How Do Calcium-Sensing Receptor Agonists Work?

Calcium-sensing receptor (CaSR) agonists are a class of drugs used to treat secondary hyperparathyroidism (SHPT-a condition in which the parathyroid glands produce a high amount of parathyroid hormone [PTH]) in patients with chronic kidney disease (gradual loss of kidney function) who are being treated with dialysis (a procedure to remove waste products and excess fluid from the blood when the kidneys stop working properly).

CaSR agonists work by decreasing PTH levels which are responsible for maintaining proper levels of both calcium and phosphorus in the body. The right amount of these substances in the body helps to prevent progressive bone disease. Increased PTH stimulates osteoclastic activity (the body's process of breaking down bone to build it up again), resulting in cortical bone resorption (remodeling of bones) and marrow fibrosis.

SHPT occurs because of other diseases that first cause low calcium levels in the body (kidney failure, severe vitamin D deficiency, and severe calcium deficiency). Over time, increased PTH levels occur and the symptoms include:

• Bone/joint pain
• Feeling weak or tired easily
• Kidney stones
• Increased frequency of urination
• Osteoporosis (thinning bones)
• Loss of appetite
• Reduced kidney function

CaSR agonists are administered intravenously (into a vein), typically three times a week at the end of each dialysis session by a doctor or a nurse at the dialysis center.

CaSR agonists work in the following ways:

• They belong to a class called "calcimimetics" (drugs that mimic the action of calcium on tissues)
• They bind to and activate the CaSR in the extracellular domain of the receptor located on the parathyroid gland, resulting in PTH reduction and suppression.
• By binding to the CaSR, they enhance the activation of the receptor by extracellular calcium, thus decreasing PTH secretion.
• They decrease the amount of PTH, calcium, and phosphorous in the body.
• The reduction in PTH is associated with a concomitant decrease in serum calcium levels.

CaSR agonists are used to treat SHPT (overactivity of the parathyroid glands occurs in response to another medical condition that causes calcium loss) for patients with chronic kidney disease on hemodialysis.

Some of the common side effects include:

• Diarrhea
• Nausea
• Vomiting
• Headache
• Myalgia (muscle pain)

Other rare side effects include:

• Dizziness (feeling faint, weak, or unsteady)
• Seizures (a sudden, uncontrolled electrical disturbance in the brain)
• Numb/tingling skin
• Severe muscle spasms
• Swelling of the face
• Hypocalcemia (low blood calcium level)
• Hypophosphatemia (low level of phosphate in the blood)
• Unusual tiredness

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of CaSR agonists include:

• Etecalcetide
• Parsabiv