Pharmacology Principles of Cancer Therapy

Question 1

Describe the Typical Common Adverse Effects of Cancer Drugs

Answer 1

1. Myelosuppression
2. Gastrointestinal Tract toxicity (Oral Mucositis)
3. Necrosis after extravasation
4. Peripheral Neuropathy- Spindle Poisons

Question 2

Describe the Mechanisms of Action of Cancer Drugs

Answer 2

Damage DNA
Alkylating agents
cytotoxic antibiotics
Prevent DNA synthesis
Antimetabolites
Inhibiton of driver oncogenes and cell signalling
Monoclonal Antibodies
Kinase Inhibitora
Immune Modulation
Checkpoint inhibitors, Interferons, IL-2
Prevent cmpletion of Mitosis
Spindle Poisons

Question 3

What do we know about cancer drugs?

Just give facts about cancer drugs

Answer 3

They have narrow therapeutic index
life threatneing toxixity
Combination Therapy
There can be Resistance
Given mostly in IV

Question 4

Antimetabolites

Describe the targets of the following drugs
1. Hydroxyurea
2. 5-fluorouracil
3. Gemcitabine Cytarabine
4. Methotrexate
5. 6-mercaptopurine

Answer 4

1. Hydroxyurea- Inhibits Ribonucleotide reductase
2. 5-Fluorouracil-Inhibits Thymidylate Synthase
3. Gemcitabine Cytarabine- Inhibits DNA synthesis and DNA polymerase
4. Methotrexate- Inhibits DHFR and blocks purine ring formation
5. 6-Mercaptopurine- Inhibits purine ring formation thus DNA synthesis

Antimetabolites Inhibit DNA synthesis

Question 5

Describe the Clinical Uses and Contraindications of Methotrexate

Answer 5

Contraindications
Liver and Renal
Clinical Uses
1. Acute Lymphoblastic Leukaemia
2. Burkitts Lymphoma
3. Chorio-carcinoma
4. Head and Neck tumours
5. Rheumatoid Arthritis

Question 6

Describe the Clinical Uses of Premetrexed

Answer 6

Pleural mesothelioma
Metastatic NSC lung cancer

Question 7

Describe the Adverse Reactions and Drug Interactions of MTX(Methotrexate) and Premetrexed

Answer 7

Adverse Reactions
Myelosuppression
Nepatotoxicity
Renal Failure
Pneumonitis
Mucositis
Stomatitis

Drug Interactions
NSAIDS, Omeprazole, Warfin, Penicillin, Ceph,

Question 8

Drugs that damage DNA

Give a list of Drugs that are Alkalating Agents and describe their MOA

Answer 8

1. Cyclophosphamide
2. Busulfan
3. Chlorambucil

Mech. Of Action
Alkylate DNA, Cross-link DNA-DNA
Cause Mispairing of Bases
Cause Depurination
and they trigger apoptosis

Question 9

Drugs that damage DNA

List the Drug classes under Cytotoxic Antibiotics

Answer 9

1. Anthracyclines
2. Dactinomycin
3. Bleomycin

Use DAB to remember this

Question 10

Cytotoxic Antibiotics

Describe the Adverse effects, MOA and list the drugs that are Anthracyclines

Anthracyclines are cytotoxic antibiotics

Answer 10

Adverse effects
cardiac toxicity
Acute use- Arrhythmias
Chronic use- Cardiomyopathy

Mech. Of Action
Increase free radicals and inhibit DNA topoisomerase

Include
1. Daunorubicin
2. Doxorubicin
3. Epirubicin
4. Idarubicin
rubicin

Question 11

Describe the MOA and Adverse Effects of Dactinomycin

Answer 11

Intercalate and block DNA transcription
Inhibits topoisomerase I and II
Avoids extravasation

Adverse Reactions
GIT Toxic

Question 12

Describe the MOA, Adverse Reactions of Bleomycin

Answer 12

MOA
Oxidative damage to thymidylate, free radical formation

Adverse Reactions
Anaphylactoid reactions, hyper-pigmentation, hyper-keratosis
causes fibrosis in the LUNGS

Question 13

There are Some plant products that are efficient topoisomerase inhibitors
two of these
NAME THEM

Answer 13

Podophylllotoxins (inhibits topoisomerase II)
1. Etoposide causes drug induced leukaemia
2. Tenoposide causes alopecia and myelosuppression

Camptothecins (Inhibit Topoisomerase I)
Irinotecan causes severe diarrhoea

Question 14

Describe the 2 classes of Microtubule Inhibitors (moa and drug names)

Answer 14

Vinca Alkaloids
Include Vincristine and Vinblastine
bind beta-tubulin and prevents binding with alpha-tubulin

Taxanes
Include Paclitaxel and Docetaxel
prevents depolymerisation

Peripheral neuropathy is a common ADR of microtubule inhibitors

Question 15

Kinase Inhibitors

Okay,
so Oncogenes code for kinases, which stimulate cell proliferation. That is why we need Kinase Inhibitors

Describe the 2 classes of kinase inhibitors and their drug interactions each.

Answer 15

Two Classes of Drugs
1. Monoclonal Antibodies: The Mabs. No possible drug interaction.
2. Small Molecule Inhibitors: The NIBS

The NIBS are prone to drug interactions-CYP metabolism
The nIBS risk for QT prolongation.

Question 16

Kinase Inhibitors

Describe the MOA, Mode of Admin, drug interactions, Indications and Adverse Effects for Imatinib

Answer 16

Oral Administration (300-600 mg/day)

Drug Interactions- CYP3A4

Indications
CML (BCR-ABL)
GIST (KIT mutation)
CMML

Adverse Effects
Myelosuppression
Congestive Heart Failure
Cardia Failure
Oedema

Question 17

Monoclonal Antibodies

Monoclonal antibodies bind and inhbit cell surface receptors. They stimulate the immune system to target and destroy the cells bound to the antibody.

Describe what protein( on which cells) the following antibodies bind to
Rituximab
Alemtuzumab
Cetuxumab
Ipilimumab

Answer 17

Rituximab binds to CD20 protein on Lymphocytes
Alemtuxuman binds to CD52 protein on immune cells
Cetuximab binds and blocks EGFR and its signalling
Ipilimumab binds to the CTLA-4 receptor and prevents the downregulation of T-cell activation

these are expensive

Question 18

targeting immune checkpoints(McAbs)

Describe the Indication and target(MOA) of Ipilimumab

Answer 18

Block CTLA-4 and B7 interaction to allow T-cell activation

Indications
Metastatic Melanoma

This has a slow onset of action

Question 19

targeting immune checkpoints (McAbs)

Describe the target(MOA) and Indication of Pembrolizumab

Answer 19

Indication:
Metastatic Melanoma

Target:
Blocks PD-1 and PDL1 interaction which allows T-cell activation to proceed.

Question 20

What are the side effects of McAbs?

Answer 20

Non-specific inflammation
if that happens, withhold treatment until inflammation subsides and give high dose corticosteroids.