Pharmacology Flashcards- Hematology Agents (IRAT 9)

What is the order of the cell cycle?

G1 → S → G2 → M

What does CCNSA stand for?

Cell-Cycle Non-Specific Agents

What chemotherapy drug classes are CCNSA?

Alkylators, Platinum agents, Anthracyclines

What does CCSA stand for?

Cell-Cycle Specific Agents= Phase-specific

Give examples of CCSA: Phase-specific medications:

1. S: Antimetabolites

2. M: Vincas, Taxanes

3. G2: Bleomycin

🧪 Alkylating Agents:
What is the mechanism of action of alkylating agents?

Forms DNA cross-links → inhibits DNA synthesis & function

Do alkylating agents require activation?

Yes — require hepatic bioactivation (liver)

Give examples of Alkylating Agents:

1. Cyclophosphamide

2. Ifosfamide

3. Busulfan
   
   
   *less important

4. Mechlorethamine

5. Melphalan

6. Chlorambucil

7. Bendamustine

8. Altretamine

9. Thiotepa

How do alkylating drugs work?

Add alkyl groups to DNA → DNA damage → stops replication → cell death.

Bifunctional Alkylation

Q: What is bifunctional alkylation? Effect?

Two DNA bonds → cross-links DNA.
Blocks strand separation → strong cytotoxicity.

Monofunctional Alkylation

Q: What is monofunctional alkylation? Effect?

A: One DNA bond → DNA instability; DNA breaks → eventual cell death.

What are the key indications for alkylating agents?

1. Leukemia

2. Lymphoma

3. Multiple myeloma

4. Breast cancer & Ovarian cancer

5. Rheumatoid arthritis (RA)

6. Rapidly progressive glomerulonephritis (RPGN)

What are common side effects of alkylating agents?

• Nausea & vomiting

• Myelosuppression (↓ WBC, ↓ platelets, ↓ Hgb)

• Alopecia

• Infertility

• Secondary malignancies (AML)

What is the hallmark toxicity of Busulfan?

A: Pulmonary fibrosis
(+ adrenal insufficiency)

Key toxicities of Trabectedin?

Cardiotoxicity + ILD

Key toxicity of Altretamine?

Peripheral neuropathy + flu-like symptoms

Key toxicity of Lurbinectedin?

Hepatotoxicity

**Which alkylators cause hemorrhagic cystitis? Prevention?

Cyclophosphamide & Ifosfamide; Mesna + hydration

Core contraindications for alkylating agents?

• Pregnancy

• Severe myelosuppression

• Active infection / live vaccines

• Severe renal impairment

Which organ dysfunctions contraindicate alkylating agents (esp. busulfan, cyclophosphamide)?

Severe hepatic impairment

List Platinum Analogs:

1. Cisplatin

2. Carboplatin

3. Oxaliplatin

What is the MOA of Platinum Analogs (Cisplatin, Carboplatin, Oxaliplatin)?

Forms intra- and inter-strand DNA cross-links → prevents DNA from unwinding → blocks replication & repair; also binds nuclear and cytoplasmic proteins → additional cell damage

What cancers is cisplatin used for?

• Testicular

• Ovarian

• Bladder

• Lung

• Head & neck

• Esophageal

• Cervical

What cancers is carboplatin used for?

• Ovarian

• Lung

• Head & neck

• Lymphoma

What cancers is oxaliplatin used for

• Colorectal

• Pancreatic

• Gastric

What are hallmark toxicities of cisplatin?

• Nephrotoxicity → prevent w/ hydration + amifostine

• Ototoxicity

• Peripheral neuropathy

• Nausea & vomiting

⚠ Adverse Effects — Carboplatin

Q: Key toxicity of carboplatin?

Myelosuppression (greater than cisplatin)

⚠ Adverse Effects — Oxaliplatin

Q: Key toxicity of oxaliplatin?

• Peripheral neuropathy (cold-induced)

• Laryngopharyngeal dysesthesias

• Electrolyte abnormalities (hypomagnesemia, hypokalemia)

Contraindications — Platinum Agents

• Pregnancy

• Severe renal impairment

• Pre-existing neuropathy (esp. oxaliplatin)

• Severe myelosuppression

• Active infection

Give examples of Anthracylclines:

1. Doxorubicin

2. Daunorubicin

3. Epirubicin

4. Idarubicin

5. Mitoxantrone

What is the mechanism of anthracyclines (e.g., doxorubicin)?

• Intercalate DNA

• Inhibit topoisomerase II

• Generate free radicals → DNA damage

Anthracyclines slip into DNA and block it from working, trap topoisomerase II so DNA gets cut but not repaired, and generate free radicals that further damage DNA and cell membranes — all leading to cancer cell death.

🎯 Indications

What are key indications for anthracyclines?

