Plicamycin Mithramycin

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. 

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. 

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). 

Mithramycin A. (Aureolic acid, Plicamycin) [18378-89-7] M 1085.2, m 180-183°, [a]p° -51° (c 0.3, EtOH). Purified from CHCI3, and is soluble in MeOH, EtOH, Me2CO, EtOAc, Me2SO and H20, and moderately soluble in CHCI3, but is slightly soluble in C Hg and Et20. Fluorescent antitumour agent used in flowcytometry. [Thiem and Meyer TET 37 551 1981 NMR Yu et al. Nature 218 193 7965]. 

Plicamycin [plick a MYE sin] (mithramycin) also exerts its cytotoxicity through restriction of DNA-directed RNA synthesis. Resistance is due to P-glycoprotein efflux. Plicamycin has a relative toxic specificity for osteoclasts preventing their resorption, and lowers plasma calcium concentration in hypercalcemic patients—especially those with bone tumors. Toxicities include hemorrhage as well as effects on the bone marrow, liver, and kidneys. 

Members of the aureolic acid group include chromomycin A3 (42), olivomycin A (43) and mithramycin (plicamycin) (44). The aglycon of chromomycin A3 is identical to that of mithramycin, but differs from that of olivomycin A by a methyl group. Conversely, the sugar components for chromomycin A3 and olivomycin are nearly identical, while those in mithramycin are different (O Scheme 17). 

Synonyms Aurelic acid Aureolic acid Mithracin Mithramycin A Mitramycin Plicamycin Chemical/Pharmaceutical/Other Class Anti-neoplastic... 

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. ... 

Figure 4-20. Mithramycin (Plicamycin). The aglycone is chromomycine. The sugars are A, C, and D = olivose B = oliose, D = mycarose.

Idarubicin (Mitomycin C) Mitomycin (Mithramycin) Plicamycin (Paclitaxel)... 

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