Term
| What are the 4 principles of giving Drug Combinations? |
|
Definition
| 1) Each drug should be active alone, 2) The drugs should have Different Mechanisms, 3) The drugs should have Different Toxicities, 4) Cross-resistance should be minimal |
|
|
Term
| What are Cell Cycle Specific Drugs? |
|
Definition
| Drugs only active in specific cell cycle phases |
|
|
Term
| What are Cell Cycle Non-specific drugs? |
|
Definition
| Drugs that target both resting and dividing cells and so are cytotoxic throughout the cell cycle |
|
|
Term
| What is the general mechanism of Alkylating Agents and what is their cell cylce activity? |
|
Definition
| Cell Cycle Non-specific agents that cross-link DNA during all phases of the cell cycle to damage the DNA |
|
|
Term
| What does the Crosslinking of DNA interfere with? |
|
Definition
|
|
Term
| What are the 4 types of Alkylating Agents? |
|
Definition
| Nitrogen mustards, Nitrosoureas, Alkyl Sulfonate, Platinum Complexes |
|
|
Term
| What are the three main Nitrogen Mustards? |
|
Definition
| Mechlorethamine, Cyclophosphamide, Ifosfamide |
|
|
Term
| What are the 2 main Nitrosoureas? |
|
Definition
|
|
Term
| What is the main Alkyl sulfonate? |
|
Definition
|
|
Term
| What is the main Platinum Complex? |
|
Definition
|
|
Term
| What is the most reactive of the nitrogen mustards, and what does it treat? |
|
Definition
| Mechlorethamine; treats Hodgkin's lymphoma + many others |
|
|
Term
| How is Mechlorethamine administered? |
|
Definition
| IV immediately b/c it is unstable |
|
|
Term
| Toxicology of Mechlorethamine |
|
Definition
|
|
Term
| Cyclophosphamide is highly effective vs what cancer? |
|
Definition
|
|
Term
| How is Cyclophosphamide administered and how does it become activated? |
|
Definition
| Orally; it is a Prodrug converted via CP450 |
|
|
Term
| Toxicity of Cyclophosphamide |
|
Definition
| Cardiotoxic, Hemorrhagic cystitis, Hematuria (bloody urine + bladder burn) |
|
|
Term
| What toxic breakdown product of Cyclophosphamide contributes to Hemorrhagic cystitis, bladder burn, and hematuria, and how is it reduced (inactivated to reduce effects)? |
|
Definition
| Acrolein; MESNA is given to reduce levels and prevent hemorrhagic cystitis |
|
|
Term
| How is Ifosfamide administered and activated? |
|
Definition
| IV with MESNA; activated via P450 |
|
|
Term
|
Definition
| Neurotoxic, Nephrotoxic, Hemorrhagic Cystitis, Hematuria |
|
|
Term
| What are the two Nitrosoureas Carmustine and Lomustine effective against and what is their mechanism? |
|
Definition
| Astrocytomas and Metastatic brain tumors; they Inhibit DNA, RNA, and protein Synth |
|
|
Term
| How is Carmustine administered? Lomustine? |
|
Definition
| Carmustine via IV; Lomustine orally |
|
|
Term
| Toxicity of Carmustine and Lomustine |
|
Definition
| Pulmonary Fibrosis, BM suppression |
|
|
Term
| What is the Alkyl sulfonate Busulfan used against? |
|
Definition
| Chronic Myelogenous Leukemia (CML) |
|
|
Term
|
Definition
|
|
Term
| What is the mechanism of the platinum complex Cisplatin? |
|
Definition
| Covalently crosslinks GG base pairs by bending DNA |
|
|
Term
| What is Cisplatin effective against (when combined with other particular drugs)? |
|
Definition
|
|
Term
|
Definition
| Renal Damage, Ototoxic, Peripheral sensory Neuropathy |
|
|
Term
| How do Antimetabolites work, what phase are they active in, and what types of tumors are they most effective in treating? |
|
Definition
| They are structural analogs of normal molecules; S-phase specific, and they are most effective on rapidly proliferating tumors (leukemias and lymphomas) |
|
|
Term
| What are the 5 Antimetabolites? |
|
Definition
| Methotrexate, Mercaptopurine, Fluorouracil, Capecitabine, Cytarabine |
|
|
Term
| Methotrexate, the most widely used Antimetabolite is most effective at treating what two cancers? |
|
Definition
| Pediatric Acute Lymphoblastic Leukemia (ALL), and Choriocarcinoma |
|
|
Term
| What is the mechanism of Methotrexate? |
|
Definition
| analog of Folic acid, it inhibits Dihydrofolate Reductase to block dTMP synthesis from dUMP (and thus, inhibits DNA synthesis) |
|
|
Term
| What is the role of Dihydrofolate Reductase? |
|
Definition
| Methylates Dihydrofolate to form THF |
|
|
Term
| What is the Toxicity of Methotrexate? |
|
Definition
| Hepatic Necrosis, BM suppression |
|
|
Term
