Cation exchange resins

1. Introduction

• Cation exchange resins are insoluble, high-molecular-weight polymers that exchange bound cations for cations present in the surrounding fluid.

• In medicine, they are primarily used to remove excess positively charged ions (e.g., potassium, calcium, sodium) from the body via the gastrointestinal tract.

• The most common therapeutic role is management of hyperkalemia through binding of potassium in the gut and facilitating its excretion in feces.

---

2. Chemical Structure and Properties

• Made of synthetic polymers with a fixed anionic functional group (often sulfonic acid groups) attached to a polymer backbone (commonly polystyrene).

• The resin is in the sodium or calcium form before administration.

• Insoluble in water; works by physical ion exchange without systemic absorption.

• Exchange capacity measured in milliequivalents per gram (meq/g).

---

3. Mechanism of Action

• In the GI tract, resin particles release their pre-bound cation (Na⁺ or Ca²⁺) and bind to target cations (e.g., K⁺) from the intestinal contents.

• This binding is a reversible ion-exchange process driven by concentration gradients and affinity for the ion.

• Bound potassium is then eliminated in the feces, lowering serum potassium levels.

---

4. Common Therapeutic Agents

Sodium Polystyrene Sulfonate (SPS)

• Exchanges sodium for potassium.

• Can be given orally or rectally (as an enema).

Calcium Polystyrene Sulfonate (CPS)

• Exchanges calcium for potassium.

• Preferred in patients who need to avoid sodium load (e.g., heart failure, severe hypertension).

Patiromer

• Non-absorbed polymer exchanging calcium for potassium.

• Slower onset; used for chronic hyperkalemia.

Sodium Zirconium Cyclosilicate (SZC)

• Inorganic cation exchanger that captures potassium in exchange for sodium and hydrogen.

• Faster onset than patiromer; can be used in both acute and chronic settings.

---

5. Pharmacokinetics and Pharmacodynamics

• Absorption: Not absorbed systemically.

• Distribution: Confined to GI lumen.

• Metabolism: Not metabolized; eliminated unchanged in feces.

• Onset:

  • SPS: gradual onset (hours).

  • Patiromer: slower onset (7–8 hours).

  • SZC: onset within 1 hour in some patients.

---

6. Clinical Indications

• Hyperkalemia:

  • Acute management (with caution for slower-acting agents).

  • Chronic control in patients at ongoing risk (CKD, heart failure, RAAS inhibitor therapy).

• Other off-label uses: occasionally in hypercalcemia or hypermagnesemia, though not common in current practice.

---

7. Contraindications

• Bowel obstruction or postoperative ileus.

• Neonates with reduced gut motility (risk of intestinal injury).

• Hypokalemia (risk of worsening deficiency).

• Known hypersensitivity to resin components.

---

8. Adverse Effects

Gastrointestinal

• Constipation, diarrhea, nausea, vomiting.

• Rare but serious: intestinal necrosis (especially with sorbitol co-administration), bowel perforation.

Electrolyte disturbances

• Hypokalemia (overtreatment).

• Hypernatremia (with sodium-based resins).

• Hypercalcemia (with calcium-based resins).

• Hypomagnesemia (with patiromer).

Other

• Edema and fluid overload (sodium-containing resins).

---

9. Drug Interactions

• May bind to other orally administered medications, reducing their absorption (e.g., levothyroxine, lithium, metformin).

• Patiromer and SZC should be given at least 3 hours before or after other oral medications (4 hours for patiromer in some recommendations).

---

10. Administration Considerations

• SPS/CPS:

  • Oral suspension in water; avoid sorbitol in high-risk patients due to intestinal injury risk.

  • Rectal administration for patients unable to take orally; retention enema preferred.

• Patiromer:

  • Powder mixed with water; taken orally.

  • Avoid heating or mixing with acidic liquids.

• SZC:

  • Powder mixed with water; taken orally; can be used with or without food.

---

11. Monitoring

• Serum potassium, sodium, calcium, and magnesium levels.

• Monitor bowel function and watch for signs of intestinal obstruction.

• Assess volume status, especially with sodium-containing resins.

---

12. Advantages and Limitations

Advantages

• Effective non-systemic method to remove excess cations.

• Can be used in patients with severe kidney dysfunction where renal elimination is impaired.

• Long-term control possible with newer agents like patiromer and SZC.

Limitations

• SPS/CPS have slow onset; not suitable as sole therapy in life-threatening acute hyperkalemia.

• Risk of serious GI side effects with older resins.

• Electrolyte shifts can cause complications if not closely monitored.