Calcitonin administration

Chung SY, Chen TH, Lai SL, Huang CH, Chen WH. Hypercalcaemia and status epilepticus relates to salmon calcitonin administration in breast cancer. Breast 2005 14(5) 399 102. 

To improve the absorption of peptides and proteins, the employment of different enzymatic inhibitors has been suggested. For example, some authors have demonstrated the usefulness of inhibitors of both exo- and endopeptidases to promote calcitonin absorption across rat vaginal mucosa [93]. A direct relationship was found between the effect of peptidase inhibitors of in vitro degradation constant of calcitonin in vaginal mucosa homogenates and in vivo promotion of drug absorption, indicated by the decrease in plasma calcium levels after calcitonin administration in rats. The peptidase inhibitors tested were pepstatin, bestatin, and leupeptin. 

The principal effects of calcitonin are to lower serum calcium and phosphate by actions on bone and kidney. Calcitonin inhibits osteoclastic bone resorption. Although bone formation is not impaired at first after calcitonin administration, with time both formation and resorption of bone are reduced. Thus, the early hope that calcitonin would prove useful in restoring bone mass has not been realized. In the kidney, calcitonin reduces both calcium and phosphate reabsorption as well as reabsorption of other ions, including sodium, potassium, and magnesium. Tissues other than bone... 

The answer is c. (Hardman, p 15230 Administration of intravenous CaG would immediately correct the tetany that might occur in a patient in whom a thyroidectomy was recently performed. Parathyroid hormone would act more slowly but could be given for its future stabilizing effect. Long-term control of a patient after a thyroidectomy can be obtained with vitamin D and dietary therapy Calcitonin is a hypocalcemic antagonist of parathyroid hormone. Plicamycin (mithramycin) is used to treat Paget s disease and hypercalcemia. The dose employed is about one-tenth the amount used for plicamycin s cytotoxic action. 

Bonucci, E., Ballanti, P., Ramires, P.A., Richardson, J.L., and Benedetti, L.M., Prevention of ovariectomy osteopenia in rats after vaginal administration of Hyaff 11 microspheres containing salmon calcitonin, Calcif. Tissue Int., 56 274-279 (1995). 

Three forms of calcitonin are available, salmon, porcine and human calcitonin. Long-term use of porcine calcitonin, being the most antigenic product, can lead to the production of neutralizing antibodies. Synthetic salmon preparations are therefore preferable. Human calcitonin is less immunogenic but it is also less active. Human calcitonin monomer has a half-life of about 10 minutes while the half-life of salmon calcitonin is considerably longer. However these half-lives are not directly related to the duration of action which varies from 30 min to 12 hours after intravenous administration and from 8 hours to 24 hours when administered subcutaneously or intramuscularly. Calcitonin is metabolized in the blood and in tissues like for example the kidneys. 

Alternatives to steroid hormone therapy for osteoporosis include raloxifene, bisphosphonates, sodium fluoride, vitamin D and calcium supplementation, calcitonin, and parathyroid hormone. Tamoxifen has estrogenic effects on bone and delays bone loss in postmenopausal women. However as a result of estrogenic activity in the uterus, long-term tamoxifen administration has been associated with an increased risk of... 

Calcitonin is also effective in reducing serum calcium levels in life-threatening hypercalcemia however, it is not as rapid or as effective as the bisphosphonates. Subcutaneous administration of salmon (Calcimar) or human (Cibacalcin) calcitonin reduces serum calcium levels within 3 to 5 days in 75 to 90% of malignant hypercalcemias. 

Calcitonin (Miacalcin, Miacalcin Nasal Spray) is a synthetic 32-amino acid polypeptide that is identical to salmon calcitonin. Salmon calcitonin is more potent than human calcitonin because of its higher affinity for the human calcitonin receptor and its slower metabolic clearance. Administration is by subcutaneous or intramuscular injection or by nasal spray. The absorption of the nasal form is slower than that of the parenteral routes. 