• Breast cancer

• Lymphoma, ALL, AML

• Sarcoma

• Thyroid cancer

• Neuroblastoma

⚠ Major Toxicity: What is the hallmark toxicity of anthracyclines (especially Doxorubicin & Daunorubicin)

Cardiotoxicity (dilated cardiomyopathy)

Cardiac Monitoring

What do you monitor with anthracycline therapy?

LVEF (hold if <40%)Prevention

Prevention

Q: What drug can prevent anthracycline cardiotoxicity?

Dexrazoxane

Other key side effects of anthracyclines?

• Myelosuppression

• Alopecia

• Mucositis

🚫 Contraindications

Contraindications for anthracyclines?

• Pregnancy

• Severe heart failure (LVEF <40%)

• Severe myelosuppression

• Severe hepatic impairment

In which phase of the cell cycle do antifolate antimetabolites act?

Antifolate antimetabolites act in the S phase, where they block DNA synthesis.

Provide the examples Antimetabolites- Antifolates:

1. Methotrexate

2. Permetrexed

3. Pralatrexate

🧠 Mechanism of Action

How do antifolate antimetabolites work?

• Inhibits dihydrofolate reductase (DHFR)

• ↓ folate → ↓ thymidine & purine synthesis

• ↓ DNA & protein synthesis

Primary Indications — Methotrexate

Q: What cancers is methotrexate used to treat?

1. Non-Hodgkin lymphoma,

2. Acute lymphoblastic leukemia (ALL)

3. Other: breast cancer, head and neck cancer, osteosarcoma, and choriocarcinoma.

What non-cancer indications does methotrexate treat?

rheumatoid arthritis and psoriasis as an immunosuppressive therapy

What are the major toxicities associated with methotrexate?

• Mucositis

• Myelosuppression

• Hepatotoxicity

• Nephrotoxicity (high doses)

• Neurotoxicity (high doses)

What medications are used to reduce or rescue methotrexate toxicity?

• Leucovorin (folinic acid) rescue for high-dose MTX

• Folic acid supplementation for chronic low-dose MTX (e.g., RA)

In which patients is methotrexate contraindicated?

• Pregnancy

• Severe hepatic or renal impairment

• Active infection

• Severe myelosuppression

• Patients receiving live vaccines

Which drugs increase methotrexate toxicity by reducing its clearance?

• NSAIDs

• Penicillins

• Probenecid

Name Medications classified as Antimetabolites- Fluoropyrimidines:

1. 5-Fluorouracil (5-FU)

2. Capecitabine (TAS-102)

In which phase of the cell cycle do fluoropyrimidines work?

S phase (they inhibit DNA synthesis)

How does 5-fluorouracil (5-FU) work?

5-FU converts to FdUMP, which inhibits thymidylate synthase (TS) → ↓ thymidine production → impaired DNA synthesis and repair

How does capecitabine relate to 5-FU?

Capecitabine is an oral prodrug of 5-FU, converted to 5-FU in tumor cells

Which cancers are treated with 5-FU?

1. Colorectal cancer

2. Breast cancer

3. Gastric cancer

4. Pancreatic cancer

5. Head & neck cancers

6. Anal cancer

Which cancers are treated with capecitabine?

1. Colorectal cancer

2. Breast cancer

What are the major toxicities of 5-FU and capecitabine?

1. Mucositis

2. Diarrhea

3. Nausea

4. **Myelosuppression

5. Cardiotoxicity (angina-like chest pain — 5-FU)

What are the contraindications for fluoropyrimidines (5-FU, capecitabine)?

• Pregnancy

• Severe myelosuppression

• Severe hepatic impairment

List the main Antimetabolites –
🌱 Deoxycytidine Analogs

1. Cytarabine (Ara-C)

2. Gemcitabine

📍 S-Phase?

1. In which phase do deoxycytidine analogs work?

S phase (block DNA synthesis)

How does cytarabine (Ara-C) work?

Converts to ara-CTP → inhibits DNA polymerase → stops DNA chain elongation

How does gemcitabine work?

Converts to dFdCTP → inhibits DNA synthesis & ribonucleotide reductase (converts RNA to DNA)

Which cancers does cytarabine treat?

AML, ALL, CML blast crisis, lymphoma

Which cancers does gemcitabine treat?

Pancreatic, NSCLC, bladder, ovarian, breast cancers

What are common side effects of deoxycytidine analogs?

• Mucositis

• Nausea

• Myelosuppression

What unique neurologic toxicity does high-dose cytarabine cause?

Cerebellar toxicity (ataxia, dysarthria)

What eye toxicity is associated with cytarabine?

Conjunctivitis (especially high-dose)

What unique side effects are associated with gemcitabine?

Flu-like syndrome, rash

🚫 Contraindications: When should deoxycytidine analogs not be used?

• Pregnancy

• Severe myelosuppression

• Active CNS infection (intrathecal Ara-C)

• Severe hepatic impairment

🌱 Purine Analogs — List Them.

