Ca2+ pharm Flashcards
FGF action on VIt D
prev. P reabsorption in the kidney
inhibits D
Vit D effects on PTH synthesis
inhibits its synth and release from PT glands
Effects of excess PTH vs low and intermittent doses of PTH stimulation
Excess PTH: increase bone resorption
Low/intermittent doses of PTH stim: stimulate bone formation w/o first increasing bone resorption
*nl: PTH acts on osteoblasts → induce RANKL → increase activity of osteoclast → bone resorption → osteoblastic bone formation
how does 7-dehydrocholesterol → 1,25(OH)2 Vit D?
7-dehydrocholesterol → skin →
Vit D3 → liver →
25 (OH) Vit D → kidney →
1,25 (OH)2 Vit D
Name these Vitamin D supplements: Cholecalciferol: Ergocalciferol: Calcifediol: Calcitriol: Hytakerol:
Cholecalciferol: D3 Ergocalciferol: D2 Calcifediol: 25 OH D3 Calcitriol: 1,25 OH2 D3 Hytakerol: dihydro tachy sterol (1a-OHD3 equiv)
What should be used D3 (Cholecalciferol) or D2 (ergocalciferol)?
D3 - more efficient in elevating serum 25-OHD3
Most useful in pts with liver disease
23-OH D3 (calcifediol)
Alternative for use in disorders that calcitriol is used.
Dihydro tachy sterol
(1a-OHD3 equiv) - req. 25 hydroxylation by kidney to become active
Most useful in pts with decreased synthesis of calcitriol
(chronic renal failure or type 1 Vit D dep rickets)
Give Calcitriol sup - (1,25)
Primary stimulus for calcitonin synth and release
hypercalcemia
Glucagon
TSH/Thyroxine
Adrenergic agents
Gastrin
*calcitonIN keeps ca IN bones
↓ Ca and ↓ PO4
*usefull in tx of osteoporosis and not prevention
Effects of estrogen on osteoblast and osteocytes
E increase osteoblast production of osteoprotegerin (OPG), which competes with RANK to activate osteocytes
- decrease # and activity of osteoclasts by altering cytokine signals from osteoblasts
- E increase osteoclast apoptosis
- E decrease apoptosis of OSTEOCYTES
how can glucocorticoids DECREASE bone density?
- lowers serum Ca by antag. Vit D intestinal abs. → increase PTH →
stim osteoclast activ. - Increase production of RANK ligand by osteoblasts
but Decrease prod of OPG
- activ. osteoclast activ. - Suppress osteoblasts
*note physiologic lvls of gc are req for osteoblast diff. and
GC are used to decrease bone resorption in LARGE doses
- used for chronic hypercalcemia
3 drugs that reduce Osteoclast action and decrease bone resorption
1: bisphosphonates
2/3. Oestrogens, raloxifene
4. Glucocorticoids
Do GC decrease or increase bone resorption in LARGE doses?
decrease bone resorption
(once used for tx of hypercalcemia of malignancy, but bisphosphonates are more effective now)
But , gc can decrease bone density by stimulating osteoclast activity, inhib. osteoblasts (+ osteoclasts)
1 drug that inhibit and stimulates osteoblasts
Inhibited by Glucocorticoids
(it also inhibits Osteoclasts)
Stimulate by Teriparatide
Oestrogens, raloxifene action on osteoclasts
causes apoptosis of osteoclasts
keeps bones from being reab.
Secondary osteoporosis can result from which drugs?
glucocorticoids
phenytoin
Non pharm therapy of osteoporosis
- diet
- exercise - weight bearing
- stop smoking
Bisphosphonate (BP) drugs
the “nates”
Alendronate
Risedronate
Ibandronate
Zoledronate
Have high affinity for bone and have direct inhibitory effects on osteoclasts
Most effective drug for prevention and tx of osteoporosis
bisphosphonates
- induce osteoclast apoptosis
- prevent osteoclast fxn
Denosumab
monoclonal ab against RANKL that reduces osteoclast activation and improves BMD
BPs still preferred
Teriparatide
stimulates bone formation
(PTH analog that if used intermittently (not continuous) somehow increases osteoblastic activ.)
