McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 4  Antineoplastic agents

1,000,000-cell tumour

10,000-cell tumour

1000-cell tumour

100-cell tumour

10-cell tumour

1-cell tumour

1st course of chemotherapy

2nd course of chemotherapy

3rd course of chemotherapy

4th course of chemotherapy

5th course of chemotherapy

FIGURE 14.3  Cell kill theory. A set percentage of cells is killed after each dose of chemotherapy. The percentage killed is dependent upon the drug therapy. In this example, each course of chemotherapy kills 90% of cells in a cancerous tumour. After the fifth course of chemotherapy in this example, a 1-cell tumour remains; the person’s immune system would destroy this malignant cell.

used today include alkylating agents, antimetabolites, antineoplastic antibiotics, mitotic inhibitors, hormones and hormone modulators, cancer cell-specific agents, protein tyrosine kinase inhibitors (which target enzymes specific to the cancer cells) and a group of antineoplastic agents that cannot be classified elsewhere. Other drugs are used to combat the serious adverse effects that can be associated with the antineoplastic drugs. These drugs are used as adjunctive therapy. Figure 14.4 shows sites

of action of these drugs. Box 14.1 discusses use of these drugs across the lifespan. As discussed in Chapter 7, all cells progress through a cell cycle. Different types of cells progress at different rates (see Figure 7.6). Rapidly multiplying cells, or cells that replace themselves quickly, include those lining the gastrointestinal (GI) tract and those in hair follicles, skin and bone marrow. These cells complete the cell cycle every few days. Cells that proceed very slowly through

Cilia with microtubules

erlontinib gefitnib imatinib bortezomib lapatinib nilotinib sorafenib sunitinib temsirolimus

Golgi apparatus

Peroxisomes Lysosomes

Cell membrane

docetaxel paclitaxel

Polyribosomes

Nucleus: Nuclear membrane Nuclear pore Nucleolus cladribine hydroxyurea irinotecan procarbazine

Centrioles

Microtubules

FIGURE 14.4  Sites of action of non–cell cycle-specific antineoplastic agents. Alkylating agents interfere with RNA, DNA or other cellular proteins. For example, procarbazine blocks DNA, RNA and protein synthesis. Hormone modulators react with specific receptor sites to block cell growth and activity. Mitotic inhibitors such as docetaxel and paclitaxel inhibit microtubular reorganisation. The antimetabolite cladribine and miscellaneous agent hydroxyurea block DNA synthesis. The miscellaneous agent irinotecan disrupts DNA strands. Cell-specific agents such as gefitinib, erlotinib, lapatinib, nilotinib, sorafenib, sunitinib, temsirolimus and imatinib inhibit protein tyrosine kinases. Bortezomib is a proteasome inhibitor.

Hormone modulators

Smooth endoplasmic reticulum

Mitochondria

Alkylating agents

Rough endoplasmic reticulum

Mechanism of action unknown tretinoin—promotes cell differentiation Mechanism of action unknown tr tinoi —pr motes cell differentiation