Hypercalcemia mithramycin

Mithramycin (plicamycin) is a potent cytotoxic antibiotic that inhibits osteoclast-mediated bone resorption and thereby reduces hypercalcemia. Mithramycin may be administered at a dose of 25 mcg/kg via intravenous infusion over 4 to 6 hours in saline or 5% dextrose solutions. This therapy may be repeated daily for 3 to 4 days or on alternating days for 3 to 8 doses. ° Serum calcium levels begin to fall within 12 hours of a mithramycin dose, with the peak effect generally occurring within 48 to 96 hours.Single doses are usually well tolerated. Adverse effects of mithramycin include nausea, vomiting, stomatitis, thrombocytopenia, inhibition of platelet function, and renal and hepatotoxicity. Because these adverse effects are more commonly associated with multiple doses, mithramycin is usually limited to short-term therapy in patients who have not responded to alternative therapies. Monitoring parameters include complete blood count, liver function, and renal function. Mithramycin should be avoided in patients with thrombocytopenia and liver and renal insufficiency. ... 

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. 

The answer is g. (Hardman, p 1268.) Plicamycin (mithramycin) can be used to treat hypercalcemia associated with malignancies Its mechanism of action involves inhibition of Ca reabsorption from bone, leading to a reduction in serum Ca levels. 

Mithramycin (also known as MIT and plicamy-cin) is an antibiotic that binds to DNA to regulate transcription. It attaches to specific regions of DNA that are rich in guanine and cytosine. It appears to lower serum calcium concentrations by blocking the hypercalcemic action of Vitamin D. After IV administration about 25% of the drug is excreted in the urine after 2 hours, and 40% after 15 hours. The main indications are treatment of testicular tumors and control of hypercalcemia and hypercalciuria. 

Plicamycin (mithramycin, Mithracin) is one of the chro-momycin group of antibiotics produced by Streptomyces tanashiensis. Plicamycin binds to DNA and inhibits transcription. It also inhibits resorption of bone by osteoblasts, thus lowering serum calcium levels. Very little is known about its distribution, metabolism, and excretion. Because of its severe toxicity, plicamycin has limited clinical utility. The major indication for plicamycin therapy is in the treatment of life-threatening hypercalcemia associated with malignancy. Plicamycin also can be used in the palliative therapy of metastatic testicular carcinoma when all other known active drugs have failed. 

Because of its toxicity, plicamycin (mithramycin) is not the drug of first choice for the treatment of hypercalcemia. However, when other forms of therapy fail, 25-50 mcg/kg given intravenously usually lowers serum calcium substantially within 24-48 hours. This effect can last several days. This dose can be repeated as necessary. The most dangerous toxic effect is sudden thrombocytopenia followed by hemorrhage. Hepatic and renal toxicity can also occur. Hypocalcemia, nausea, and vomiting may limit therapy. Use of this drug must be accompanied by careful monitoring of platelet counts, liver and kidney function, and serum calcium levels. 

The mechanism of action of mithramycin (Mithracin) is similar to that of dactinomycin. It is used in patients with advanced disseminated tumors of the testis and for the treatment of hypercalcemia associated with cancer. Mithramycin may cause gastrointestinal injury, bone marrow depression, hepatic and renal damage, and hemorrhagic tendency (see Chapter 62). 

Mithramycin (47) is an antitumor antibiotic isolated from Strep-tomyces plicatus. It currently is used to a limited extent for the treatment of embryonal cell carcinoma of the testes and of cancer-related hypercalcemia (85). It is reported to be a specific inhibitor of the Spl transcription factor in hematopoietic cells (86). 

Mithramycin is used as a DNA binding fluorescent dye, as an antineoplastic agent, and to reduce hypercalcemia, especially due to malignancies. Mithramycin is a potent inducer of fetal hemoglobin production in erythroid cells and is being... 

C. Other Drugs with Effects on Calcium and Bone Plicamycin (mithramycin) is an antibiotic used to reduce serum calcium and bone resorption in Paget s disease and hypercalcemia. Because of the risk of serious toxicity (eg, thrombocytopenia, hemorrhage, hepatic and renal damage), plicamycin is not used commonly and is mainly restricted to short-term treatment of serious hypercalcemia. Several diuretics can affect serum calcium levels (see this chapter s Skill Keeper). 

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