Chemotherapy Drugs Flashcards
What are the different classes of chemotherapy drugs?
- Cytotoxic drugs ( alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivatives)
- Hormones
- Monoclonal antibodies
- Protein Kinase Inhibitors
What are the different classes of alkylating agents? (cytotoxic drugs)
- Nitrogen mustards - cyclophosphamide
- Nitrosoureas - lomustine (CCNU), carmustine (BCNU)
- Busulphan
- Platinum compounds - cisplatin, carboplatin
What are the different classes of antimetabolites? (cytotoxic drugs)
- Folate antagonists - eg. methotrexate
- Pyrimidine analogues - eg. fluorouracil
- Purine analogues - eg. fludarabine
What are examples of cytotoxic antibiotics? (cytotoxic drugs)
- Doxorubicin
- Bleomycin
What are examples of plant derivatives? (cytotoxic drugs)
- Vincristine
- Vinblastine
- Vindesine
What are the different classes of hormones?
- Glucocorticoids (eg prednisolone, dexamethasone) -
- Oestrogens (eg. diethylstilebestrol)
- Progestogens (eg. megesterol)
- Gonadotropin-releasing hormone analogues (eg goserelin)
- Anti-oestrogens (eg tamoxifen)
- Anti-androgens (eg. flutamide)
How do cytotoxic drugs work?
- They block DNA synthesis/prevent cell division
How do hormones (and their antagonists) work?
- They suppress opposing hormone secretion or inhibit their actions.
How do monoclonal antibodies work?
- They target specific cancer cells
How do protein kinase inhibitors work?
- They block cell signalling pathways in rapidly diving cells.
How do alkylating agents work? (cytotoxic drugs)
- Target cells in DNA synthesis phase (S-phase)
- Form covalent bonds with DNA (cross -linking) to prevent uncoiling (inhibits replication)
- SIDE EFFECTS - sterility (in men) ad increased risk of non-lymphocytic leukaemia (AML)
Explain nitrogen mustards (alkylating agents, CYTOTOXIC DRUGS)
- Have cytotoxic effects in rapidly growing cells - very reactive, given IV.
- Mechlorethamine
- Cyclophosphamide
- Melphalan
- Chlorambucil
- Bendamustine
- Estramustine
- SIDE EFFECTS - can cause cystitis (cyclophosphamide)
Explain nitrosoureas (alkylating agents, CYTOTOXIC DRUGS)
- Highly lipophilic - cross the BBB to treat CNS tumours.
- Carmustine (IV) - multiple myeloma, non-Hodgkins lymphoma and brain tumours
- Lomustine (oral) - Hodkins disease, malignant melanoma and certain solid tumours.
Explain platinum compounds (alkylating agents, CYTOTOXIC DRUGS)
- Cisplatin - testicular, lung, cervical, bladder etc
- Potent alkylator - binds to RNA>DNA>protein
- Binds to purine bases (G,A,U).
- Resistance may develop - DNA repair by DNA polymerase.
- SIDE EFFECTS - very nephrotoxic (requires hydration), severe N+V, risk of tinnitus, peripheral neuropathy, hyperuricaemia (gout) and anaphylaxis.
Explain other platinum compounds (platinum compounds > alkylating agents, CYTOTOXIC DRUGS)
- Carboplatin - derivative of cisplatin (ovarian and lung cancer).
- Less side effects- can be outpatient.
- Oxaliplatin - used to treat colorectal cancer (with fluorouracil and folinic acid).
- SIDE EFFECTS - bone marrow suppression (myelotoxic).
What other alkylating agents are there? (cytotoxic drugs)
- Busulfan - selective for bone marrow, leukaemia treatment.
- Procarbazine - used to treat Hodgkins disease but causes hypersensitivity rash and inhibits MAOIs :( -
- Trabecteolin - soft tissue sarcoma/advanced ovarian cancer but is hepatotoxic :(
Explain folate antagonists (antimetabolites, CYTOXIC DRUGS)
- Folate essential for DNA synthesis/cell division
- Methotrexate - inhibits dihydrofolate reductase (oral, IM, IV).
