Antineoplastic drugs Flashcards
What is a neoplasm?
A neoplasm is a mass of excess tissue formed by an unexplained, uncoordinated high rate of cell proliferation exceeding the cell death rate.
AKA tumor.
What are the types of tumors?
Benign (non-cancerous) and malignant (cancerous)
What is a malignant tumor?
A malignant tumour can invade and damage nearby tissues/organs or breakaway and travel through the blood stream or lymphatic system to form new tumour cells (i.e., metastases).
What are secondary tumours?
They are new tumour cells that form as a result of the invasion of the cells of the primary malignant tumour.
Secondary tumours are named based on where they are found. True or false?
False.
A secondary tumour has the same name as the primary tumour since it has the same kind of abnormal cells.
What is the phase cycle?
The phase cycle refers to the stages a cell goes through during its growth.
What are the phases of the cell cycle?
- M = Mitosis and cell division phase
- G0 = Resting state
- G1 = Post resting state (normal metabolism)
- S = DNA synthesis, in preparation for mitosis
- G2 = Premitotic phase (protein synthesis)
What is doubling time?
The average interval between successive mitoses is called doubling time.
What is the relevance of doubling time in cancer therapy?
Doubling time determines percent kill for remission (90-99%).
What are the causes of cancer?
- Chemicals
- Radiation
- Certain viruses
- Genetic predisposition
- Lifestyle factors
- Idiopathy
Examples of cancer-causing chemicals
Pesticides, tobacco, arsenic, polycyclic hydrocarbons, solvents, and drugs like tamoxifen, etc.
Examples of cancer-causing viruses
HPV, HBV, HCV, HIV
What are the treatment options for cancer?
- Surgery (before metastasis)
- Radiotherapy (may destroy normal cells)
- Immunotherapy
- Chemotherapy
When is chemotherapy used?
- as primary treatment
- before or after surgery or radiotherapy as adjuvant
- as palliative treatment to minimize discomfort and slow progression of the disease
Describe the toxicity of antineoplastic drugs
They attack both neoplastic and normal cells because the two are similar in composition and activity.
Tissues most affected are the highly proliferative ones (with high growth fraction), e.g., bone marrow, lymphoblasts, mucous membranes, skin, gonads, etc.
Some interfere with genetic mechanisms and are therefore mutagenic; others are teratogenic.
How can one reduce the effects of toxicity?
Through good nutrition or discontinuation of the therapy
What are the symptoms of toxicity?
Neutropenia, thrombocytopenia, G.I. ulceration, alopecia, amenorrhea, immunosuppression, nausea, vomiting, diarrhoea, cramping, hyperuricemia, etc.
What are the categories of antineoplastic drugs?
- Cell cycle phase-specific
- Cell cycle phase non-specific
What are the classes of antineoplastic drugs?
- Alkylating agents
- Antimetabolites
- Hormonal agents
- Antitumour antibiotics
- Plant alkaloids
Which classes are cell cycle phase-specific?
- Antimetabolites: specific to the S phase (DNA synthesis)
- Plant alkaloids: specific to the M phase (Mitosis)
What are the sub-classes of alkylating agents?
- Nitrogen mustards
- Nitrosoureas
- Alkylsulphonates
- Ethyleneimines
- Platinum complexes
What is the MOA of alkylating agents?
They cause cytotoxicity by reacting with the nucleophilic centre at the N7 position of guanine in DNA strand.
A bifunctional group will react with a 2nd guanine group of the 2nd strand of DNA, causing inter-strand cross-linking, leading to impaired template function for further replication.
How do cancer cells acquire resistance to alkylating agents?
- Increased ability to repair DNA lesions
- Decreased permeability to the alkylating drug
- Increased production of glutathione for direct detoxification
- Increased glutathione S-transferase, which catalyses the conjugation of the drug.
Alkylating agents are highly toxic. True or false?
True
