Download Chapter 20 - Antineoplatic Drugs - Delmar

Fundamentals of Pharmacology
for Veterinary Technicians
Chapter 20
Antineoplastic and
Immunosuppressive Drugs
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Basic Terminology
• Anticancer drugs stop the cancerous activity of
malignant cells
– Also called antineoplastic agents and chemotherapeutic
agents
• Characteristics of malignant cells include rapid
cell division and growth, different rates of cellular
drug uptake, and increased cellular response to
selected anticancer drugs
• Some factors present in malignant cells are also
found in normal cells
– Rapid cell division and growth occur in cells of the GI
tract, bone marrow, reproductive organs, and hair
follicles
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Cell Cycle Phases
• The five phases of
the cell cycle:
Insert Figure 20-1
– G1: enzymes
needed for DNA
synthesis are
produced
– S: DNA synthesis
and replication
– G2: RNA and
protein synthesis
– M: mitosis phase
– G0: resting phase
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Definitions Related to
Antineoplastic Agents
• Growth fraction: percentage of
cancer cells that are actively dividing
– A high growth fraction occurs when
cells are dividing rapidly
– When tumors age and enlarge, their
growth fraction decreases
• Doubling time: time required for the
number of cancer cells to double
– When tumors age and enlarge, their
doubling time increases
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Administering Antineoplastic
Agents
• Antineoplastic agents are often administered in
various protocols known as combination therapy
• Calculation of antineoplastic drug doses is based
on body surface area in square meters
• When administering antineoplastic agents, great
care must be taken; refer to Table 20-2
• When administering antineoplastic agents IV,
infuse unmedicated IV solution before and after
administration of the drug to ensure that
antineoplastic drug residues do not remain on the
equipment
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Antineoplastic Agents
• Cell-cycle nonspecific (CCNS):
– Alkylating agents cross-link DNA to
inhibits its replication
• Examples include cyclophosphamide,
cisplatin, chlorambucil, melphalan, and
carboplatin
– Antitumor antibiotics inhibit DNA, RNA,
and protein synthesis
• Examples include doxorubicin,
dactinomycin, and mitoxantrone
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Antineoplastic Agents
• Cell-cycle nonspecific (CCNS)
(cont.):
– Steroid drugs have anti-inflammatory
effects, suppress bone marrow cells,
reduce edema, and suppress tumor
growth
• Examples include corticosteroids,
estrogens, progestins, and androgens
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Antineoplastic Agents
• Cell-cycle specific (CCS):
– Antimetabolites affect the S phase
involving DNA synthesis
• Examples include methotrexate, 5fluorouracil, cytarabine, and azathioprine
– Alkaloids stop cancer cell division
• Examples include vincristine and
vinblastine
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Antineoplastic Agents
• Biologic response modifiers (BRMs): used
to enhance the body’s immune system;
used in conjunction with antineoplastic
protocols
– Interferons are a group of proteins that have
antitumor and antiviral effects; used to treat
tumors and viral infections in cats
• There are three types of interferon: alpha, beta, and
gamma
– Colony stimulating factors (CSFs) stimulate
the growth, maturation, and differentiation of
bone marrow stem cells; have been used to
treat neutropenia in dogs and cats
• An example is filgrastim
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Antineoplastic Agents
• Biologic response modifiers (BRMs)
(cont.):
– Interleukins are a group of chemicals that play
various roles in the immune system and
promote the replication of antigen-specific T
cells
– Acemannan is a potent stimulator of
macrophage activity and is used to treat
fibrosarcomas and mast cells in dogs and cats
– Monoclonal antibodies have cytotoxic effects
on tumor cells and are used in conjunction
with other antineoplastic agents
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Antineoplastic Agents
• Immunosuppressive drugs work by interfering
with one of the stages of the cell cycle or by
affecting cell messengers
– Cyclosporine inhibits the proliferation of Tlymphocytes; used for managing KCS in dogs and
immune-mediated skin disorders
– Azathioprine affects cells in the S phase of the cell
cycle and also inhibits T- and B-lymphocytes; used
mainly in dogs for immune-mediated disease
– Cyclophosphamide interferes with DNA and RNA
replication, disrupting nucleic acid function; has
been used for immune-mediated diseases
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Antineoplastic Agents
• Enzymes
– L-asparaginase is an example of an enzyme
used in the treatment of cancer
– L-asparaginase works by hydrolyzing
asparagines into aspartic acid and ammonia
– Cancer cells need an exogenous source of
asparagine for survival; normal cell can
synthesize asparagine
– Side effects of L-asparaginase include pain at
the injection site, hypotension, and diarrhea
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Adverse Reactions to
Antineoplastic Agents
• Antineoplastic agents can cause
adverse reactions in rapidly dividing
normal cells
• Some of these adverse reactions are
listed in Table 20-3
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.