Cell Cycle and Mitosis Phases

• The four major phases of the cell cycle are G1, S, G2, and Mitosis.
• The resting phase with no cellular division is G0.

Mitosis Phases

• Prophase involves chromatin condensing into distinct chromosomes, migrating to the cell center. The nuclear envelope breaks down, and spindle fibers form.
• Metaphase is characterized by the disappearance of the nuclear membrane, development of the spindle, and alignment of chromosomes.
• Anaphase entails the separation of paired chromosomes (sister chromatids) and the lengthening of spindle fibers.
• Telophase sees chromosomes sectioned off into two distinct new nuclei with equal genetic content, with cytokinesis (division of the cytoplasm) beginning after anaphase and finishing after telophase to form two new cells.
• Malignant cells escape normal mechanisms controlling cellular division and growth
• Metastasis is the migration and invasion of malignant cells into other tissues
• P53 is an important tumor suppressor

DNA and Chemotherapy

• Telomeres are the DNA "end caps" linked to cellular aging.
• Chemotherapy toxicity side effects often relate to rapidly dividing cell targets like hair follicles and mucosal cells
• Aseptic methods and prophylactic antibiotics are anesthetic considerations for immunosuppressed cancer patients

Alkylating Agents

• Work is not done in any specific cell-cycle phase
• Pulmonary side effects include pneumonitis, fibrosis, and decreased diffusion capacity
• They inhibit the activity of plasma cholinesterase, affecting anesthetic drugs
• Cardiotoxicity is an additional side effect
• Cyclophosphamide is a specific example

Platinum Complexes

• Affect solid tumors and are not cell-cycle specific
• They cross-link DNA, disrupting its replication and division in an alkylating-like effect
• Cisplatin side effects resemble those of loop diuretics and aminoglycosides: nephrotoxicity and ototoxicity
• Other side effects include peripheral neuropathy, nausea and vomiting, myelosuppression, and hypersensitivity reactions

Antimetabolites

• These mimic cellular nutrients like folic acid and inhibit enzymes like nucleobases, working primarily in the S phase
• Dermatologic side effects include dermatitis, pigmentation changes, nail changes, alopecia, and photosensitivity

Other Toxicities

• Significant GI toxicity (stomatitis, ulceration, diarrhea, hemorrhagic enteritis, perforation) is a notable side effect along with nephrotoxicity, hepatotoxicity, and CNS effects

Topoisomerase Inhibitors

• Inhibit topoisomerase enzymes during the S and early G2 phases, leading to DNA breakage
• Cardiotoxicity is a heart condition commonly caused by antitumor antibiotics like daunorubicin
• Free radicals disrupt cardiac proteins and cell membrane components, causing cardiotoxicity

Bleomycin

• Causes pulmonary toxicity
• Anesthetic considerations minimize crystalloids, consider colloids, and keep FiO2 low (below 30% if possible)
• Excessive crystalloid administration and hyperoxia during anesthesia increase the risk of pulmonary toxicity

Microtubule Inhibitors

• Are active in the M phase
• Two main drug classes: Vinca Alkaloids and Taxanes
• Neuromuscular side effects include sensory-motor neuropathy, areflexia, paresthesia’s, skeletal weakness, skeletal muscle pain, and ataxia.
• Dexamethasone is provided for edema and effusion, and Sigamedex is given instead of Neostigmine for residual musculoskeletal blockade
• Regional anesthesia may worsen neuropathy

Signal Transduction Modifiers

• Disrupt growth factor-receptor interactions or target overexpressed antigens
• Monoclonal antibodies target autoimmune diseases and cancer antigens or receptors.
• Monoclonal antibodies also treat multiple sclerosis and rheumatoid arthritis
• Anti-estrogens like Tamoxifen can increase the risk of thromboembolic events and stroke (boxed warning)
• Vaccines are administered in cancer or at-risk populations to decrease the risk of developing cancer

Memory Master Points

• Bleomycin is toxic to the pulmonary organ, causing endothelial and epithelial damage via free radical production in the presence of oxygen and iron/copper, leading to pulmonary fibrosis
• O2 concentration for patients taking bleomycin should be above 90 but below 100 (lower inhaled oxygen concentrations below 30%) to avoid exacerbating lung damage, while maintaining O2 saturation above 90%
• Cisplatin toxicity includes nephrotoxicity, peripheral neuropathy, marked nausea and vomiting (black box warning), hypersensitivity reaction, myelosuppression, and ototoxicity
• Doxorubicin is toxic to the heart (cardiotoxicity) and can cause dose-related cardiomyopathy and arrhythmias from free radical formation disrupting cardiac proteins and cell membranes.