First Semester 4th exam PT Deck

Question 1

What is the function of Vitamin D in the gut?

Answer 1

It increases absorption of Ca and Phosphorus from the Gut into the serum.

Question 2

What function do Parathyroid and Vit D serve at the bone?

Answer 2

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.

Question 3

What function does Calcitonin serve at the bone?

Answer 3

It inhibits reabsorption of Ca and P from the bone to the serum.

Question 4

What is the function of Vit D in the Kidney?

Answer 4

It prevents the excretion of CA and P.

Question 5

What is the Function of PTH at the Kidney?

Answer 5

It inhibits Ca excretion, but promotes P excretion.

Question 6

What is the function of CT at the Kidney?

Answer 6

It promotes the excretion of both Ca and P.

Question 7

What is the function of FGF23 (Fibroblast Growth Factor 23) at the kidney?

Answer 7

It promotes the excretion of P.

Question 8

What is the relationship between Vit D and PTH?

Answer 8

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.

Question 9

What is the MOA of Cinacalcet?

Answer 9

It is a Calcimimetic, its mimics Calcium on the CaSR sensors making them more sensitive to calcium and decreasing PTH.

Question 10

What is Cinacalcet indicated and contraindicated for?

Answer 10

Indications

Secondary Hyperparathyroidism due to CKD

Primary hypercalcemia in primary hyperparathyroidism or parathyroid carcinoma.

C/I

Hypocalcemia

Question 11

What are Cinacalcet’s ADRs?

Answer 11

N / V / D

High incidence (25% of PTs)

Question 12

What are Osteopenia and Osteoporosis?

Answer 12

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

Question 13

What is the MOA of Teriparatide and Abaloparatide?

Answer 13

It increases osteoblast activity. At a low intermittent dose, it causes a transient serum increase in PTH and new bone formation.

Question 14

What are the indications C/I for Teriparatide and Abaloparatide?

Answer 14

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

Question 15

What are the ADRs of Teriparatide and Abaloparatide?

Answer 15

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

Question 16

Vitamin D’s (Anabolic)

Answer 16

Cholecalciferol (D3)

Ergocalciferol (D2)

Doxcalciferol

Calcitriol (“active” form)

Can Everyone Drive Cars

Question 17

Vit D’s MOA/Use

Answer 17

Used for Osteoporosis

Kidney stones in the presence of high Phosphorus levels

Question 18

Vit D’s misc

Answer 18

D2 (ergo) -> more concentrated formulation allows higher doses

Doxercalciferol metabolized to D2 in liver (no kidney requirement)

Question 19

Anti-Resorptive Drugs

Answer 19

Calcium (various formulations/salts)

Calcitonin

Estrogens; Raloxifene

Estrogens/bazedoxifene

Bisphosphonates (-dronate/dronic acid)

Denosumab

Question 20

Calcium

Answer 20

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)

Question 21

Calcitonin

Answer 21

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

Question 22

Calcitonin/Miacalcin (Salmon)

Answer 22

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

Question 23

Estrogens

Answer 23

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

Question 24

Raloxifene

Answer 24

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)

Question 25

Bazedoxifene

Answer 25

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

Question 26

Bisphosphonate Agents

Answer 26

Alendronate

Etidronate

Ibandronate

Pamidronate

Risedronate

Zoledronic acid

-dronate/dronic acid

Question 27

Bisphosphonate MOA

Answer 27

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”

Question 28

Bisphosphonate ADE/DDIs

Answer 28

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

Question 29

Denosumab

Answer 29

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