Block 4: Vitamin D and Potassium Binders Flashcards
Describe the how calcium and phosphate maintain homeostasis?
Describe the dysregulation of mineral metabolism?
What is the pharmacological effects of vit D and analogues?
↑ serum (Ca2+) → suppress PTH secretion and ↑ intestinal absorption
What is the pharmacological effects of phosphate binding agents?
↓ intestinal absorption of phosphate by binding to dietary phosphate in the gut → lowering serum phosphate
What is the pharmacological effects of calcimimetics?
↑ sensitivity of Ca-SR (sensing receptor) in parathyroid glands to Ca2+ → ↓ PTH
Where is vitamin D obtained from?
Diet or sunlight-triggers synthesis in skin
Where does the production of vitamin D occur?
Liver, 25-hydroxylated → 25-OH vitamin D (Calcidiol): Prohormone → Calcifediol
How is vitamin D produced in organs other than the liver?
Kidney or other tissues: 1a-hydroxylated → 1, 25-OH2 Vit D (Calcitriol): Active
Too much or suprophysiological doses of Calcitriol → ___
Hypercalcemia
Unlike natural vitamin D, calcitriol analogs have _____ ____ effect?
Minimized hypercalcemic
What organs does vitamin d and analogs act on?
Intestine: ↑ both Ca2+ and phosphate absorption
Kidney: ↓ renal excretion of Ca2+ and ↑ tubular reabsorption of P
Bone: PTH, ↑ bone formation
What are the therapeutic uses of vitamin D and analogues?
Secondary hyperparathyroidism, psoriasis, osteoporosis
What is the MOA of vitamin D?
- Mediated by binding to membrane (mVDR) or nuclear (VDR) → slow genomic action
- Rapid nongenomic action
Where are vitamin D receptors found?
- PT gland
- Intestine
- Kidney
- Bone
- Other (prostate, endothelium, immune cells)
What are the non genomic action of Vit D and analogues?
- ↑ intestinal absorption of Ca and P
- ↓ renal excretion of Ca and ↑ tubular reabsorption of P
- ↓ PTH
- ↑ bone resorption/formation
Describe the analogs of vitamin D?
What are vitamin D products?
- Ergocalciferol: Vitamin D2 – lower affinity to Vit D binding protein
- Cholecalciferol: Vitamin D3
- Calcitriol: Active vitamin D (1,25-dihydroxy-Vitamin-D)
What are the ADRs of vitamin D products?
- Hypercalcemia
- w/ or w/o hyperphasphatemia
What are the vitamin D analogues? Differences?
- Doxercalciferol: Prodrug - activated by hepatic 25-hydroxylation to active 1α,25-(OH)2D2.
- Paricalcitol: ↓ serum PTH levels without producing hypercalcemia or altering serum phosphorus.
Indications for vitamin D analogs?
Secondary hyperparathyroidism
What are the types of phosphate binders?
Calcium-based and non-calcium
What are calcium based PB?
Calcium (carbonate, acetate, citrate)
What are the non-calcium PB?
- Salts of Al, Mg, lanthanum, and Iron
- Sucroferric oxyhydroxide
- Sevelamer HCl or Carbonate
What is the MOA of calcium-based PB?
- Bind to dietary phosphorus → form insoluble Ca-P complex → eliminated through feces, ↓ serum P
- Positive Ca2+ balance
What is is the most common CB-PB? Why?
Calcium carbonate is inexpensive, effective, and readily available
ADRs of calcium carbonate use?
High dose → hypercalcemia → risk to vascular calcifications and stiffness
What is the MOA of lanthanum carbonate?
Bind to P → insoluble lanthunum phosphate complex → ↓ absorption of dietary P → ↓ serum P
What is MOA of ferric citrate?
Ferric iron binds dietary phosphate in the GI tract → precipitates as ferric phosphate → not absorbed so excreted in the stool.
What is the MOA of sucroferric oxyhydroxides?
The bound phosphate is eliminated with feces, insoluble, not absorbed and not metabolized
Describe the phosphate binding of sucroferric oxyhydroxides?
Phosphate binding occurs by an exchange between hydroxyl groups in sucroferric oxyhydroxide and the phosphate in the GI environment
What are the components of sucroferric oxyhydroxides?
Mixture of polynuclear iron (III)-oxyhydroxide, sucrose, and starches
What are the salt forms of sevelamer?
Hydrochloride and carbonate (acid-base balance)
MOA of sevelamer?
Nonabsorbable hydrogel → binds to P
ADR and CI of Sevelamer?
ADR: less likely to induce hypercalcemia
CI: presense fo bowel obstruction or hypersensitivity
What are calcimimetics?
Act as positive allosteric modifiers of calcium sensing receptors (Ca-SR)
What is the primary role of Ca-SR?
Regulates PTH secretion to changes in extracellular Ca2+
What is the MOA of calcimimetics?
Enhance sensitivity of Ca-SR to extracellular Ca2+ → Lowers Ca2+ due to PTH suppression
What are the classes of calcimimetics?
Type 1: Direct agonist
Type 2: positive allosteric activator
What is an example of a type 2 calcimimetic?
Cinacalcet
What is MOA of Cinacalcet?
Enhances signal transduction by inducing conformational change in receptor and reducing receptor’s threshold for Ca2+
What are the disadvantages of use aluminum PB?
Chronic use to Parkinsons, neurotoxic, hepatotoxic
How is cinacalcet eliminated?
CYP3A4, CYP2D6, and CYP1A2 → eliminated renally
Does cinacalcet require a dosage adjustment?
Moderate to severe hepatic impairment but not in renal impairment
DDI of cinacalet?
Strong CYP3A4 and CYP2D6 substrates
Indications for cinacalet?
- Secondary hyperparathyroidism in CKD
- Hypercalcemia from PT carcinoma
- Primary hyperparathyroidism
What is Sodium polystyrene sulfonate? MOA?
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
ADRs of SPS?
Hypernatremia, hypocalcemia, hypomagnesemia
What is Patiromer? MOA?
Ca2+ containing non-absorbable K+ binding polymer
Distal colon (high free K+): Exchanges Ca2+ for K+, prevents K+ reabsorption → enhances excretion in the feces
Indications for Patiromer use? Why
Approved for chronic but not emergency
Onset 7-48 hr (slow)
What is Sodium zirconium cyclosilicate? MOA?
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+
Onset of Sodium zirconium cyclosilicate?
1 h of admin
Normokalaemia → 24-48 hr
What are the potassium binders?
- Sodium zirconium cyclosilicate
- Sodium polystyrene sulfonate
- Patiromer
