Chemotherapy Drugs Flashcards
(44 cards)
1
Q
What are the different classes of chemotherapy drugs?
A
- Cytotoxic drugs ( alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivatives)
- Hormones
- Monoclonal antibodies
- Protein Kinase Inhibitors
2
Q
What are the different classes of alkylating agents? (cytotoxic drugs)
A
- Nitrogen mustards - cyclophosphamide
- Nitrosoureas - lomustine (CCNU), carmustine (BCNU)
- Busulphan
- Platinum compounds - cisplatin, carboplatin
3
Q
What are the different classes of antimetabolites? (cytotoxic drugs)
A
- Folate antagonists - eg. methotrexate
- Pyrimidine analogues - eg. fluorouracil
- Purine analogues - eg. fludarabine
4
Q
What are examples of cytotoxic antibiotics? (cytotoxic drugs)
A
- Doxorubicin
- Bleomycin
5
Q
What are examples of plant derivatives? (cytotoxic drugs)
A
- Vincristine
- Vinblastine
- Vindesine
6
Q
What are the different classes of hormones?
A
- Glucocorticoids (eg prednisolone, dexamethasone) -
- Oestrogens (eg. diethylstilebestrol)
- Progestogens (eg. megesterol)
- Gonadotropin-releasing hormone analogues (eg goserelin)
- Anti-oestrogens (eg tamoxifen)
- Anti-androgens (eg. flutamide)
7
Q
How do cytotoxic drugs work?
A
- They block DNA synthesis/prevent cell division
8
Q
How do hormones (and their antagonists) work?
A
- They suppress opposing hormone secretion or inhibit their actions.
9
Q
How do monoclonal antibodies work?
A
- They target specific cancer cells
10
Q
How do protein kinase inhibitors work?
A
- They block cell signalling pathways in rapidly diving cells.
11
Q
How do alkylating agents work? (cytotoxic drugs)
A
- 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)
12
Q
Explain nitrogen mustards (alkylating agents, CYTOTOXIC DRUGS)
A
- Have cytotoxic effects in rapidly growing cells - very reactive, given IV.
- Mechlorethamine
- Cyclophosphamide
- Melphalan
- Chlorambucil
- Bendamustine
- Estramustine
- SIDE EFFECTS - can cause cystitis (cyclophosphamide)
13
Q
Explain nitrosoureas (alkylating agents, CYTOTOXIC DRUGS)
A
- 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.
14
Q
Explain platinum compounds (alkylating agents, CYTOTOXIC DRUGS)
A
- 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.
15
Q
Explain other platinum compounds (platinum compounds > alkylating agents, CYTOTOXIC DRUGS)
A
- 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).
16
Q
What other alkylating agents are there? (cytotoxic drugs)
A
- 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 :(
17
Q
Explain folate antagonists (antimetabolites, CYTOXIC DRUGS)
A
- 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)
18
Q
Explain Pyrimidine Analogues (antimetabolites, CYTOTOXIC DRUGS)
A
- 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)
19
Q
Explain purine analogues (antimetabolites, CYTOTOXIC DRUGS)
A
- Compete with A and C - inhibit purine metabolism
- Mercaptopurine
- Tioguanine
- Pentostatin
- Fludaraine
20
Q
Explain doxorubicin (cytotoxic antibiotics, CYTOTOXIC DRUGS)
A
- 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
21
Q
Explain bleomycin (cytotoxic antibiotics, CYTOTOXIC DRUGS)
A
- 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
22
Q
What other cytotoxic antibiotics are there? (cytotoxic drugs)
A
- Dactinomycin - paediactric cancers
- Mitomycin - IV - upper GI and breast cancers.
23
Q
Explain Vincristine, Vinblastine and Vindesine (Plant derivatives, cytotoxic drugs)
A
- 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)
24
Q
Explain Paclitaxel and Docetaxel (Plant derivatives, cytotoxic drugs)
A
- ‘Taxanes’ - yew tree
- similar mechanisms to vinca alkaloids
- Used to treat breast cancer and ovarian cancer (except docetaxel)
25
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
26
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
27
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.
28
How are **progestogens** used to treat cancers? (hormones)
* **_Megestrol_**
* **_Medroxyprogesterone_**
* **_Norethisterone_** - Used to treat endometrial cancer.
29
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.
30
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.
31
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
32
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.
33
How is **flutamide, cyproterone** and **bicalutamide** used to treat cancers? (hormone antagonists, HORMONES)
* Androgens antagonists - prostate cancer treatment.
34
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)
35
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.
36
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.
37
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.
38
How is **Bevacizumab** used to treat cancer? (monoclonal antibodies)
* Treatment of colorectal cancer.
* Neutralises VEGF (overexpressed in tumours) prevents angiogenesis (IV)
39
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.
40
Control of Side effects of cancer drugs
* N+V - **_Ondansetron, Granisetron, Metaclopramide_**
* Anxiety - **_Lorazepam_**
* Myelosuppression - Stem cell transplant, **_Lenagrastim._**
41
Side effects of cancer chemo:
Are minimised by treatment with anti-emetics and good nursing care.
42
What is the mechanism of action for the majority of anti-cancer drugs?
Prevention of cell division.
43
**Bulsafan** is an alkylating agent which is selective for bone marrow. It is therefore used in the treatment of:
Leukaemia.
44
As a treatment for cancer, monoclonal antibodies are different from other drugs because they;
Selectively improve host immunity.
