Hyperparathyroidism cinacalcet

Block GA, Martin KJ, de Francisco AL et al (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350 1516-1525... 

Paricalcitol is a synthetically manufactured analogue of calcitriol. It is indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease. Cinacalcet, a drug that acts as a calcimimetic, can be added if the effects on PTH levels are isufficient. 

Cinacalcet is the first representative of a new class of drugs that activates the calcium sensing receptor (CaR). CaR is widely distributed but has its greatest concentration in the parathyroid gland. Cinacalcet blocks PTH secretion by this mechanism and is approved for the treatment of secondary hyperparathyroidism in chronic kidney disease and for the treatment of parathyroid carcinoma. 

This rather common disease, if associated with symptoms and significant hypercalcemia, is best treated surgically. Oral phosphate and bisphosphonates have been tried but cannot be recommended. Asymptomatic patients with mild disease often do not get worse and may be left untreated. The calcimimetic agent cinacalcet, discussed previously, has been approved for secondary hyperparathyroidism and is in clinical trials for the treatment of primary hyperparathyroidism. If such drugs prove efficacious, medical management of this disease will need to be reconsidered. 

Cinacalcet Activates the calcium sensing receptor Inhibits PTH secretion Hyperparathyroidism Nausea... 

Quarles LD Cinacalcet HCI A novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease. Kidney Int Suppl 2005 Jul(96) S24. 

Cinacalcet (Sensipar) [Hyperparathyroidism Agent/ Calcimimetic] Uses Secondary hyperparathyroidism in CRF T Ca2+ in parathyroid carcinoma Action 4- PTH by T Ca-sensing receptor sensitivity Dose ... 

Blizzard, RM, Chee, D and Davis, W, 1966, The incidence of parathyroid and other antibodies in the sera of patients with idiopathic hypoparathyroidism, Clin Exp Immunol 1 119-128 Block, GA, Martin, KJ, de Francisco, AL, Turner, SA, Avram, MM, Suranyi, MG, Hercz, G, Cunningham, J, Abu-Alfa, AK, Messa, P, Coyne, DW, Locatelli, F, Cohen, RM, Evenepoel, P, Moe, SM, Fournier, A, Braun, J, McCary, LC, Zani, VJ, Olson, KA, Drueke, TB and Goodman, WG, 2004, Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis, N Engl J Med 350 1516-1525... 

Dong BJ. Cinacalcet An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 27 1725-1751. 

The potential application of this catalytic system in industry lies in the synthesis of (R) a (1 naphthyl)ethylamine (50), a key precursor to Cinacalcet hydrochloride (51) for the treatment of hyperparathyroidism and hypercalcemia, via the hydrogenation of a (1 naphthyl)enamide at a decreased catalyst loading (0.1 mol%) in TFE under 80 bar of H2 within 24h (Scheme 9.12) [53]. 

A review of the use of cinacalcet HCl for secondary hyperparathyroidism is provided in Chap. 44. Cinacalcet HCl is administered at a starting dose of 30 mg given orally twice daily for the treatment of parathyroid carcinoma. The dosage is titrated every 2 to 4 weeks in 30-mg increments twice daily. The maximum approved dosage is 90 mg three to four times daily. 

Cinacalcet is a calcimimetic agent that lowers parathyroid hormone (PTH) levels by increasing sensing receptor to extracellular calcium. This drug is indicated in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and hypercalcemia in patients with parathyroid carcinoma. 

Cinacalcet is available in 30-, 60-, and 90-mg tablets. Optimal doses have not been defined. The recommended starting dose for treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis is 30 mg once daily, with a maximum of 180 mg/day. For treatment of parathyroid carcinoma, a starting dose of 30 mg twice daily is recommended, with a maximum of 90 mg four times daily. The starting dose is titrated upward every 2 to 4 weeks to maintain the PTH level between 150 and 300 pg/mL (secondary hyperparathyroidism) or to normalize serum calcium (parathyroid carcinoma). The principal adverse event with cinacalcet is hypocalcemia. Thus, the drug should not be used if the initial serum calcium concentration is less than 8.4 mg/dL serum calcium and phosphorus concentrations should be measured within 1 week, and PTH should be measured within 4 weeks after initiating therapy or after changing dosage. 

Calcimimetics mimic the action of calcium via the CaSR to inhibit PTH secretion by the parathyroid glands. Because of this enhanced sensitivity, they decrease PTH secretion for any given level of Ca. The calcimimetic cinacalcet (sensipar) is FDA-approved for the treatment of secondary hyperparathyroidism due to chronic renal disease and for patients with hypercalcemia associated with parathyroid carcinoma (Figure 61-9). In clinical trials, cinacalcet also effectively reduced PTH levels in patients with primary hyperparathyroidism and normalized serum calcium without altering bone mineral density for up to 2 years. 

The principal adverse effect of cinacalcet is hypocalcemia. The drug should not be used if the initial serum calcium is <8.4 mg/dL serum calcium and phosphate concentrations should be measured within one week and PTH should be measured within 4 weeks of therapy initiation. Adynamic bone disease may develop in patients with secondary hyperparathyroidism, so the drug should be discontinued or the dose decreased if the PTH level falls below 150 pg/mL. 

In six cases of hthium-associated hyperparathyroidism, four had parathyroid adenomas [67, 68 ]. The authors suggested that lithium can help uncover pre-existing parathyroid disease, although there does appear to be an increased incidence of multiglandular or multiadenomatous disease in patients taking lithium. Surgical treatment is often curative when adenomas are discovered. When hypercalcemia persists, cinacalcet, a calcimimetic can be used effectively. 

Franceschini N, Joy MS, Kshirsagar A. Cinacalcet HCl a calcimimetic agent fort he management of primary and secondary hyperparathyroidism. Expert Opin. Invest. Drugs 2003 12(8) 1413-1421. 

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