Block 4: Vitamin D and Potassium Binders

Question 1

Describe the how calcium and phosphate maintain homeostasis?

Answer 1

Question 2

Describe the dysregulation of mineral metabolism?

Answer 2

Question 3

What is the pharmacological effects of vit D and analogues?

Answer 3

↑ serum (Ca2+) → suppress PTH secretion and ↑ intestinal absorption

Question 4

What is the pharmacological effects of phosphate binding agents?

Answer 4

↓ intestinal absorption of phosphate by binding to dietary phosphate in the gut → lowering serum phosphate

Question 5

What is the pharmacological effects of calcimimetics?

Answer 5

↑ sensitivity of Ca-SR (sensing receptor) in parathyroid glands to Ca2+ → ↓ PTH

Question 6

Where is vitamin D obtained from?

Answer 6

Diet or sunlight-triggers synthesis in skin

Question 7

Where does the production of vitamin D occur?

Answer 7

Liver, 25-hydroxylated → 25-OH vitamin D (Calcidiol): Prohormone → Calcifediol

Question 8

How is vitamin D produced in organs other than the liver?

Answer 8

Kidney or other tissues: 1a-hydroxylated → 1, 25-OH2 Vit D (Calcitriol): Active

Question 9

Too much or suprophysiological doses of Calcitriol → ___

Answer 9

Hypercalcemia

Question 10

Unlike natural vitamin D, calcitriol analogs have _____ ____ effect?

Answer 10

Minimized hypercalcemic

Question 11

What organs does vitamin d and analogs act on?

Answer 11

Intestine: ↑ both Ca2+ and phosphate absorption
Kidney: ↓ renal excretion of Ca2+ and ↑ tubular reabsorption of P
Bone: PTH, ↑ bone formation

Question 12

What are the therapeutic uses of vitamin D and analogues?

Answer 12

Secondary hyperparathyroidism, psoriasis, osteoporosis

Question 13

What is the MOA of vitamin D?

Answer 13

1. Mediated by binding to membrane (mVDR) or nuclear (VDR) → slow genomic action
2. Rapid nongenomic action

Question 14

Where are vitamin D receptors found?

Answer 14

1. PT gland
2. Intestine
3. Kidney
4. Bone
5. Other (prostate, endothelium, immune cells)

Question 15

What are the non genomic action of Vit D and analogues?

Answer 15

1. ↑ intestinal absorption of Ca and P
2. ↓ renal excretion of Ca and ↑ tubular reabsorption of P
3. ↓ PTH
4. ↑ bone resorption/formation

Question 16

Describe the analogs of vitamin D?

Answer 16

Question 17

What are vitamin D products?

Answer 17

1. Ergocalciferol: Vitamin D2 – lower affinity to Vit D binding protein
2. Cholecalciferol: Vitamin D3
3. Calcitriol: Active vitamin D (1,25-dihydroxy-Vitamin-D)

Question 18

What are the ADRs of vitamin D products?

Answer 18

1. Hypercalcemia
2. w/ or w/o hyperphasphatemia

Question 19

What are the vitamin D analogues? Differences?

Answer 19

1. Doxercalciferol: Prodrug - activated by hepatic 25-hydroxylation to active 1α,25-(OH)2D2.
2. Paricalcitol: ↓ serum PTH levels without producing hypercalcemia or altering serum phosphorus.

Question 20

Indications for vitamin D analogs?

Answer 20

Secondary hyperparathyroidism

Question 21

What are the types of phosphate binders?

Answer 21

Calcium-based and non-calcium

Question 22

What are calcium based PB?

Answer 22

Calcium (carbonate, acetate, citrate)

Question 23

What are the non-calcium PB?

Answer 23

1. Salts of Al, Mg, lanthanum, and Iron
2. Sucroferric oxyhydroxide
3. Sevelamer HCl or Carbonate

Question 24

What is the MOA of calcium-based PB?

Answer 24

1. Bind to dietary phosphorus → form insoluble Ca-P complex → eliminated through feces, ↓ serum P
2. Positive Ca2+ balance

Question 25

What is is the most common CB-PB? Why?

Answer 25

Calcium carbonate is inexpensive, effective, and readily available

Question 26

ADRs of calcium carbonate use?

