First Semester 4th exam PT Deck Flashcards
What is the function of Vitamin D in the gut?
It increases absorption of Ca and Phosphorus from the Gut into the serum.
What function do Parathyroid and Vit D serve at the bone?
They both either promote reabsorption of Ca and P to the serum, or to create more bone using Ca and P in the serum. This serves to maintain equilibrium with the serum, constantly remodeling the bones.
What function does Calcitonin serve at the bone?
It inhibits reabsorption of Ca and P from the bone to the serum.
What is the function of Vit D in the Kidney?
It prevents the excretion of CA and P.
What is the Function of PTH at the Kidney?
It inhibits Ca excretion, but promotes P excretion.
What is the function of CT at the Kidney?
It promotes the excretion of both Ca and P.
What is the function of FGF23 (Fibroblast Growth Factor 23) at the kidney?
It promotes the excretion of P.
What is the relationship between Vit D and PTH?
In the Kidney Vit D is changed to the active form with the assistance of PTH, and the active D will inhibit the release of PTH at the Parathyroid.
What is the MOA of Cinacalcet?
It is a Calcimimetic, its mimics Calcium on the CaSR sensors making them more sensitive to calcium and decreasing PTH.
What is Cinacalcet indicated and contraindicated for?
Indications
Secondary Hyperparathyroidism due to CKD
Primary hypercalcemia in primary hyperparathyroidism or parathyroid carcinoma.
C/I
Hypocalcemia
What are Cinacalcet’s ADRs?
N / V / D
High incidence (25% of PTs)
What are Osteopenia and Osteoporosis?
Reduced bone mineral density (BMD), bone quality and bone strength due to various risk factors that lower bone formation or increase bone reabsorption.
Old age
Post-menopause
Medications such as anticoags
Low Calcium
What is the MOA of Teriparatide and Abaloparatide?
It increases osteoblast activity. At a low intermittent dose, it causes a transient serum increase in PTH and new bone formation.
What are the indications C/I for Teriparatide and Abaloparatide?
Indications
Moderate-severe osteoporosis
Hypoparathyroidism
C/I
Continuous infusion leads to osteoclast rather than osteoblast activity.
Max 2 years due to the risk of osteosarcoma
What are the ADRs of Teriparatide and Abaloparatide?
Mild hypercalcemia; hyperuricemia
Orthostatic Hypotension (within first 4 hours or few doses, body will adjust)
Boxed Warning for Teriparatide
Risk of osteosarcoma if taken more than 2 years
Vitamin D’s (Anabolic)
Cholecalciferol (D3)
Ergocalciferol (D2)
Doxcalciferol
Calcitriol (“active” form)
Can Everyone Drive Cars
Vit D’s MOA/Use
Used for Osteoporosis
Kidney stones in the presence of high Phosphorus levels
Vit D’s misc
D2 (ergo) -> more concentrated formulation allows higher doses
Doxercalciferol metabolized to D2 in liver (no kidney requirement)
Anti-Resorptive Drugs
Calcium (various formulations/salts)
Calcitonin
Estrogens; Raloxifene
Estrogens/bazedoxifene
Bisphosphonates (-dronate/dronic acid)
Denosumab
Calcium
Incorporated into hydroxyapatite crystals of bone via osteoblast activity
- Increased bone mineralization with P
Reduces hyperPTism that occurs with age
-Increased calcium levels reduce PTH release
Adverse effects
- Constipation
- Kidney Stones (hypercalciuria)
Calcitonin
Anti-resorptive peptide hormone secreted in response to high serum calcium
Activation of calcitonin receptor on osteoclasts inhibit osteoclast activity
-Result -> less Ca/P release from bone into serum
Activation of calcitonin receptor on kidney reduces reabsorption of calcium
-Result-> increases calcium excretion
Calcitonin/Miacalcin (Salmon)
Used in hypercalcemia, osteoporosis, and Paget’s
Slight analgesic effect-> intranasal more rapid
-Unclear mechanism in Pain pathway
Adverse effects:
Nasal Stuffiness
Nausea/vomiting; flushing; salty taste; rash
Anaphylactic allergic reaction
Potential for neutralizing antibodies to develop
Efficacy decrease over time
Estrogens
Reduce osteoclast activity
Generally, do not reverse bone density loss that has already developed
Primary role in bone disorders in the prevention of osteoporosis associated with menopause
Can decrease vasomotor symptoms (hot flashes)
ADEs
Can increase risk of uterine and breast cancer
Can increase risk of thrombosis
More to come in Gonadal Hormones lecture
Raloxifene
Selective Estrogen Receptor Modulator (SERM)
(Considered a mixed agonist/antagonist)
Less efficacious than estrogens in osteoporosis
Activates estrogen receptors in bone
-increased BMD; reduced resorption
No appreciable effect on uterus; opposes estrogen effect in breast/blood (sometimes considered antagonist at all three)
- No increased uterine cancer risk (like seen with estrogens)
- Decreased breast cancer risk; lower thrombosis risk
Can increase vasomotor symptoms (hot flashes)
Bazedoxifene
SERM-> similar to raloxifene
Reduces endometrial overgrowth that can occur with estrogens (similar to progesterone)
-Can only be used in women with intact uterus
May have estrogen-like effects on breast/blood
-Contraindicated in breast cancer or HX of thrombosis
Estrogen component provides benefit in hot flashes
-Raloxifene can worsen hot flashes
Currently only available in combination with conjugated estrogens as brand name Duavee
Indicated to treat menopausal hot flashes and to prevent post-menopausal osteoporosis
Bisphosphonate Agents
Alendronate
Etidronate
Ibandronate
Pamidronate
Risedronate
Zoledronic acid
-dronate/dronic acid
Bisphosphonate MOA
Bind serum calcium salts -> complex becomes incorporated into the bone matrix
Complex ingested by osteoclasts-> inhibit osteoclast activity by inhibiting protein synthesis
- Inhibits formation/aggregation/dissolution of crystals
- Can also cause apoptosis of osteoclast
Dosing regimens vary based on agent but some can be dosed much less frequently b/c of matrix incorporation
Drugs are preferentially localized to site of resorption on bone-> “anti-resorptive”
Bisphosphonate ADE/DDIs
Poor oral absorption (SQ/IV preference)
Bind Calcium-> drug/food interactions
Adverse effects
Hypocalcemia; hypophosphatemia
Myalgia
Osteonecrosis of the jaw
-Painful swelling of jaw bone
Erosive esophagitis (oral dosage forms)
- Increased risk of GERD
- Proper counseling required
Denosumab
Monoclonal antibody; inhibits action of RANKL
Reduces bone resorption by blocking osteoclast activation, formation, and survival
Treats osteoporosis (men, post-menopausal, steroid-induced); also used to treat certain cancers (Xgeva)
Particularly preferred in high fracture risk PTs
Favorable dosing-> SC once every 6 months
ADEs:
Concern: increased risk of infection b/c of RANKL being present on cells in immune system
Also similar concern for ONJ and hypoCa/hypoP as with bisphosphonates