With the exception of the possible development of a hypervitaminosis associated with high-dose administration of vitamin D2 or D3, the compounds discussed in this chapter are relatively safe. Allergic reactions to the injection of calcitonin and PTH have occurred and chronic use of some bisphosphonates has been associated with the development of osteomalacia. The principal side effects of intravenous bisphosphonates are mild and include low-grade fever and transient increases in serum creatinine and phosphate levels. Oral bisphosphonates are poorly absorbed and can cause esophageal and gastric ulceration. They should be taken on an empty stomach the individual must remain upright for 30 minutes after ingestion. 

Nasal absorption. Sucrose ester of coconut fatty acid in aqueous ethanol solution (sucrose cocoate SL-40) administered intrana-sally to anesthetized male Sprague-Dawley rats at a dose of 0.5% sucrose cocoate with insulin, produced a rapid and significant increase in plasma insulin level with a concomitant decrease in blood glucose levels. Administration of a dose of 0.5% sucrose cocoate with calcitonin produced a rapid increase in plasma calcitonin levels and a concomitant decrease in plasma calcium levels . 

Calcium play vital role in excitation - contraction coupling in myocardium. Calcium mediates contraction in vascular and other smooth muscles. Calcium is required for exocytosis and also involved in neurotransmitters release. Calcium also help in maintaining integrity of mucosal membranes and mediating cell adhesions. Hypercalcemia may occur in hyperthyroidism, vitamin D intoxication and renal insufficiency, which can be treated by administration of calcitonin, edetate sodium, oral phosphate etc. Hypocalcemia may occur in hypothyroidism, malabsorption, osteomalacia secondary to leak of vitamin D or vitamin D resistance, pancreatitis and renal failure. Hypocalcemia can be treated by chloride, gluconate, gluceptate, lactate and carbonate salts of calcium. 

Calcitonin has proved useful as ancillary treatment in a large number of patients. Calcitonin by itself seldom restores serum calcium to normal, and refractoriness frequently develops. However, its lack of toxicity permits frequent administration at high doses (200 MRC units or more). An effect on serum calcium is observed within 4-6 hours and lasts for 6-10 hours. Calcimar (salmon calcitonin) is available for parenteral and nasal administration. 

Kuraishi, Y., Nanayama, T., Ohno, H., Minami M., Satoh M. Antinocieption induced in rats by intrathecal administration of antiserum against calcitonin gene-related peptide, Neurosci. Lett. 1988, 92, 325-329. 

Flushing occurs soon after administration of calcitonin in up to 20% of patients and usually settles within several minutes (10). 

A 60-year-old woman tolerated daily intranasal calcitonin for 6 months of the year for 4 years (19). She developed nasal watering, nasal and ocular pruritus, and sweating immediately after the administration of nasal calcitonin when she restarted after a 6-month break. These symptoms recurred 2 years later, with abdominal pain and hypotension, after 10 months of... 

Yamamoto, A., et al. 2001. Absorption of water soluble compounds with different molecular weights and [ASU1.7]-eel calcitonin from various mucosal administration sites. J Control Release 76 363. 

Santi, P., et al. 1997. Transdermal iontophoresis of salmon calcitonin can reproduce the hypocal-cemic effect of intravenous administration. Farmaco 52 (6) 445. 

Nakamura, K., et al. 2003. Transdermal administration of salmon calcitonin by pulse depolarization-iontophoresis in rats. Int J Pharm 218 93. 

Ahsan, F., et al. 2001. Enhanced bioavailability of calcitonin formulated with alkylglycosides following nasal and ocular administration in rats. Pharm Res 18 1742. 

Kaskani E, Lyritis GP, Kosmidis C, et al. Effect of intermittent administration of 200 IU intranasal salmon calcitonin and low doses of 1 alpha(OH) vitamin D3 on bone mineral density of the lumbar spine and hip region and biochemical bone markers in women with postmenopausal osteoporosis a pilot study. Clin Rheumatol. 2005 24 232-238. 

Takeuchi, H., Matsui, Y., Yamamoto, H., and Kawashima, Y. Mucoadhesive properties of carbopol or chitosan-coated liposomes and their effectiveness in the oral administration of calcitonin to rats. J. Contr. Rel. 86 235—242, 2003. 

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