LT16+17 - Pharmacology, core medication list

Question 1

3 forms of cancer treatment

Answer 1

surgery, radiotherapy, pharmacological therapy

Question 2

4 options of pharmacological therapy

Answer 2

• cytostatics
• hormones
• immunumodulators
• target therapy

Question 3

Cell cycle

Answer 3

G1 phase –> S-phase –> G2 phase –> M-phase

Question 4

G1 phase

Answer 4

SNA systhesis

Question 5

S-phase

Answer 5

DNA replication

Question 6

G2 phase

Answer 6

cell prepares for mitosis

Question 7

M-phase

Answer 7

DNA split in daughter cells

Question 8

Different cytostatic drugs + functions

Answer 8

• Alkylating drugs: interfere in all 4 phases
• Antimetabolites: interfere in the S-phase
• Intimitotics: interfere in mitosis
• Topo-isomerase inhibitors: interfere in G2-phase

Question 9

Different cytostatic drugs + function

Answer 9

• Alkylating cytostatics
• Antimetabolites
• Intimitotics
• Topo-isomerase inhibitors

Functions: induce damage to DNA and initiate apoptosis

Question 10

Alkylating cytostatics mechsanism

Answer 10

• Interfere in all 4 phases

- Prevent unwinding by helicases –> apoptosis

Question 11

Alkylating cytostatics examples

Answer 11

Cyclophosphamide

• Indication: solid tumors
• Oral or IV
• Side effects: nausea, vomiting, myelosuppresion

Cisplatin

• Indication: solid tumors
• Side effects: neusea, vomiting, neurotoxicity, acute nephrotoxicity, (myelosuppression is relatively low)

Question 12

Antimetabolites mechanism

Answer 12

• interfere in the S-phase

- Inhibit enzymes that cause synthesis from thymide to uracil

Question 13

Antimetabolites examples

Answer 13

Methotrexate

• inhibits dihydrofolate reductase
• IV preferred

5-Fluorouracil (5-FU)
- prodrug that becomes active by enzymes in the liver

Cytorabine
- Blocks DNA polymerase function –> inhibit DNA replication

Question 14

Antimetabolites side effects

Answer 14

Mucositis, myelosuppression, diarrhea

Question 15

Antimitotics (mitose inhibitors) mechanism

Answer 15

• interfere in mitosis
• Antimitotics can block microtubule formatioin, which is important for division of chromosomes into 2 daughter cells –> no cell division

Question 16

Antimitotics (mitose inhibitors) examples

Answer 16

• paclitaxel
• vinblastine
• vincristine

Question 17

Antimitotics (mitose inhibitors) side effects

Answer 17

preipheral oedema, alopecia, bone marrow suppression, hypersensitivity reactions, cardiac disturbances

Question 18

Topo isomerase inhibitors mechanism

Answer 18

• interfere in G2-phase

- inhibition of topoisomerases –> no unwinding and mitosis

Question 19

Topo isomerase inhibitors example

Answer 19

• Doxorubicine

- Etoposide

Question 20

Topo isomerase inhibitor side effects

Answer 20

Myelosuppression, vomiting, nausea, alopecia, cardiotoxicity

Question 21

limitation of cytostatics

Answer 21

Emesis (=nausea & vomiting)

Question 22

how is vomiting induced by cytostatics?

Answer 22

Cytostatics –> trigger via chemo trigger zone (CTZ) –> stimulation of the vomiting centre –> vomiting

Question 23

Anti-emetics mechanism

Answer 23

They block receptors in the CTZ

Question 24

Enti-emetics examples

Answer 24

5-HT3 receptor antagonists

• odansetron
• granisetron

D2 receptor antagonist
- metoclopramide

Question 25

Why can patients develop resistance against anti-emetics?

Answer 25

- Decreased amount of drug taken up by the tumor cell: transmembrane proteins may be changed (e.g. methotrexate) - Insufficient activation of the prodrug in the liver (e.g. fluorouracil to FDUMP) - Increased inactivation of a drug in the liver (increased elimination) - Increased concentration of the target enzyme (e.g. methotrexate) - Rapid repair of drug-induced lesions (e.g. alkylating agents) - Altered activity of target enzyme such as topoisomerase II (e.g. doxorubicin) - Mutation of various genes

Question 26

Limitations of cytostatic drugs?

Answer 26

- Dose limitation because of organ toxocity - Some tumors are insensitive/ have resistance - Systemic toxicity - Cytostatics are not specific for cancer celsl

Question 27

Solution to the limitation that cytostatics are not specific for cancer cells:

Answer 27

adding target therapy

Question 28

Soorten target therapy

Answer 28

- Monoclonal antibodies | - Proteine kinase inhibitors

Question 29

Monoclonal antibodies mechanism

Answer 29

bind to receptors of immune cells --> immune system can recognize them

Question 30

Monoclonal antibodies examples

Answer 30

- Tratuzumab - Ceruximab - Bevacizumab

Question 31

Tratuzumab mechanism

Answer 31

- antibody against HER2 - HER2 is a growth factor in mamma carcinoma's - inhibition of tumor cell proliferation by NK-cells and macrophages

Question 32

Tratuzumab side effects

Answer 32

Cardiomyopathy

Question 33

Cetuximab mechanism

Answer 33

- Antibody against EGF - EGF is a growth factor in epithelial cancer - inhibition of tumor cell proliferation by cytotoxic T-cells

Question 34

Cetuximab side effects

Answer 34

- allergic reactions, acne, dry skin

Question 35

Bevacizumab mechanism

Answer 35

- Antibody against VEGF factor | - anti-angeogenesis drug

Question 36

Bevacizumab side effects

Answer 36

- hypertension, proteinuria, bleeding

Question 37

Proteine kinase inhibitors mechanism

Answer 37

target intracellulary, decrease the expression of growth factors

Question 38

Proteine kinase inhibitor example

Answer 38

Imatinib

Question 39

Imatinib mechanism

Answer 39

inhibition of cell proliferation, induces apoptosis

Question 40

Imatinib side effects

Answer 40

headache, nausea, vomiting, diarrhea, dyspepsia