- Low lipid solubility (doesn’t cross BBB). Childhood acute lymphoblastic leukaemia, chariocarcinoma, non-Hodgkins and solid tumours
- Cautions - Mostly excreted in the urine - lower doses for patients with renal impairment, NSAIDs reduce excretion = increased toxicity
- Tumour cells may develop resistance.
- Given with folinic acid to ‘rescue’ normal cells.
- Also used to suppress immune system (arthritis)
Explain Pyrimidine Analogues (antimetabolites, CYTOTOXIC DRUGS)
- Compete with C and T bases which make up DNA and RNA - inhibits DNA synthesis.
- Fluorouracil (solid tumours, GI cancers and breast cancers)
- Capecitaine (colon/colorectal cancer, breast cancer)
- Cytarabine (acute myeloblastic leukaemia) -
- Gemcitabine (pancreatic/bladder/ovarian/breast cancer)
Explain purine analogues (antimetabolites, CYTOTOXIC DRUGS)
- Compete with A and C - inhibit purine metabolism
- Mercaptopurine
- Tioguanine
- Pentostatin
- Fludaraine
Explain doxorubicin (cytotoxic antibiotics, CYTOTOXIC DRUGS)
- Binds to RNA and inhibits DNA/RNA synthesis (IV) - acute myeloblastic leukaemia.
- Inhibit topoisomerase II (swivels DNA and introduces double strand breaks to prevent tangling and unwinds DNA for replication).
- SIDE EFFECTS - local necrosis if it touches skin, cardiac dysrhythmias/head failure in high doses
Explain bleomycin (cytotoxic antibiotics, CYTOTOXIC DRUGS)
- Degrades pre-formed DNA
- Active against non-dividing cells (Go phase) -
- Metastatic germ cell cancer/non-hodgkins
- SIDE EFFECTS - pulmonary fibrosis (10% patients), 50% develop mucocutaeneous reactions (mouth sores, hair loss, fungal infections) and pyrexia
What other cytotoxic antibiotics are there? (cytotoxic drugs)
- Dactinomycin - paediactric cancers
- Mitomycin - IV - upper GI and breast cancers.
Explain Vincristine, Vinblastine and Vindesine (Plant derivatives, cytotoxic drugs)
- Madagascar periwinkle
- Prevents polymerisation of tubulin (microtubules), prevents spindle formation ‘vinca alkaloids’
- Effects only occur during mitosis
- Relatively non-toxic (except vincristine - neuromuscular effects)
- All used to treat leukaemias, lymphomas and some solid tumours (breast and lung)
Explain Paclitaxel and Docetaxel (Plant derivatives, cytotoxic drugs)
- ‘Taxanes’ - yew tree
- similar mechanisms to vinca alkaloids
- Used to treat breast cancer and ovarian cancer (except docetaxel)
Explain etoposide (Plant derivatives, cytotoxic drugs)
- Mandrake root - testicular cancer/lymphomas -
- Avoid skin contact -
- Small cell carcinoma of bronchus
- SIDE EFFECTS - rapid fall in blood pressure
How are hormones used to treat cancer?
- Used in the treatment of cancers in hormone-sensitive tumours (breast, prostate, ovarian)
- Tumour growth inhibited by receptor antagonists, hormones with opposing actions, or drugs, which block synthesis of endogenous hormones.
- Rarely cure diseases but reduce symptoms
How are oestrogens used to treat cancers (Hormones)
- Ethinyloestradiol & Diethylstilbestrol
- Antagonists of androgen - dependant prostate cancer.
- Stimulates resting mammary cells to proliferate as proliferating cells are more susceptible to drugs.
- SIDE EFFECTS - nausea, fluid retention, thrombosis, impotence and gynaecomastia.
