Plicamycin

The antineoplastic antibiotics, unlike their anti-infection antibiotic relatives, do not have anti-infective (against infection) abilily. Their action is similar to the alkylating dragp. Antineoplastic antibiotics appear to interfere with DNA and RNA synthesis and therefore delay or inhibit cell division, including the reproducing ability of malignant cells. Examples of antineoplastic antibiotics include bleomycin (Blenoxane), doxorubicin (Adriamycin), and plicamycin (Mithracin). 

Plasma digoxin levels may decrease when the drug is administered with bleomycin. When bleomycin is used witii cisplatin, there is an increased risk of bleomycin toxicity Pulmonary toxicity may occur when bleomycin is administered with other antineoplastic drugs. Plicamycin, mitomycin, mitoxantrone, and dactino-mycin have an additive bone marrow depressant effect when administered with other antineoplastic drugs. In addition, mitomycin, mitoxantrone, and dactinomycin decrease antibody response to live virus vaccines. Dactinomycin potentiates or reactivates skin or gastrointestinal reactions of radiation therapy There is an increased risk of bleeding when plicamycin is administered witii aspirin, warfarin, heparin, and the NSAIDs. 

Most antineoplastic dragp have specific recommended administration techniques. For example, an infusion pump is recommended for the administration of cisplatin, and plicamycin (Mithracin) is administered by slow IV infusion during a period of 4 to 6 hours. If administration guidelines are not provided by the primary health care provider or the hospital, the nurse checks with the appropriate authorities (physician, pharmacist) regarding the administration of a specific antineoplastic drug. 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

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. 

Hypercalcemia can be treated by (1) administering 0.9% NaCl solution plus furosemide (if necessary) renal excretion (2) the osteoclast inhibitors calcitonin, plicamycin, or clodro-nate (a bisphosphonate) bone calcium mobilization i (3) the Ca +chelators EDTA sodium or sodium citrate as well as (4) glucocorticoids. 

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. 

Plicamycin (Mithracin), an inhibitor of RNA synthesis in osteoclasts, reduces serum calcium levels when infused over 4 to 6 hours every 3 to 4 days. Plicamycin s effects are slower than those of the bisphosphonates the drug is a bone marrow suppressant that can complicate clinical management if the patient is already receiving chemotherapy for the malignancy. 

In addition to these hormonal regulators, calcium and phosphate themselves, other ions such as sodium and fluoride, and a variety of drugs (bisphosphonates, plicamycin, and diuretics) also alter calcium and phosphate homeostasis. 

Plicamycin is a cytotoxic antibiotic (see Chapter 54) that has been used clinically for two disorders of bone mineral metabolism Paget s disease and hypercalcemia. The cytotoxic properties of the drug appear to involve its binding to DNA and interruption of DNA directed RNA synthesis. The reasons for its usefulness in the treatment of Paget s disease and hypercalcemia are unclear but may relate to the need for protein synthesis to sustain bone resorption. The doses required to treat Paget s disease and hypercalcemia are about one tenth the amounts required to achieve cytotoxic effects. 

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 goal of treatment is to reduce bone pain and stabilize or prevent other problems such as progressive deformity, hearing loss, high-output cardiac failure, and immobilization hypercalcemia. Calcitonin and bisphosphonates are the first-line agents for this disease. Treatment failures may respond to plicamycin. Calcitonin is administered subcutaneously or intramuscularly in doses of 50-100 MRC (Medical Research Council) units every day or every other day. Nasal inhalation at 200-400 units per day is also effective. Higher or more frequent doses have been advocated when this initial regimen is ineffective. Improvement in bone pain and reduction in serum alkaline phosphatase and urine hydroxyproline levels require weeks to months. Often a patient who responds well initially loses the response to calcitonin. This refractoriness is not correlated with the development of antibodies. 

The use of a potentially lethal cytotoxic drug such as plicamycin in a generally benign disorder such as Paget s disease is recommended only when other less toxic agents (calcitonin, alendronate) have failed and the symptoms are debilitating. Clinical data on long-term use of plicamycin are insufficient to determine its usefulness for extended therapy. However,... 

Cefamandole, cefoperazone, cefotetan, moxalactam, plicamycin, valproic acid... 

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]. 

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