6-Mercaptopurine (6-MP) & 6-Thioguanine (6-TG)

Other: Fludarabine, Cladribine

⚙ Mechanism

How do purine analogs work?

• Incorporate into DNA/RNA → chain termination

• Inhibit purine synthesis & interconversion

• Induce apoptosis

What is 6-mercaptopurine (6-MP) used to treat?

ALL maintenance therapy

What is 6-thioguanine (6-TG) used to treat?

AML

What is fludarabine used to treat?

CLL, low-grade NHL ( non-hodgkins lymphoma) 

What is cladribine used to treat?

Hairy cell leukemia, CLL

⚠ Adverse Effects: What are the major toxicities of purine analogs?

• Myelosuppression

• Hepatotoxicity

• Immunosuppression (especially fludarabine, cladribine)

• **Opportunistic infections (PJP, HSV)

PJP = Pneumocystis jirovecii pneumonia

• A serious fungal pneumonia seen in immunocompromised patients

🚫 Contraindications: When are purine analogs contraindicated?

1. Pregnancy

2. Severe myelosuppression

3. Active infection

4. Live vaccines

Name the Epi-Podo-phyllo-toxins:

etoposide

In which phase does etoposide act?

S phase

⚙ Mechanism: How does etoposide work?

• Inhibits topoisomerase II

• Causes DNA strand breaks

• Prevents religation, leading to cell death

🎯 Indications: Which cancers are treated with etoposide?

1. SCLC (small-cell lung cancer)

2. NSCLC (non-small cell lung cancer)

3. Testicular cancer

4. Lymphoma

5. Gastric cancer

⚠ Adverse Effects: What are common toxicities of etoposide?

1. Myelosuppression

2. Alopecia

3. Hypotension (if IV given too fast)

4. **Secondary AML (t(11;22))

🚫 Contraindications: When should etoposide be avoided?

• Pregnancy

• Severe myelosuppression

• Severe hepatic impairment

Name the Camptothecins

Irinotecan, Topotecan, Liposomal Irinotecan

🌱 Cell-Cycle Phase: In which phase do camptothecins work?

S phase (DNA synthesis phase)

⚙ Mechanism: How do camptothecins work?

• Inhibit topoisomerase I

• Prevent DNA religation

• Cause DNA strand breaks → cell death

🎯 Indications: What does irinotecan treat?

• Metastatic colorectal cancer

• Gastric cancer

• SCLC

What does topotecan treat?

• SCLC

• Ovarian cancer

What does liposomal irinotecan treat?

Pancreatic cancer (post-gemcitabine

⚠ Adverse Effects: What are common toxicities of camptothecins?

• Nausea & diarrhea

• Myelosuppression

• Alopecia

🚫 Contraindications: When should camptothecins be avoided?

1. Pregnancy

2. Severe myelosuppression

3. Bowel obstruction (irinotecan)

4. Severe diarrhea history

Name the 1 antitumor abx.

Bleomycin

Cell-Cycle Phase: In which phase does Bleomycin work?

G2 phase

⚙ Mechanism of Action: How does Bleomycin work?

Generates free radicals → causes DNA strand breaks → cell death

🎯 Indications: Which cancers are treated with Bleomycin?

• Hodgkin lymphoma

• Testicular cancer

• Squamous cell cancers

What non-cancer use does Bleomycin have?

Pleurodesis for malignant pleural effusions

⚠ Adverse Effects: What is the most serious toxicity of Bleomycin?

Pulmonary fibrosis (dose-limiting)
Memory: Bleo = Blow (lungs)

What other side effects can occur with Bleomycin?

• Fever

• Rash, Hyperpigmentation

• Raynaud’s phenomenon

• Anaphylaxis

Raynaud’s phenomenon = a condition where the blood vessels in fingers/toes spasm in response to cold or stress → causing color changes + pain.

🚫 Contraindications: Who should not receive Bleomycin?

• Pregnant patients

• **Patients with pulmonary disease

What are the 2 M Phase medications?

Vinca Alkaloids: Vincristine, Vinblastine, Vinorelbine
Taxanes: Paclitaxel, nab-Paclitaxel, Docetaxel, Cabazitaxel

Name the Vinca Alkaloids

1. Vincristine

2. Vinblastine

3. Vinorelbine

In which phase do vinca alkaloids act?

M phase (block mitosis)

⚙Mechanism: How do vinca alkaloids work?

They bind tubulin and inhibit microtubule assembly, causing mitotic arrest at metaphase.

Memory: Vinca = "Stop the spindles!" 🧵🚫

Which cancers are treated with vincristine?

1. ALL

2. Hodgkin & non-Hodgkin lymphoma

3. Wilms tumor (*kidney tumor in children)

4. Rhabdomyosarcoma (*muscle tissue tumor)