Chemotherapy drugs Flashcards Preview

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Flashcards in Chemotherapy drugs Deck (28):
1

What is cancer?

Uncontrolled proliferation of a normal cell
Turns into a tumour-
- could metastasise
- invasive/not invasive
Caused by DNA mutation
Causes: inherited eg BRCA1/2 gene in breast, viruses, carcinogens, alcohol, sun exposure

2

Normal cell growth regulation

Growth factors = specific receptors/signalling pathways
Cell cycle transducers
Apoptic genes = programmed cell death in ageing/normal cells
Telomeres = cap xsomes (shorten with age until replication stops)

3

Oncogenes

Proto oncogene can mutate into an oncogene, it is a protein which can cause:
- incressed cell division
- increased cell differentiation
- decreased cell death
Oncogenes are anti-apoptopic = cell survival

4

Cell mutations leading to cancer

In promoter region increased transcription
Gene amplification = increased copies of proto-oncogene
Xsome translocation = proto-oncogene moved to a site more likely for gene expression
Fusion of onco-gene with another gene with increased activity

5

Tumours

Mutations in apoptotic genes
Telomerase expressed = enzyme which stabalizes telomered
Overexpression of growth factors = unrestrained cell growth
Angiogenesis occurs - growth of new blood vessels

6

Metastasis

Primary tumour
- produces enzymes that break down ECM
Invades nearby tissue
Angiogenisis
- cells transported via new blood/lymphatic system
Secondary tumour

7

What are the 3 aims of cancer therapy?

Curing patient
Prolonging life
Palliative therapy

8

Compartments of tumours

Solid tumours, cells occupy 1 of 3 compartments
A = dividing cells
B = resting cells capable of division
C = cells no longer dividing but contribute to tumour volume

9

Toxic effects of chemo

Drugs affect all rapidly dividing tissues
- bone marrow supression
- impaired wound healing
- loss of hair
- damage ro GI epithelium
- stuntes growth
- sterility
- teratogenicity

10

Targets for anti-cancer drugs?

Hormonal regulation of tumour growth
Defective cell cycle controls

11

Alkylating agents in anti-cancer drugs
CYTOTOXIC

Block DNA synthesis
Targets cells in S phase
Form covalent bonds with DNA to prevent uncoiling and inhibit replication
SE with prolonged use: sterility, increased risk of non-lymphocytic leukaemia

12

What are the 4 types of alkylating agents?

Nitrogen mustards-
Eg Cyclophosphamide
- prodrug, given orally, activated in liver to phosphoramide + acrolein
- acrolein = haemorrhagic cystitis
Eg Mechlorethamine
-i.v, v reactive
Nitrosoureas -
- highly lipophillic = CNS tumours
Eg Lomustine (orally), Carmustine (iv)
Platinum compounds-
Eg Cisplastin
- v potent, binds to RNA>DNA>protein
- binds to G, A, U
- resistance may develop = DNA repair by DNA polymerase
- testicular/ovarian cancer, given iv
- SE = severe nausea, vomiting, peripheral neuropathy
Eg Carboplatin
Busulphan

13

Antimetabolites
- CYTOTOXIC
- folate antagonists

Methotrexate
- given orally, i.m, i.v, low lipid solubility
- NSAIDs can decrease excretion = increase toxicity
- can develop resistance
In high doses given with folinic acid to rescue normal cells
Suppresses immune system

14

Antimetabolites
- CYTOTOXIC
- pyrimidine analogues

Compete with C and T bases which make up RNA and DNA = inhibit synthesis
Eg Fluorouracil
Less well absorbed compared to Methotrexate

15

Antimetabolites
- CYTOTOXIC
- purine anologues

Compete with A and G bases = inhibit purine metabolism
Eg Fludarabine
Used mainly in leukaemia

16

Cytotoxic antibodies
- CYTOTOXIC

Eg Doxorubicin
- binds to DNA, inhibits RNA/DNA synthesis
- inhibits topoisemerase ll
SE= cardiac dyasrhythmias , heart failure in high doses
Eg Blecmycin
- degrades pre-formed DNA
- active against non-dividing cells
- 50% patients develop mouth sores, hair loss

17

Plant derivatives
- cytotoxic
Vinca alkaloids

Eg Vincristine, Vinblastine
- prevents polymerisation of tubulin = prevents spindle formation
- effects occur in mitosis

18

Plant derivatives
- cytotoxic
- taxanes

Eg Paclitaxel
- used to treat advanced breast/ovarian cancer

19

Hormones in anti-cancer drugs

Used to treat cancers in hormonw sensitive tissues (breast prostate ovaries)
Tumour growth inhibited by R antagonist, hormones with opposing actions, on drugs which block synthesis of endogenous hormones
Rarely cure disease but decrease symptoms

20

Oestrogens - hormones

Eg Ethinyloestradiol + Diethystilbestrol
- antagonist of androgen-dependant prostate cancer (palliative care)
- SE = nausea, fluid retention, impotence

21

Progestogens - hormones

Eg Northisterone, Megesterol
- used to treat endometrial cancer

22

GnRH anologues

Eg Goserlin
- inhibit GnRh release = decrease LH/FSH to decrease testosterone
- used to treat prostate/advanced breast cancer

23

Hormone antagonists

Eg Tamoxifen
- competative antagonist at oestrogen receptors- inhibits transcription of oestrogen responsive genes
- breast cancer treatment
- adverse affects similar to menopause, endometrial cancer, increased risk of blood clots

24

Glucocorticoids - hormones

Eg Prednisolone, Dexamethasone
- inhibit lymphocyte proliferation = used in treatment of leukaemia /lymphomas
- counter some SE of other drugs
- used in supportive/palliative care

25

Monoclonal antibodies in anti-cancer drugs (immunotherapy)

Produced by cultured hybridoma cells
React with specific target proteins expressed on cancer cells = activates immune system = lysis of cancer cells
Some inhibit survival/promote apoptosis
Targeted therapy = decreased SE
Expensive, given in combination with other drugs

26

Rituximad - monoclonal antibody

Lysis of B lymphocytes
Can cause chills, fever, hypotension

27

Trastuzumab (Herceptin) - monoclonal antibody

Induces immune response + cell cycle inhibitors
Given witn standard drugs increases survival rate
SE= tremor, flu-like symptoms, BP changes, palpitations

28

Control of side effects

Nausea and vomiting:
- decrease patient compliance
- Ondansetron/Graniestron 5HT3 receptor antagonists effective s cytotoxic drug induced vomiting
- Metaclopramide
Anxiety:
- Lorazepam
Myelosuppression:
- stem cell transplant
- stem cells harvested from patient and infused back after chemo