Describe the TNM system
- T = tumour size (0-4)
- N = lymph node involvement (0-3)
- M = metastasis (0-1)
Describe the role of surgery for cancer
- *Remission is usually used rather than cured
- Useful for reducing tumour mass and curative if all cancerous cells are removed
- Tissue removed examined by pathologist to ensure that a margin of healthy tissue was also removed
- Surgery may be necessary for determining tumour size and extent of metastases in order to accomplish staging
- May be useful as a palliative tx to relieve conditions such as spinal cord compression
What determines the dose of radiation?
- Type of cancer
- Proximity of sensitive tissue or organs
- Constitution of pt
What are the goals of combination chemotherapy?
- Synergy between some of the agents
- Reduce possibility of resistance developing
- Reduce dose-related adverse effects
What is the IT route? When is it used? When is it contraindicated?
- Intrathecal route (injection into CSF) is used in order to get the agent across BBB
- IT route absolutely CI for a number of antineoplastic drugs such as vinca alkaloids which will result in px death
Mechanism of alkylating agents
- Inhibit DNA replication by causing cross-linking and abnormal base pairing of DNA strands
- Can form a highly electrophilic immonium ion which can covalently bind to a nucleophilic compound like N-7 nitrogen of guanine
- Resulting inter or intra-strand cross-linking makes the DNA non-functional
Why are alkylating agents toxic?
Able to react w/ any cell component containing nucleophilic groups such as hydroxyl, sulfhydryl, amino, or carbonyl
How can cancer cells become resistant to chemotherapy?
- Increased ability to repair DNA lesions
- Decreased permeability to agents
- Increased production of glutathione which reacts w/ alkylating agents
Adverse effects of alkylating agents
- Myelosuppression w/ granulocytopenia
- Thrombocytopenia and anemia
- N/V
- Reversible hair loss
Mechanism of anti-metabolites
- Structural analogues of naturally occurring substrates for biochemical reactions occurring in the body
- Several act as false substitutions in the production of nucleic acids and stop replication process
Mechanism of antibiotics as chemotherapy
- Intercalation
- Sliding between DNA base pairs and inhibiting DNA synthesis
Mechanism of vinca alkaloids
Prevent formation of mitotic spindle and stop cell division
Mechanism of platinum compounds? What are examples?
- Act in a similar manner as the alkylating agents
- Group includes cisplatin and carboplatin
Which normal cells are more sensitive to anti-neoplastic drugs?
Those w/ higher turnover rates (ex: bone marrow, mucous membranes, hair follicles)
Common toxicities of anti-neoplastics?
- Myelosuppression
- Mucositis (mouth sores, diarrhea)
- Alopecia
Onset of myelosuppression
- Usually 7-10 days after tx
- Lowest cell counts seen 10-14 days after tx
How long does it take for myelosuppression to return to normal?
Usually 2-3 weeks
3 most common effects of myelosuppression
- Neutropenia or reduction in # of neutrophil WBCs predisposes pt to infections
- Thrombocytopenia or reduction in # of platelets can lead to bleeding
- Anemia secondary to chemotherapy not as common due to long lifespan of erythrocytes (~120 days)
How can neutrophil counts return to normal faster?
- Administration of growth factors G-CSF (filgrastim)
- May prevent febrile neutropenia and allow therapy to continue at full doses
What factors can increase risk of N/V from anti-neoplastics?
- Hx of motion or pregnancy-related nausea
- Female
- Fatigue
- Age < 50 y/o
- Lower performance status (general health)
What are the 3 categories of chemotherapy-induced N/V
- Acute
- Anticipatory
- Delayed
Describe acute chemotherapy-induced N/V
- Sx begin 1-2 h after administration
- Peak after 4-6 h and then subside after 12-24 h
- Due to stimulation of chemoreceptor trigger zone through serotonin release
- Serotonin antagonists (ondansetron) helpful
- Anti-emetic therapy must be individualized for each pt
Describe anticipatory chemotherapy-induced N/V
- Nausea triggered by stimuli associated w/ therapy (ex: smell or sight of hospital)
- Managed w/ relaxation techniques, attention diversion, aromatherapy, and anxiolytics (ex: lorazepam)
- Effective preventative strategy is ensuring good acute phase control
Describe delayed chemotherapy-induced N/V
- Begins at least 24 h after chemotherapy administration
- May persist 2-5 days
- Mechanism not understood but usually seen w/ highly emetogenic drugs like cisplatin
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1 - Toxicokinetics34
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2 - General Methods for Overdose46
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3 - Acid/Base Disturbances28
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4 - Acetaminophen25
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5 - Salicylates24
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6 - Iron29
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7 - Forensics Overview32
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8 - Forensic Aspects of Drug Abuse 133
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9 - Forensic Aspects of Drug Abuse 211
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10 - Forensic Aspects of Drug Abuse 320
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11 - Medico-Legal Aspects of Common Poisons25
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13 - Toxic Alcohols32
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14 - Digoxin15
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15 - Benzodiazepines24
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16 - Antineoplastic Agents39
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17 - Antidepressants42
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18 - Ototoxicity16
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19 - Blood59
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20 - Ocular Toxicity37
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21 - Nephrotoxicity23
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22 - Skin42
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23 - Hepatotoxicity8
