Drugs for Parathyroid Disorders Flashcards
what is pagets disease
A bone disorder, of unknown origin, characterized by excessive bone destruction and disorganized repair. Complications include skeletal deformity, musculoskeletal pain, kidney stones, and organ dysfunction secondary to pressure from bony overgrowth
what is rickets
The same as osteomalacia, but occurs in the growing skeleton
nonhormonal regulators of bone mineral homeostasis
- bisphosphonates
-fluoride
-calcmimetics
nonhormonal regulators of bone mineral homeostasis
- bisphosphonates
-fluoride
-calcmimetics
PTH and 1,25(OH)2D ______ the input of calcium and phosphorus from bone into the serum and stimulate bone formation.
1,25(OH)2D also ________calcium and phosphate absorption from the gut.
In the kidney, 1,25(OH)2D _____ excretion of both calcium and phosphorus, whereas PTH _______ calcium but _______ phosphorus excretion.
FGF23 stimulates renal excretion of phosphate.
Calcitonin (CT) is a less critical regulator of calcium homeostasis, but in pharmacologic concentrations can reduce serum calcium and phosphorus by ______bone resorption and stimulating their renal excretion.
increase
increases
decreases
reduces
increases
inhibiting
what are 3 regulations of PTH hormone
- Serum calcium feeds back to parathyroid gland
- High calcium
-Stimulates calcium-sensitive protease in gland
-Stimulates calcium-sensing receptor (CaSR) - Vitamin D
-Suppresses PTH production
-Induces CaSR
how does parathyroid control LOW serum calcium
Parathyroid releases PTH
Stimulates bone resorption
Increases calcium uptake from GI tract
Increases calcium reabsorption, hydroxylation of vitamin D by kidney
Decreases phosphate reabsorption by renal tubules ↑ Serum Ca
how does THYROID control LOW serum calcium
Thyroid decreases release of calcitonin
Decreased bone formation
Increased calcium uptake from GI tract
Increased calcium reabsorption by kidney
PTH effects on bone
Net effect of PTH favors bone resorption by osteoclasts
Low, intermittent doses favor bone formation
what is the MOA of Terparatide
1-34 active segment of human PTH
-Acts through PTH receptors to produce a net increase in bone formation
what is the MOA of Natpara
Genetic engineered full-length (1-84) human PTH
list 2 drugs that are PTH preparations
teriparatide
Natpara
describe the short-term process of PTH preparations
Short-term, intermittent –> Increased osteoblast number and function –> increased bone formation
describe the long-term process of PTH preparations
Long-term, continuous –> Increased osteoclast function —> increased bone resorption
what are the uses for PTH preparations
Osteoporosis in postmenopausal women & hypogonadal men
Other osteoporosis in patients at high risk of fracture
Severe osteoporosis not responsive to other drugs
what are the contraindications for PTH preparations
Patients at increased risk of bone tumors [osteosarcoma]
Paget’s disease of bone, elevated alkaline phosphatase
what are the Adverse effects for PTH preparations
Carcinogenesis (osteosarcoma)
Orthostatic hypotension
Kidney stones (assoc. with elevated serum calcium]
Diarrhea, nausea
GERD
Muscle cramps
what is the uses of Terparatide
osteoporosis
what is the adverse effects of Terparatide
Hypercalcemia, Hypercalciuria, Osteosarcoma in animals
How Does Teriparatide Useful in the Treatment of Osteoporosis?
