McKenna's Pharmacology for Nursing, 2e

198

P A R T 2  Chemotherapeutic agents

Clinically important drug–drug interactions Alkylating agents that are known to cause hepatic or renal toxicity should be used cautiously with any other drugs that have similar effects. In addition, drugs that are toxic to the liver may adversely affect drugs that are metabolised in the liver or that act in the liver (e.g. oral anticoagulants). Always check for specific drug–drug interactions for each agent in a drug guide. Prototype summary: Chlorambucil Indications: Palliative treatment of chronic lymphocytic leukaemia, malignant lymphomas and Hodgkin’s disease. Actions: Alkylates cellular DNA, interfering with the replication of susceptible cells. Pharmacokinetics: Route Onset Peak Duration Oral Varies 1 hour 15–20 hours T 1/2 : 60 to 90 minutes, metabolised in the liver and excreted in the urine. Adverse effects: Tremors, muscle twitching, confusion, nausea, hepatotoxicity, bone marrow suppression, sterility, cancer. of allergy to any of the alkylating agents to avoid hypersensitivity reactions ; bone marrow suppression to prevent further suppression ; renal or hepatic dysfunction that might interfere with drug metabolism and excretion ; and current status related to pregnancy or breastfeeding to prevent potentially serious adverse effects on the fetus or breastfeeding baby . ■ ■ Perform a physical assessment to establish baseline data for determining the effectiveness of the drug and the occurrence of any adverse effects associated with drug therapy . ■ ■ Assess orientation and reflexes to evaluate any central nervous system (CNS) effects ; respiratory rate and adventitious sounds to monitor the disease and to evaluate for respiratory or hypersensitivity effects ; pulse, rhythm and auscultation to monitor for systemic or cardiovascular effects; and bowel sounds and mucous membrane status to monitor for GI effects . Care considerations for people receiving alkylating agents Assessment: History and examination ■ ■ Assess for contraindications or cautions: history

GI effects include nausea, vomiting, anorexia, diarrhoea and mucous membrane deterioration, all of which are related to the drugs’ effects on the rapidly multiplying cells of the GI tract. Hepatic toxicity and renal toxicity may occur, depending on the exact mechanism of action. Alopecia , or hair loss, related to effects on the hair follicles, may also occur. All drugs that cause cell death can cause a potentially toxic increase in uric acid levels. In 2006, a new drug, rasburicase , was introduced to manage uric acid levels in children (see Box 14.4). Amifostine ( Ethyol ) is a cytoprotective (cell-protecting) drug that preserves healthy cells from the toxic effects of cisplatin. It is thought to react to the specific acidity and vascularity of non-tumour cells to protect them, and it may also act as a scavenger of free radicals released by cells that have been exposed to cisplatin. Amifostine is given at a dose of 910 mg/m 2 four times a day as a 15-minute IV infusion starting within 30 minutes after starting cisplatin therapy; timing is very important to its effectiveness. Now approved for use to prevent the renal toxicity associated with the use of cisplatin in individuals with advanced ovarian cancer, amifostine is under investigation as an agent for protecting lung fibroblasts from the effects of paclitaxel. Because amifostine is associated with severe nausea and vomiting, concurrent administration of an antiemetic is recommended. It also can cause hypotension and individuals should be monitored closely for this condition. Mesna ( Uromitexan ) is a cytoprotective agent that is used to reduce the incidence of haemorrhagic cystitis caused by ifosfamide or cyclophosphamide. Mesna, which is known to react chemically with urotoxic metabolites of ifosfamide, is given intravenously at the time of the ifosfamide injection at a dose that is 20% of the ifosfamide dose and is repeated 4 and 8 hours afterwards. Because mesna has been associated with nausea and vomiting, an antiemetic may be useful. ■■ BOX 14.3  Drugs that protect cells from alkylating agents Rasburicase ( Fasturtec ) was approved in 2006 for the management of plasma uric acid levels in children with leukaemia, lymphoma and solid tumour malignancies who are receiving antineoplastic therapy associated with tumour lysis and subsequent elevated serum uric acid levels. It is administered as a single daily IV infusion of 0.15 to 0.2 mg/kg over 30 minutes for 5 days. Chemotherapy should be started 4 to 24 hours after the first dose of rasburicase. Uric acid levels should be monitored frequently, using prechilled, heparinised vials that are kept in an ice-water bath. This analysis should be done within 4 hours of each rasburicase dose. ■■ BOX 14.4  Drug to manage rising uric acid levels associated with tumour lysis