HYPERPHOSPHAT EMIA Group 5

Outlines -Disease manifestation (symptoms,signs), pathogenesis and pathophysiology. -Plan of treatment -Brief detail on pharmacology of the individual important drugs being used.

SIGN AND SYMPTOMS

Signs and symptoms Although most patients with hyperphosphatemia are asymptomatic, they occasionally report hypocalcemic symptoms. muscle cramps tetany perioral numbness or tingling. Othebone and joint pain, pruritus, and rash

PATHOGENESIS

Pathogenesis of hyperphosphatemia Vitamin D intoxication Decreased phosphate excretion because of renal failure

Normal of phosphate homeostas is

Vitamin D intoxicat ion

Decreased phosphate excretion because of renal failure

The Treatment concept of hyperphosphatemia in CKD and phosphate binders

Management of Hyperphosphatemia High phosphate diet restriction Medication: phosphate binders Dialysis intervention: HD or PD

Management of Hyperphosphatemia Limiting dietary phosphate intake: KDOQI : Dietary phosphorus restricted to 800 to 1,000 mg/day when The serum phosphorus levels are elevated (> 4.6 in CKD S3,4 or > 5.5 in CKD S5) The plasma levels of intact PTH are elevated above target range of the CKD stage \ American Journal of Kidney Diseases 2003;42(4):S12-S28.

Management of Hyperphosphatemia

If phosphorus or intact PTH level cannot be control with the target range, despite dietary phosphorus restriction, “Phosphate binders should be prescribed.”

Management of Hyperphosphatemia

Non calcium base binder Management of Hyperphosphatemia

Calcium-based

Calcium carbonate(500 mg,750 mg, 1000 mg) -40% elemental calcium -Dosage regimens: g (elemental calcium) three times daily with meals Mechanism of action Form Insoluble complex in intestines

Calcium acetate -25% calcium element -First-line agent: comparable efficacy to calcium carbonate with half the dose of elemental calcium

Adverse effects - Anorexia - constipation - Flatulence - Nausea - vomiting - Hypercalcemia

Management of Hyperphosphatemia

Non-calcium based phosphate binder

Mechanism of action Bind phosphate in the GI tract to form insoluble complexes and reduces phosphate absorption Aluminum hydroxide

Pharmacokinetics Insoluble, poorly absorbed Al salts in the intestines: hydroxides, Carbonated, phosphates and fatty acid derivatives, are excreted in feces Adverse effects Aluminium toxicity mainly three disorders: - aluminium-induced bone disease - microcytic anemia - neurological dysfunction (encephalopathy).

- Not a first-line agent Reserve for short-term use (4 wk) in patients with hyperphosphatemia not responding to other binders

Management of Hyperphosphatemia

Sevelamer carbonate/ Sevelamer hydrochloride

Mechanism of action Amines exist in a protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding Lower LDL-cholesterol

Pharmacokinetics -Not systemically absorbed -Elimination: Feces Adverse effect - vomiting (22%), nausea(20%), diarrhea (19%), dyspepsea (16%) Dosage tablet(400, 800mg), powder fororal suspension (800mg, 2,400 mg)

Lanthanum carbonate

Mechanism of action form strong complexes with Phosphate that inhibits GI absorption and results in a decrease of serum phosphate and calcium levels

Dosage and indication - Chewable tablet 500, 750, 1000 mg Pharmacokinetics -Half-life, elimination: 53 hr (plasma) -Peak plasma: 1 ng/ml -Bioavailability : 0.002% -Protein bound: 99% -Metabolism : not metabolized -Excretion : Predominantly feces Adverse effect: constipation, abdominal pain, diarrhea, hypertension

Comparison of Phosphate-binding agents

Indication as phosphate-binding agents Phosphate-binding properties Calcium carbonate Calcium citrate Aluminum hydroxide Sevelamer Lantanum

Administration Phosphate-binding properties Calcium carbonateTablets Calcium citrateTablets Aluminum hydroxideSuspension SevelamerPowder for suspension, tablets LantanumTablets

Efficacy

Advantages vs disadvantages

Management of Hyperphosphatemia

Take home message

Management of Hyperphosphatemia

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