- all other agents are anti-resorptive agents
Thiazide diuretics (HCT) vs Loop diuretics in urinary ca reabsorption
Thiazide: reduce urinary ca
- good for pts with hypercalciuria
Loop: increase urinary ca excretion
Tx for hypercalcemia
- saline diuresis
- bisphosphonates
- calcitonin
- GC
- Phosphates
Thiazide diuretics *reduce urinary ca, not serum
tx for hypocalcemia
- calcium
2. Vit D
Vit D resistant rickets vs Vit D dep rickets tx
Vit D resistant rickets:
- defect in renal phosphate reabsorption
- cant respond to vit D
- give phosphate sup + D2 or calcitriol (1,25)
Vit D dep rickets tx
- enzyme deficiency → low 1,25
- decreased receptors → lack response
- Vit D3 or calcitrol in large doses
- calcium
- note that there are two Vit D dependent rickets type 1 and 2
1. a-hydroxylate deficiency type I
2. Vit D receptor deficiency type II
treatments for SIADH
demeclocycline (block ACH effect)
- IV saline
- fluid restriction
tx for acromegaly
octreotide (somatostatin analog)
pegvisomant (GH receptor antagonist)
Tx for central DI + nephrogenic DI
HCTZ
indomethacin
amilioride
dx for pagets
x ray - blade of grass
sheehan syndrome
ischemic infarct of pituitary following postpartum bleeding; - failure to lactate - absent menstruation cold intolerant - loss pubic hair
low TSH levels
tx for cushings syndrome signs and symptoms due to presence of adrenal tumor
Ketoconazole - inhibits desmolase
- prev production of pregnenolone
Which of glucocorticoid agents must be activated by hepatic conversion of the ketone to the alcohol form at carbon 11 and thus will lack anti-inflammatory activity if given by the topical route?
prednisone
The thyroid gland stores thyroid hormone precursor extracellularly how?
Epithelial cells produce colloid.
Lumen filled with Colloid is surrounded by follicles.
TG makes up the majority of colloids.
Colloid droplets contain precursors and are taken up and processed in the interior of the epithelial cells and result in TH
What type of thyroiditis typically follows a viral illness?
- how does it present?
- test levels?
subacute thyroiditis
- very tender thyroid
- high T4 level and low radioactive iodine uptake
T3 is generated by ___________ in the thyroid cell lysosomes
degradation of iodinated thyroglobulin
What agents are used in treating thyroid storm inhibits the conversion of T4 to T3?
a. Hydrocortisone
b. Propylthiouracil (PTU)
c. Beta-blockers
High calcium levels, low PTH, what do you expect?
Neoplasm secreting PTH-RP
works like PTH to increase calcium levels.
Signs to look for
a. Osteomalacia
b. osteoporosis
c. osteopenia
d. Paget’s disease
a. Osteomalacia – pseudo milk mans fracture
b. osteoporosis – t score more - than 2.5, or fragility fract.
c. osteopenia – bone thinning
d. Paget’s disease – blade of grass, disorg trabecular
She now enters the hospital in a coma. Her serum calcium is 16 mg/dl (normal: 8.5-10.5 mg/dl). Which of the following diuretics (given with normal saline IV fluids) would be most useful to reduce serum calcium in this patient?
Furosemide (loop diuretic)
tx for graves
PTU
methimazole
- to decrease TH synthesis
Dexamethasone/hydrocortazone: prev conversion.
RAI
surgery
tx for prolactinomas
cabergoline or bromocriptine
Regarding dexamethasone test, low and high dose, what results would exclude and which would be consistent with Cushings disease?
Low dose:
suppressed cortisol lvl below 1.8 EXCLUDES cushings D
High dose:
suppressed ACTH is CONSISTENT with cushings D
- giving cortisol suppresses ACTH prod tumor
long term steroid use can result in what that can cause severe hypotension, hyperkalemia, hyponatremia?
adrenal insufficiency
- cant make aldo or cortisol –> low bp
Do you have an aldosterone deficiency in both primary and secondary adrenal insufficiency?
no, only in primary (mainly autoimmune cause)
high ACTH, low cortisol and aldosterone
