28 - anti-cancer drugs

d. Amifostine

1. Rescue therapy for cisplatin toxicity

   a. Dexrazoxane

   b. Mesna

   c. Folinic acid

   d. Amifostine

a. Paclitaxel

2. An anti-cancer drug that is obtained from pacific yew tree

   a. Paclitaxel

   b. Vincristine

   c. Reserpine

   d. Camptothecin

3. Rescue therapy for cyclophosphamide toxicity

   a. Mesna

   b. Acrolein

   c. Folinic acid

   d. Dexrazoxane

b. Propenal

4. The toxic metabolite after metabolism of cyclophosphamide

   a. Mesna

   b. Propenal

   c. Propanal

   d. 1-propanol

a. it blocks the M-phase of the cell cycle

5. MOA of vincristine

   a. it blocks the M-phase of the cell cycle

   b. it blocks the G0 phase of the cell cycle

   c. it blocks the S phase of the cell cycle

   it blocks ALL THE phases of the cell cycle

Cancer

Uncontrolled growth of tumor cell in a part of the body

Cure, Palliative Care

Goal for Cancer:

G0

• Cell cycle

• Quiescent Phase

• Resting Phase

G1

• Cell cycle

• need to produce enzymes,

• needed for DNA synthestis

S (Synthesis Phase)

• Cell cycle

• DNA synthesis

• Folate antagonist, Purine & Pyrimidine analogs

• Cell Cycle Specific

G2 (Pre-Mitotic Phase)

• Cell cycle

• Makes cellular components

• Bleomycin

• Cell Cycle Specific

M (Mitotic Phase)

• Cell cycle

• Cell division

• Vinblastine, Vincristine, Taxanes

• Cell Cycle Specific

• Alkylating agents

• Antibiotics

• Nitrosourea

Non-Cell Cycle Specific:

Alkylating Agents

• MOA: N7 Guanine Alkylation

• Largest group

• Cross Linking: affects transcription

• Mispairing of Bases: produced defective protein

• Depuriation: cleavage of DNA strand

Alkylating Agents effects:

• Nitrogen Mustard

• Nitrosoureas

• Alkyl sulfonates

• Ethyleneimines

• Triazenes

Alkylating Agents:

• Cyclophosphamide

• Mechlorethamine

• Chlorambucil

Ex of Nitrogen Mustard drugs:

Cyclophosphamide

• Phosphoramide mustard

• Tx: ovarian, breast cancer

Acrolein

Toxic constituent of Cyclophosphamide:

Mechlorethamine

1st line of alkylating agent

Chlorambucil

1st line tx for Chronic lymphocytic leukemia (CLL)

Carmustine, Lomustine, Semustine

• Nitrosoureas; Alkylating agent

• Highly Lipophilic

Streptozocin

Tx for pancreatic cancer / insulinoma

• Breast enlargement = Glynecomastia

• Black skin = Skin Pigmention

• Busulfan lung = Pulmonary Fibrosis

Busulfan A/E:

Ethyleneimines

Largely replaced by cyclophosphamide

Dacarbazine

Tx for Metastatic melanoma

inhibit S –Phase

Anti-metabolites’ MOA:

• Folate antagonists (Methotrexate, Pemetrexed & Pralatrexate)

• Purine Analogs (Mercaptopurine)

• Pyrimidine Analogs (Fluorouracil, Cytarabine)

Anti-metabolites:

Methotrexate

• MOA: (-) Dihydrofolate Reductase Enzyme

• A/E: N/V, Diarrhea, stomatitis

• Rescue: Leucovorin (folinic acid)

Mercaptopurine

• Azathioprine → 6-MP

• D/I: + Allupurinol

Fluorouracil (5 -FU

• MOA: (-) Thymidylate Synthetase Enzyme

• Use: Basal Cell Carcinoma, Colorectal Cancer

• Methotrexate

• Pemetrexed & Pralatrexate

Anti-metabolites; Folate antagonists:

• Fluorouracil (5 -FU)

• Cytarabine

Anti-metabolites; Pyrimidine antagonists:

• Mercaptopurine

• Thioguanine, Fludarabine, Cladribine, Pentostatin

Anti-metabolites; Purine Analogs:

• Anthracyclines

• Bleomycin

• Mitomycin

• Plicamycin

Antibiotics:

Doxurubicin, Daunorubicin, Idarubicin, Epirubicin, Mitoxantrone

• MOA: Interacts w/ O2

• Toxicity: Delay CHF

• Rescue: Dextrazoxane

Bleomycin

• MOA: can cause DNA breakage via oxidative mechanism

• Toxicity: *Pulmonary Fibrosis, Alopecia, Hyperpigmentation

• Vinca Alkaloids

• Taxanes

• Epipodophyllotoxins

• Camptothecin Analogs

Plant-derived products for cancer:

Periwinkle

Source of Vinca Alkaloids:

Vinca Alkaloids

• MOA: (-) Tubular Polymerization

• A/E: Peripheral neuropathy, constipation, bone marrow suppression (VBL)

Vincristine, Vinblastine, Vinorelbine

Example of Vinca Alkaloids:

Taxanes

• MOA: (+) Tubular Polymerization

• A/E: Serious hypersensitivity (Mx: pretreated w/ dexamethasone & Dipenhydramine)

Pacific Yew Tree

Taxanes Source:

Paclitaxel, Docetaxel

Example of Taxanes:

Epipodophyllotoxins

• MOA: (-) Tubular Topoisomerase II

• Etoposide, Teniposide (For Testical Cancer)

Mayapple

Epipodophyllotoxins Source:

Camptothecin Analogs

• MOA: decrease tubular topoisomerase

  • Natural (Camptothecin)

  • Synthetics

    • Irinotecan (Tx for Colorectal Cancer) |A/E: Diarrhea

    • Topotecan

Camptotheca Tree

Camptothecin Analogs Source:

Irinotecan

Tx for Colorectal Cancer

L –Asparaginase

An enzyme that catalyzes asparagine to Aspartic acid & Ammonia

hypersensitivity

L –Asparaginase A/E:

E.coli, E.carotovora

L –Asparaginase Source:

less likely to cause allergic reaction

Pegaspargase A/E:

• Cisplatin

• Carboplatin

• Oxaliplatin

Platinum Coordination Complexes Agents:

Cisplatin

• MOA: same as alkylating agents

• Toxicity: Persistent Vomiting, Ototoxicity, Nephrotoxicity (Mx: *Amifostine, Mannitol w/ forced hydration)

Nephrotoxicity

Cisplatin Toxicity:

cold induced peripheral neuritis (Mx. Doluxetin)

Oxaliplatin A/E:

Tamoxifen

A hormone used to tx breast cancer

Finasteride

A hormone used to tx for BPH, dec risk of prostate cancer

Flutamide

A hormone used to tx for prostate cancer

Buserelin & Leuprolide

A hormone used to tx for Endometriosis, prostate cancer

Octreotide

A hormone used to tx for carcinoid tumor

Rituximab

1st anti-CA monoclinical antibodies

Bevacizumab

1st line for colorectal cancer

• Imatinib, Dasatinib

• Erlotinib, Gefitinib

• Surafenib, Sunitinib

Tyrosine Kinase Inhibitors:

Imatinib, Dasatinib

• Targets BCR - ABL TYROSINE KINASE

• Tx for Chronic myelogenous leukemia

Erlotinib, Gefitinib

• Targets Epidermal GF Receptor Tyrosine Kinase

• expressed as lung cancer cell

Surafenib, Sunitinib

• Targets vascular endothelial GF RECEPTOR, renal cance