Calcimimetics are a class of medications designed to mimic the effect of calcium on tissues by activating specific receptors that respond to calcium. They are not supplements that increase the body’s calcium supply, but compounds that trick the body into responding as if calcium levels were higher than they are. This action addresses hormonal imbalances related to mineral metabolism and provides a targeted approach for managing conditions where calcium-sensing mechanisms are dysregulated.
Mechanism of Action
The primary function of calcimimetics centers on their interaction with the calcium-sensing receptor (CaSR). The CaSR is a protein located on the surface of cells in the parathyroid glands, four small glands in the neck that regulate calcium. These receptors constantly monitor the amount of calcium in the bloodstream. When calcium levels are appropriate, the CaSR signals the parathyroid glands to moderate their activity.
Calcimimetic drugs bind to the CaSR at a site distinct from where calcium itself binds, a process known as allosteric activation. This binding action makes the receptor more sensitive to the calcium already circulating in the blood. The drug amplifies the signal from existing calcium, fooling the parathyroid gland into perceiving that calcium levels are elevated. This is analogous to increasing a thermostat’s sensitivity, making it react to smaller changes in temperature.
This enhanced sensitivity triggers a response from the parathyroid gland. Believing that blood calcium is high, the gland reduces its production and secretion of parathyroid hormone (PTH). The reduction of PTH is the therapeutic goal, as this hormone drives the release of calcium from bones into the blood. By suppressing PTH, calcimimetics lower blood calcium levels and prevent excessive bone turnover.
Conditions Treated with Calcimimetics
The most widespread use of calcimimetics is managing secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) who require dialysis. In advanced kidney disease, the body’s ability to excrete phosphorus and produce active vitamin D is impaired. This leads to low blood calcium and high phosphorus levels, which continuously stimulate the parathyroid glands to produce excessive PTH. This overactivity, or SHPT, can lead to severe bone disease.
Calcimimetics counteract this process by reducing PTH levels, helping to control the body’s calcium and phosphorus balance. For patients on dialysis, these medications can decrease the need for surgical removal of the parathyroid glands (parathyroidectomy). By normalizing PTH, calcimimetics help prevent progressive bone disorders associated with mineral metabolism in CKD.
Beyond their primary use for SHPT, calcimimetics are also employed in less common situations. One such use is treating hypercalcemia, or dangerously high levels of calcium in the blood, in patients with parathyroid carcinoma. This is a rare cancer of the parathyroid glands that leads to uncontrolled PTH secretion. These drugs may also be an option for patients with primary hyperparathyroidism when surgery to remove the gland is not a viable option.
Common Side Effects and Monitoring
A primary risk of calcimimetics is developing hypocalcemia, or abnormally low blood calcium levels. This occurs because the drugs are effective at suppressing PTH, the body’s main defense against low calcium. Other side effects include gastrointestinal issues such as nausea and vomiting. Muscle spasms can also occur, often related to the drop in blood calcium.
Given these potential effects, patient monitoring is a standard part of treatment. Individuals prescribed calcimimetics undergo regular blood tests to check their serum calcium, phosphorus, and PTH levels. This monitoring allows healthcare providers to ensure the medication is working effectively without causing severe hypocalcemia.
The results of these blood tests guide dosage adjustments to find a balance that controls hyperparathyroidism while maintaining safe calcium levels. For instance, if PTH levels remain too high, the dose may be increased. Conversely, if calcium levels fall too low, the dose will be reduced or temporarily stopped.
Administration and Specific Medications
Calcimimetics are available in oral or intravenous formulations. The most well-known oral medication is cinacalcet, sold under brand names like Sensipar. Patients take cinacalcet as a tablet once a day with food.
For patients undergoing hemodialysis, an intravenous option called etelcalcetide (Parsabiv) is available. This medication is administered by a healthcare professional at the end of each dialysis session, usually three times a week. This method ensures adherence, as the drug is given in a controlled clinical setting.
Treatment with either medication begins at a low dose. The dosage is then gradually increased over several weeks based on the patient’s response, which is determined through regular blood tests. This titration process allows clinicians to tailor the treatment to the individual’s specific needs.