How are progestogens used to treat cancers? (hormones)
- Megestrol
- Medroxyprogesterone
- Norethisterone - Used to treat endometrial cancer.
How are GnRH analogues used to treat cancers? (Hormones)
- Goserelin
- Buserelin
- Leuprorelin
- Triptorelin
- Inhibit GnRH research to decrease LH/FSH to decrease testosterone.
- Used to treat prostate/breast cancer.
How are Somatostatin analogues used to treat cancer? (hormones)
- Octreotide
- Lanreotide
- Inhibit cell proliferation/hormone (CCK/Gastrin) secretion.
- Used to treat hormone-secreting tumours of GI tract.
How is tamoxifen used to treat cancers? (hormone antagonists, HORMONES)
- Competitive antagonists of oestrogen receptors to inhibit transcription of oestrogen-responsive genes> breast cancer treatment.
- SIDE EFFECTS - menopausal effects, endometrial cancer and increased risk of blood clots
How is Letrozole and Exemastine used to treat cancers? (hormone antagonists, HORMONES)
- Inhibit aromatase (enzyme involved in oestrogen synthesis).
- This blocks the conversion of adrogens to oestrogens in peripheral tissue but does not inhibit ovulation.
How is flutamide, cyproterone and bicalutamide used to treat cancers? (hormone antagonists, HORMONES)
- Androgens antagonists - prostate cancer treatment.
How is prednisolone and dexamethasone used to treat cancer? (glucocorticoids, HORMONES)
- Inhibit lymphocyte proliferation - treatment of lymphomas/leukaemias.
- Counter some side effects of other anti-cancer drugs (N+V)
How are monoclonal antibodies used to treat cancer?
- Produced by cultured-hybridoma cells (formed by fusing anti-body producing b-cells with b-cell cancer (myeloma)).
- React with specific target proteins expressed on cancer cells - activates immune system - lysis of cancer cells.
- Some mAbs activate GF-receptors on cancer cells - inhibit survival/promote apoptosis.
- Targeted therapy - less side effects
- expensive, must be given in combination with other drug.
How is Rituximab used to treat cancer (Monoclonal antibodies)
- Binds to CD20 protein, expressed on certain lymphoma cells - lysis of b-lymphocytes
- 40-50% effective when used with chemotherapy.
- Used to treat Non-Hodgkins lymphoma expressing CD20.
- SIDE EFFECTS - hypotension, chills and fever, hypersensitivity.
How is Trastuzumab used to treat cancer? (monoclonal antibodies)
- Binds to HER2 (a GF-receptor)
- Induces immune response and cell cycle inhibitors
- HER2 overexpressed in ~25% breast cancer = rapid proliferation (aggressive form)
- Given with standard drugs to increase survival rate.
- SIDE EFFECTS - tremor, flu-like symptoms, itchy eyes, BP changes, palpitations.
How is Bevacizumab used to treat cancer? (monoclonal antibodies)
- Treatment of colorectal cancer.
- Neutralises VEGF (overexpressed in tumours) prevents angiogenesis (IV)
How are Imatinib, Dasatinib** and **Nilotinib used to treat cancer? (Protein Kinase Inhibitors)
- Blocks tyrosine kinases involved in GF signalling pathways (oral)
- Used to treat chronic myeloid leukaemia (CML)
- Problems with drug resistant.
Control of Side effects of cancer drugs
- N+V - Ondansetron, Granisetron, Metaclopramide
- Anxiety - Lorazepam
- Myelosuppression - Stem cell transplant, Lenagrastim.
Side effects of cancer chemo:
Are minimised by treatment with anti-emetics and good nursing care.
What is the mechanism of action for the majority of anti-cancer drugs?
Prevention of cell division.
Bulsafan is an alkylating agent which is selective for bone marrow. It is therefore used in the treatment of:
Leukaemia.
As a treatment for cancer, monoclonal antibodies are different from other drugs because they;
Selectively improve host immunity.
