M6: Antineoplastics

Question 1

ATINEOPLASTICS
- Classes
- Indications
- Adverse Effects

Answer 1

MAJOR CLASSES:
1. Antimetabolites → cell cycle specific
2. Antimitotics → cell cycle specific
3. Alkylating agents
4. Topoisomerase inhibitors

MAIN INDICATIONS:
1. Combined with surgery and/or radiotherapy
2. Inoperable tumor
3. No response to radiotherapy
4. Use combinations
5. Follow regimen
6. Monitor: CBC – liver – renal functions

ADVERSE EFFECTS:
1. Alopecia
2. Bone marrow suppression →
Anemia – infection – bleeding
3. Cardiac: arrhythmias – HF
4. GI: nausea – vomiting – diarrhea
5. Hepatotoxic – nephrotoxic – neurotoxic
6. Teratogenic
7. Cytotoxic – mutagenic

Question 2

ANTIMETABOLITES
- Classes
- Mechanism

Answer 2

Analogues of normal cell metabolites (e.g., purines & pyrimidines bases)

CLASSES:
1. Purine analogues:
- 6-mercaptopurine (6-MP)

2. Pyrimidine analogues:
   - 5-fluorouracil (5-FU)
   - Cytosine arabinoside (Cytarabine)
3. Antifolates:
   - Methotrexate

MECHANISM:
1. Competitive decrease of these metabolites interfere with DNA & RNA synthesis
2. Arrest growth & division of malignant cells
3. During “S” phase of interphase

Question 3

METHOTREXATE
- Mechanism
- Indications
- Adminerstration

Answer 3

MECHANISM:
1. Folic acid analogue:
Decrease DHFR enzyme → decrease THF (essential for purine & pyrimidine bases)

INDICATIONS:
1. Cancer chemotherapy
2. Autoimmune diseases

ADMINERSTRATION:
Oral – parenteral

Question 4

ANTIMITOTICS
- Types
- Mechanism

Answer 4

• Plant alkaloids
• Target the mitotic (M) phase of cell cycle

MAIN TYPES:
1. Vinca alkaloids: e.g., vincristine – vinblastine

2. Taxanes: e.g., paclitaxel (taxol)

MECHANISM:
1. Microtubules:
- Tubulin protein polymers
- Mandatory for cell division

2. Antimicrotubule action:
   - Bind tubulin →
   - Vinca alkaloids: Decrease polymerization → prevent microtubules formation
   - Taxanes: stabilize microtubules → prevent separation of chromosomeMA

Question 5

ALKYLATING AGENTS
- Types
- Mechanism

Answer 5

TYPES:
1. Nitrogen Mustards:
DRUGS = cyclophosphamide, chlorambucil

2. Nitrosoureas:
   DRUGS = carmustine
3. Platinum-based drugs: alkylating-like agents
   DRUGS = cisplatin

MECHANISM:
1. Attach an alkyl group to DNA by a covalent bond →
- Cross-link DNA strands
- Strands are unable to uncoil
- Abnormal base-pairing: ALL leads to → DNA damage and cell death

Question 6

TOPOISOMERASE INHIBITORS

Answer 6

Topoisomerases:
1. Nuclear enzymes
2. Modulate DNA topology:
- Unwind & wind DNA strands
- Required for mRNA transcription & DNA replication

Topoisomerase I: cut & ligate single strand of DNA
DRUG = Irinotecan

Topoisomerase II: cut & ligate both strands of DNA
1. Antineoplastics:
DRUGS = doxorubicin, etoposide
2. Antibiotics: quinolones
- Inhibit bacterial topoisomerase II (DNA gyrase)

Action of topoisomerase inhibitors:
1. Block DNA ligation → DNA breaks → interrupt protein synthesis & cell division apoptosis

Question 7

OTHER ANTINEOPLASTICS

Answer 7

1. Antitumor Antibiotics:
   - Interfere with RNA & DNA synthesis interrupt tumor cell growth and reproduction

DRUGS = actinomycin – bleomycin

2. Hormones:
   - Selective suppression of tumor cells
   DRUGS = steroids – tamoxifen (anti-estrogen)
3. Retinoids:
   - Vitamin A analogues – stimulate apoptosis
   DRUGS = fenretinide
4. Antiangiogenic Agents:
   - Interfere with neovascularization
   - Interrupt tumor growth and spread

Question 8

Example of Chemotherapy in Certain Tumors

Answer 8

1. Breast cancer:
   - Doxorubicin + Cyclophosphamide ± Taxol

• Ti-II + Alkyl. agent ± Antimitotic

2. Acute lymphoblastic leukemia (ALL):
   - Vincristine + Dexamethasone + Asparaginase

• Antimitotic + Steroid + hydrolytic enzyme

3. Hodgkin Lymphoma:
   - Cyclophosphamide + Vincristine + Prednisone + Procarbazine hydrochloride

• Alkyl. Agent + Antimitotic + Steroid + Alkyl. Agent