Answer 26

High dose → hypercalcemia → risk to vascular calcifications and stiffness

Question 27

What is the MOA of lanthanum carbonate?

Answer 27

Bind to P → insoluble lanthunum phosphate complex → ↓ absorption of dietary P → ↓ serum P

Question 28

What is MOA of ferric citrate?

Answer 28

Ferric iron binds dietary phosphate in the GI tract → precipitates as ferric phosphate → not absorbed so excreted in the stool.

Question 29

What is the MOA of sucroferric oxyhydroxides?

Answer 29

The bound phosphate is eliminated with feces, insoluble, not absorbed and not metabolized

Question 30

Describe the phosphate binding of sucroferric oxyhydroxides?

Answer 30

Phosphate binding occurs by an exchange between hydroxyl groups in sucroferric oxyhydroxide and the phosphate in the GI environment

Question 31

What are the components of sucroferric oxyhydroxides?

Answer 31

Mixture of polynuclear iron (III)-oxyhydroxide, sucrose, and starches

Question 32

What are the salt forms of sevelamer?

Answer 32

Hydrochloride and carbonate (acid-base balance)

Question 33

MOA of sevelamer?

Answer 33

Nonabsorbable hydrogel → binds to P

Question 34

ADR and CI of Sevelamer?

Answer 34

ADR: less likely to induce hypercalcemia CI: presense fo bowel obstruction or hypersensitivity

Question 35

What are calcimimetics?

Answer 35

Act as positive allosteric modifiers of calcium sensing receptors (Ca-SR)

Question 36

What is the primary role of Ca-SR?

Answer 36

Regulates PTH secretion to changes in extracellular Ca2+

Question 37

What is the MOA of calcimimetics?

Answer 37

Enhance sensitivity of Ca-SR to extracellular Ca2+ → Lowers Ca2+ due to PTH suppression

Question 38

What are the classes of calcimimetics?

Answer 38

Type 1: Direct agonist Type 2: positive allosteric activator

Question 39

What is an example of a type 2 calcimimetic?

Answer 39

Cinacalcet

Question 40

What is MOA of Cinacalcet?

Answer 40

Enhances signal transduction by inducing conformational change in receptor and reducing receptor's threshold for Ca2+

Question 41

What are the disadvantages of use aluminum PB?

Answer 41

Chronic use to Parkinsons, neurotoxic, hepatotoxic

Question 42

How is cinacalcet eliminated?

Answer 42

CYP3A4, CYP2D6, and CYP1A2 → eliminated renally

Question 44

Does cinacalcet require a dosage adjustment?

Answer 44

Moderate to severe hepatic impairment but not in renal impairment

Question 45

DDI of cinacalet?

Answer 45

Strong CYP3A4 and CYP2D6 substrates

Question 46

Indications for cinacalet?

Answer 46

1. Secondary hyperparathyroidism in CKD 2. Hypercalcemia from PT carcinoma 3. Primary hyperparathyroidism

Question 47

What is Sodium polystyrene sulfonate? MOA?

Answer 47

Cation-exchange resin Swells → allows exchange of ions between Na+ on resin and K+ Bound-K+ moves through intestine → feces Not absorbed into systemic circulation

Question 48

ADRs of SPS?

Answer 48

Hypernatremia, hypocalcemia, hypomagnesemia

Question 49

What is Patiromer? MOA?

Answer 49

Ca2+ containing non-absorbable K+ binding polymer Distal colon (high free K+): Exchanges Ca2+ for K+, prevents K+ reabsorption → enhances excretion in the feces

Question 50

Indications for Patiromer use? Why

Answer 50

Approved for chronic but not emergency Onset 7-48 hr (slow)

Question 51

What is Sodium zirconium cyclosilicate? MOA?

Answer 51

Non-absorbed, non-polymer inorganic powder with a micropore structure → captures K+ in exchange for H+ and Na+ cations Very selective K+ in comparison to Ca and Mg → reduces free K+ in GI lumen → ↓ serum K+

Question 52

Onset of Sodium zirconium cyclosilicate?

Answer 52

1 h of admin Normokalaemia → 24-48 hr

Question 53

What are the potassium binders?

Answer 53

1. Sodium zirconium cyclosilicate 2. Sodium polystyrene sulfonate 3. Patiromer