Cinacalcet: Application, Mechanism of action and Side effects

What is Cinacalcet?

Cinacalcet is an orthosteric modulator of the calcium-sensitive receptor (CaSR) and acts as a calcimimetic. It increases the sensitivity of calcium-sensitive receptors to extracellular calcium, resulting in lower serum calcium levels. It is indicated for the treatment of secondary hyperparathyroidism (dialysis population), primary hyperparathyroidism (patients may not be candidates for surgical treatment) and for the prevention of calcification in the treatment of patients with end-stage renal disease or dialysis. It may also be a potential treatment for hypercalcaemia in patients with parathyroid cancer.

Cinacalcet is a medication that treats chronic kidney disease (dialysis) and high levels of calcium in your blood if you have parathyroid gland conditions. This medication comes in a tablet form that you can take by mouth with a glass of water. The brand name of this drug is Sensipar®.

Mechanism of action

Cinacalcet is a “calcimimetic,” meaning that it acts on the calcium-sensing receptors (CaSR) located on the chief cells of the parathyroid gland. CaSR detects a minor change in the extracellular calcium level and maintains the PTH level accordingly. This process occurs through PTH gene transcription and parathyroid cell growth. The CaSR couples with a 7-transmembrane domain G-proteins. On the chief cells, the predominant forms are Gi and Gq. Once activated, cAMP accumulation becomes inhibited, and simultaneously the phosphoinositide-phospholipase C pathway gets stimulated. The ensuing increase in IP3 and DAG levels leads to intracellular calcium influx. The end result of this the Gq pathway is specifically dominant-negative, i.e., suppression of PTH secretion. Disruption of this cascade has also been present in various etiologies of hyperparathyroidism.

“Calcimimetic” medications, as the name suggests, may not be the real calcium ligands, but they activate these receptors and utilize the Gq/Gi pathways to establish the negative feedback loop to raise calcium levels. This feedback occurs through the suppression of both the production of PTH and its secretion and ultimately leads to the mitigation of calcium and phosphorus products in the blood.

Dosing

The dosage of the drug is closely related to the patient's age, physical condition, degree of illness, etc. Generally, please follow the doctor's instructions.

For oral dosage form (tablets):

For hypercalcemia with parathyroid cancer or hyperparathyroidism: Adults—At first, 30 milligrams (mg) two times a day. Your doctor may adjust your dose every 2 to 4 weeks. Children—Use and dose must be determined by your doctor.

For hyperparathyroidism with chronic kidney disease: Adults—At first, 30 milligrams (mg) once a day. Your doctor may adjust your dose every 2 to 4 weeks. Children—Use and dose must be determined by your doctor.

Side effects

The common side effects are nausea and vomiting. It can occur in up to one-third of patients taking this medication. Dizziness, diarrhea, and decreased appetite are other side effects of this medication as well. Cinacalcet can cause hypocalcemia. The patients on this medication need to be closely followed for common symptoms associated with hypocalcemia include tingling, muscle twitching, cramps, changes in mood, or irritability. On the ECG, a prolonged QT interval may be present. Patients with a history of congenital long QT syndrome, family history of long QT syndrome, and other conditions that predispose patients to QT interval prolongation may be at increased risk. Oversuppresion of PTH can cause adynamic bone disease.  

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