate
  • Absorption differences among Ca++ salts generally small
  • Citrate 25% > CO3, less pH dependence – choice if patient on PPIs or H2 antagonists
37
Q

Chronic - Calcium Supplementation ADRs

A
  • usually well tolerated up to 1500-2500 mg/day
  • GI effects (constipation, intestinal bloating), esp. CaCO3
  • Use caution if predisposed to urinary stones (less with citrate)
38
Q

Vit D supp and ADRs

A
  • improves Ca++ abs & suppresses remodeling
  • Higher doses (10,000 IU/day) appear safe over several months
  • First signs of toxicity are hypercalciuria and hypercalcemia

DEMS: Unit III (21 decks)

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