Increases bone formation
Cessation associated with rapid bone loss
-Follow treatment with bisphosphonate or other anti-
resorptive agent
Especially useful in:
-Post-menopausal women with high fracture risk
calcitonin is secreted by
parafollicular (C) cells of thyroid gland
calcitonin mediates____________ effects of PTH
OPPOSITE
calcitonin mediates____________ effects of PTH
OPPOSITE
MOA of calcitonin
Inhibits bone resorption
uses of calcitonin
Osteoporosis
adverse effects of calcitonin
rhinitis
MOA for calcium & phosphate
Bone mineralization
uses for calcium & phosphate
Osteoporosis, osteomalacia, Ca & P deficiencies
adverse effects for calcium & phosphate
constipation
adverse effects for calcium & phosphate
constipation
MOA for Cholecalciferol [D], Ergocalciferol, Calcitriol [active D]
Regulates gene transcription via the vitamin D receptor to produce the effects
USES for Cholecalciferol [D], Ergocalciferol, Calcitriol [active D]
prophylaxiss & Rx. Vitamin D deficiency, Osteoporosis, Osteomalacia, Psoriasis, calcium def. (renal insufficiency (must use calcitriol)
adverse effects for Cholecalciferol [D], Ergocalciferol, Calcitriol [active D]
Hypercalcemia
Hypercalciuria (kidney stones)
Cholestyramine inhibits absorption
Phenytoin and barbiturates increase metabolism
MOA of Alendronate [Bisphosphonate]
Inhibition of osteoclast mediated bone resorption
uses of Alendronate [Bisphosphonate]
Osteoporosis, Paget’s disease
adverse effects of Alendronate [Bisphosphonate]
Esophageal irritation, osteonecrosis of the jaw
adverse effects of Denosumab
Osteonecrosis of the jaw, risk of infection
uses of Denosumab
osteoporosis
MOA of Denosumab
Immunoglobulin G2 monoclonal antibody against RANKL
Prevents RANK activation of NF-𝜅B
Inhibits gene expression for formation of osteoclasts
Inhibits osteoclast function
Mimics osteoprotegerin [OPG]
Increases osteoclast apoptosis
MOA of Raloxifene
Selective Estrogen Receptor Modifier - SERM
Estrogen agonist effect in bone + antagonist in breast and endometrium
uses of Raloxifene
Osteoporosis in postmenopausal women
adverse effects of Raloxifene
Hot flashes, thromboembolism
Menopausal symptoms
Increased risk of stroke, PE, DVT
MOA of Cinacalcet
Increases sensitivity of calcium sensing receptor (CaSR) of parathyroid gland
↓PTH for a given level of serum calcium (reduced sensitivity)
↓ PTH & serum calcium
uses of Cinacalcet
Hyperparathyroidism
adverse effects of Cinacalcet
Hypocalcemia
vit D2
ergocalciferol , plant source
cholecalciiferol
Vit D3
1,25 dihydroxy vitamin D
calcitrol
________ stimulates the renal alpha 1 hydroxylation of vit. D
PTH
Calcium carbonate & Calcium citrate drug interactions:
Decrease the absorption of ciprofloxacin, fluoride, phenytoin, levothyroxine, and tetracycline, so calcium supplements should be taken at least 2 hours before or after taking these drugs.
1st/ 2nd or 3rd gen Etidronate
First Generation (least potent)
1st/ 2nd or 3rd gen:
Alendronate
Pamidronate
Risedronate
Tiludronate
Second Generation (~100X more potent)
1st/ 2nd or 3rd gen:
Ibandronate
Zoledronic Acid
Third Generation (~1000X more potent)
MOA for Tiludronate
Causes osteoclast to detach from bone by inhibiting tyrosine phosphatase
Reduces proton pump activity
Bisphosphonates (Inhibit Osteoclast Activity) SIDE EFFECTS (5)
- Esophageal erosion
- Remain upright after ingestion - GI distress
- Pamidronate most common, alendronate, risedronate least - Atypical femur fractures with long-term use
- Preceded by dull, aching pain in thigh or groin - Osteonecrosis of jaw
- High doses and poor oral health - Calcium supplements and antacids decrease absorption
- 2-hour rule
MOA of sodium fluoride
Increases bone crystal size and makes more resistant to resorption
Increases bone formation
Limited use
Tends to cause osteosclerosis
No effect on osteoporotic fractures
MOA of sodium fluoride
Increases bone crystal size and makes more resistant to resorption
Increases bone formation
Limited use
Tends to cause osteosclerosis
No effect on osteoporotic fractures
what drug : Antagonizing vitamin D-stimulated intestinal calcium transport - Osteoporosis
glucocorticoids
what drug : Promotes osteoclast apoptosis and increases bone formation
Strontium Ranelate
Gallium Nitrate MOA
Managing the hypercalcemia in malignancies and Paget’s disease. It acts by inhibiting bone resorption.
Adverse effect: Nephrotoxicity
Plicamycin (mithramycin -uses)
Used to reduce serum calcium and bone resorption in Paget’s disease and hypercalcemia
Adverse effects: Thrombocytopenia, hemorrhage, hepatic and renal damage
what is the function of Sevelamer
The phosphate-binding gel is used in combination with calcium supplements and dietary phosphate restriction to treat hyperphosphatemia, a common complication of renal failure, hypoparathyroidism, and vitamin D intoxication.
