Phosphate Binders Lanthanum calcium carbonate

Phosphate binder PPT for dialysis technology students

1. Phosphate Binders Dr.R.Rao Prethendhira Singh Dept. of Pharmacology SRDCH

2. INTRODUCTION Phosphate is an inorganic molecule consisting of a central phosphorus atom and four oxygen atoms. Phosphate binders are medications used to reduce the absorption of dietary phosphate ; they are taken along with meals and snacks. They are frequently used in people with chronic kidney failure (CKF), who are less able to excrete phosphate, resulting in an elevated serum phosphate. In the steady state, the serum phosphate concentration is determined by the ability of the kidneys to excrete dietary phosphate. 2

3. TYPES Phosphate binders may be simple molecular entities (such as magnesium , aluminium , calcium , or lanthanum salts) Aluminum hydroxide Magnesium-containing antacids Calcium-containing phosphate binders Calcium acetate , Calcium Citrate & Calcium carbonate Noncalcium binders – Sevelamer, Lanthanum Newer – Nicotinamate , Polynuclear iron 9/5/2024 3

4. Mechanism of Action These agents work by binding to phosphate in the GI tract , thereby making it unavailable to the body for absorption. Hence, these drugs are usually taken with meals to bind any phosphate that may be present in the ingested food. They react with phosphate and form an insoluble compound. 9/5/2024 4

5. Phosphate binders: Aluminum hydroxide : The phosphate binder of choice , forming insoluble and nonabsorbable aluminum phosphate precipitates in the intestinal lumen . avoided due to A luminum intoxication due to the gradual tissue accumulation of absorbed aluminum , in the bone , skeletal muscle, and the central nervous system ( CNS ), leading to vitamin D-resistant osteomalacia; a refractory, microcytic anemia; bone and muscle pain; and dementia . Magnesium-containing antacids : avoided in patients with kidney dysfunction because of the risk of hypermagnesemia and the development of diarrhea . 9/5/2024 5

6. calcium-containing phosphate binders: calcium containing (mostly calcium carbonate and calcium acetate ) Use of calcium-containing phosphate binders become less frequent because of concerns about toxicity of calcium accumulation . We generally use non-calcium-containing phosphate binders for: normocalcemic CKD patients CKD patients who are receiving active vitamin D analogs for parathyroid hormone (PTH) suppression . 9/5/2024 6

7. Calcium acetate a more efficient phosphate binder than calcium carbonate as calcium carbonate dissolves only at an acid pH , and many patients with advanced renal failure have achlorhydria or are taking H2-blockers . Calcium acetate, is soluble in both acid and alkaline environments. Calcium citrate avoided in patients with renal failure since citrate can markedly increase intestinal aluminum absorption and aluminum neurotoxicity or the rapid onset of symptomatic osteomalacia . Adverse effects GI effects (nausea, vomiting, constipation) [2] Risk of cardiovascular calcification [3] Risk of hypercalcemia 9/5/2024 7

8. Non-calcium binders: Sevelamer Lanthanum 9/5/2024 8

9. Sevelamer : Sevelamer hydrochloride (Renagel®) and sevelamer carbonate (Renvela®) are nonabsorbable agents that contain neither calcium nor aluminum. cationic polymers that bind phosphate through ion exchange . Relatively less progression of vascular calcification with sevelamer versus calcium-containing phosphate binders among patients with CKD. 9/5/2024 9

10. One problem associated with sevelamer hydrochloride is the possible induction of metabolic acidosis . So, sevelamer carbonate has been developed. it is likely that it will become the preferred binder in this class, but these agents appear to be equivalent in their ability to control phosphate levels. Sevelamer is much more expensive than calcium-based phosphate binders 9/5/2024 10

11. Lanthanum : It is a rare earth element , has significant phosphate-binding properties. The risk of lanthanum accumulation and toxicity , however, appears to be quite low with short-term use. The lower pill burden is one consideration that may favor the use of lanthanum. Sevelamer is commonly initially used over lanthanum since, although equally effective in lowering phosphate, as the long-term data on safety of lanthanum are more limited . 9/5/2024 11

12. NOVEL THERAPIES The current approach to management of hyperphosphatemia is not optimal ; a number of alternative therapies are undergoing evaluation. Nicotinamide Polynuclear iron (III)-oxyhydroxide phosphate (PA21) 9/5/2024 12

13. Nicotinamide : Nicotinamide, a metabolite of nicotinic acid (niacin, vitamin B3). inhibits the Na/Pi co-transport system in the gastrointestinal tract and kidneys and may be effective in lowering phosphate levels in dialysis patients by reducing gastrointestinal tract phosphate absorption . 9/5/2024 13

14. Polynuclear iron (III)-oxyhydroxide phosphate (PA21) : Various doses of polynuclear iron (III)-oxyhydroxide phosphate (PA21) were compared with sevelamer in a randomized , multicenter open-label study, PA21 at doses of 5 and 7.5 g/day produced similar decreases in serum phosphorus to sevelamer dosed at 4.8 g/day. Further study is required to better understand the efficacy and safety of these and related agents in this setting. 9/5/2024 14

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17. Treatment of Hyperphosphatemia Increased and/or extended hemodialysis : Standard dialysis is limited in its ability to remove phosphate . there is only a slow efflux of phosphate from the large intracellular stores into the extracellular fluid, which is undergoing dialysis. lengthening dialysis (within standard dialysis regimens) or using larger , high-efficiency dialyzers is likely to substantially increase phosphate removal. The average standard dialysis removes approximately 900 m g of phosphate. By comparison, extremely long and/or frequent dialysis clears a larger amount of phosphate . For patients with refractory hyperphosphatemia who are willing to accept this form of dialysis, this form of dialysis may be the best approach . 9/5/2024 17

18. Managing Hyperphosphatemia in CKD Patients’ obtain phosphate , calcium , and parathyroid hormone ( PTH ) levels initially and then on an ongoing basis. Among all patients with CKD , avoid aluminum hydroxide except for short-term therapy ( four weeks for one course only) of severe hyperphosphatemia . Among dialysis patients stage 3 to 5 CKD not yet on dialysis 9/5/2024 18

19. Treatment of Hyperphosphatemia Among dialysis patients: maintain serum phosphate levels between 3.5 and 5.5 mg/dL Restrict dietary phosphate to 900 mg/day . patients refractory to maintenance dialysis therapy and diet, recommend the administration of phosphate-binding agents . More frequent and more intensive dialysis can also lower phosphate levels, such as that provided by nocturnal hemodialysis , clears a large amount of phosphate , It is an option among those who are willing to accept this form of dialysis. 9/5/2024 19

20. Treatment of Hyperphosphatemia stage 3 to 5 CKD not yet on dialysis : restrict dietary phosphate to 900 mg/day . serum phosphate levels greater than target levels despite dietary phosphorus restriction after one month , suggest the administration of phosphate binders . 9/5/2024 20

21. THANK YOU 9/5/2024 21