McKenna's Pharmacology for Nursing, 2e

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P A R T 2  Chemotherapeutic agents

ANTIMETABOLITES Antimetabolites (see Table 14.2) are drugs that have chemical structures similar to those of various natural metabolites that are necessary for the growth and division of rapidly growing neoplastic cells and normal cells. Antimetabolites include azacitidine ( Vidaza ), capecitabine ( Xeloda ), cladribine ( Leustatin, Litak, Movectro ), clofarabine ( Evoltra ), colaspase ( Leunase ), cytarabine (generic), fludarabine ( Farine, Fludara ), fluorouracil ( Efudix ), gemcitabine ( Gemcite, Gemzar ), mercaptopurine ( Puri-Nethol ), methotrexate ( Metho- blastin ), pemetrexed ( Alimta ), raltitrexed ( Tomudex ) and thioguanine ( Lanvis ). Therapeutic actions and indications Antimetabolites inhibit DNA production in cells that depend on certain natural metabolites to produce their DNA. They replace these needed metabolites and thereby prevent normal cellular function. Many of these agents inhibit thymidylate synthetase, DNA polymerase or folic acid reductase, all of which are needed for DNA synthesis. They are considered to be S phase specific in the cell cycle. They are most effective in rapidly dividing cells, preventing cell replication and leading to cell death (see Figure 14.5). The antimetabolites are indicated for the treatment of various leukaemias and some GI and basal cell cancers (see Table 14.2 for usual indications for each agent). Use of these drugs has been somewhat limited because neoplastic cells rapidly develop resist­ ance to these agents. For this reason, these drugs are usually administered as part of a combination therapy.

■■ BOX 14.5  Antiemetics and cancer chemotherapy (continued)

one and 8 mg dexamethasone PO on days two to four, and 32 mg ondansetron IV on day one only. • Two benzodiazepines—alprazolam ( Xanax ), 0.5 mg PO four times a day, and lorazepam ( Ativan ), 2 to 6 mg/day PO—seem to be effective in directly blocking the CTZ to relieve nausea and vomiting caused by cancer chemotherapy; they are especially effective when combined with a corticosteroid. • Haloperidol ( Haldol ), 0.5 to 2.0 mg PO four times a day, or 2 to 25 mg intramuscularly (IM) or IV, is a dopaminergic blocker that also is believed to have direct CTZ effects. • Metoclopramide ( Maxolon ), 2 mg/kg IV over at least 30 minutes, calms the activity of the GI tract; it is especially effective if combined with a corticosteroid, an antihistamine, and a centrally acting blocker such as haloperidol or lorazepam. • Prochlorperazine ( Stemetil ), 5 to 10 mg PO three to four times a day, or 5 to 10 mg IM, is a phenothiazine that has been found to have strong antiemetic action in the CNS; it can be given by a variety of routes. Nausea and vomiting are unavoidable aspects of many chemotherapeutic regimens. However, treating the person as the chemotherapy begins, using combination regimens, and providing plenty of supportive and comforting care can help to alleviate some of the distress associated with these adverse effects.

TABLE 14.2

DRUGS IN FOCUS Antimetabolites

Drug name

Dosage/route

Usual indications

azacitidine (Vidaza)

Dosage: 75 mg/m 2 per day SC for 7 days q 4 weeks

Treatment of myelodysplastic syndrome Special considerations: premedicate for nausea; monitor for bone marrow suppression; avoid pregnancy or fathering children while on drug Treatment of metastatic breast cancer with resistance to paclitaxel or anthracyclines; treatment of metastatic colorectal cancer as first-line therapy treatment of breast cancer with docetaxel in people with metastatic disease; postsurgery Dukes C colon cancer Special considerations: severe diarrhoea can occur—monitor hydration and nutrition; monitor for bone marrow suppression Treatment of active hairy cell leukaemia Special considerations: severe bone marrow depression can occur—monitor person closely and reduce dose as needed; fever is common, especially early in treatment

capecitabine (Xeloda)

2,500 mg/m 2 per day PO in two divided doses for 2 weeks, then 1 week of rest, for three cycles Dukes C colon cancer: 1250 mg/m 2 PO b.d. for 2 weeks, then 1 week of rest for a total of eight 3-week cycles

cladribine (Leustatin, Litak, Movectro)

0.09 mg/kg per day IV for 7 consecutive days