| What can be given in case of Methotrexate toxicity? |
|
Definition
|
|
Term
| What is the Mechanism of Fluorouracil? |
|
Definition
| Mimics Uracil and thus inhibits synthesis of Thymidine from Uracil via Thymidilate Synthase |
|
|
Term
| What is the Toxicity of Fluorouracil and how is it administered? |
|
Definition
| Severe Ulceration of oral and GI mucosa and thus it is given IV |
|
|
Term
| What drug potentiates the action of Fluorouracil? |
|
Definition
|
|
Term
| What is the pharmacological activity of Capecitabine? |
|
Definition
| It is a prodrug of Fluorouracil |
|
|
Term
| What is Mercaptopurine used to treat and in what manner? |
|
Definition
| Maintenance therapy for Acute Lymphoblastic Leukemia (ALL) |
|
|
Term
| What is the mechanism of Mercaptopurine? |
|
Definition
| Inhibits Guanine (purine) synthesis |
|
|
Term
| What is the toxicity of Mercaptopurine? |
|
Definition
|
|
Term
| What is Cytarabine used to treat? |
|
Definition
|
|
Term
| What is the mechanism of Cytarabine? |
|
Definition
| It is a Cytosine analog that inhibits DNA chain elongation |
|
|
Term
| What is the toxicity of Cytarabine? |
|
Definition
|
|
Term
| What are the 4 antibotics that are Chemotherapeutic Drugs? |
|
Definition
| Doxorubicin, Epirubicin, Dactinomycin, Bleomycin |
|
|
Term
| What is the mechanism of action of Doxorubicin? |
|
Definition
| Doxorubicin docks onto the nicked ends of Topoisomerase II to prevent replication |
|
|
Term
| What are the Toxicities of Doxorubicin? |
|
Definition
| Red urine (color, not blood hence -rubicin), Severe local tissue damage with extravasation, Cardiac Toxicity, BM suppression |
|
|
Term
| How does Doxorubicin cause cardiac damage (mechanism)? |
|
Definition
| Doxorubicin interacts with Fe to generate Hydroxyl radicals that damage myocytes |
|
|
Term
| What is the pharmacology of Epirubicin? |
|
Definition
| It is an Analog of Doxorubicin |
|
|
Term
|
Definition
| same as Doxorubicin: Red urine, Local tissue damage, BM depression, Cardiac Toxicity |
|
|
Term
| What H2 receptor antagonist used in ulcer therapy will increase the levels of Epirubicin and should be avoided? |
|
Definition
|
|
Term
| What is Dactinomycin used to treat? |
|
Definition
| pediatric Rhabdomyosarcoma and Wilm's tumor |
|
|
Term
| What is the mechanism of action of Dactinomycin? |
|
Definition
| Intercalates between G-C base pairs in DNA to inhibit RNA polymerase and Topoisomerase II |
|
|
Term
| What is the toxicity of Dactinomycin? |
|
Definition
| Severe Local tissue damage and necrosis with extravasation |
|
|
Term
| What is the mechanism of Bleomycin (4 steps)? |
|
Definition
| 1) DNA-Bleomycin-Fe complex forms, 2) DNA-bleomycin-Fe interacts with O2, 3) Superoxide and hydroxyl radicals form, 4) The radicals Fragment DNA |
|
|
Term
| What are the Toxicities of Bleomycin? |
|
Definition
| Mild BM depression, Pulmonary Fibrosis |
|
|
Term
| Why does Bleomycin cause Pulmonary Fibrosis? |
|
Definition
| Bleomycin is degraded by Hydrolase, which is found only in low levels in the lungs |
|
|
Term
| Of the antibiotics, which is the only one that is cell cycle specific and in which phase is it active? |
|
Definition
|
|
Term
| What are the 4 drugs derived from Plants that are Chemotherapeutic drugs? |
|
Definition
| Vincristine, Vinblastine, Paclitaxel, and Etoposide |
|
|
Term
| What is Vincristine used to treat? |
|
Definition
| Pediatric Leukemia and Adult Lymphomas |
|
|
Term
| What is Vinblastine used to treat? |
|
Definition
|
|
Term
| What is the mechanism of Vincristine and Vinblastine? |
|
Definition
| They bind to Tubulin and inhibit their polymerization into microtubules (and are thus mitotic inhibitors) |
|
|
Term
|
Definition
| Mild BM, Sensory neuropathy |
|
|
Term
|
Definition
| More BM toxic than Vincristine, Less neurotoxic than Vincristine |
|
|
Term
| *What are the only two chemotherapeutic druts that have Mild BM depression? |
|
Definition
| Bleomycin and Vincristine |
|
|
Term
| What is the indication for using Paclitaxel and Docetaxel? |
|
Definition
| To treat Cisplatin-Resistant Tumors |
|
|
Term
| What is the mechanism of Paclitaxel and Docetaxel? |
|
Definition
| Feezes polymerized microtubules to block mitosis in metaphase |
|
|
Term
| What is the toxicity of Paclitaxel and Docetaxel? |
|
Definition
| Peripheral sensory Neuropathy |
|
|
Term
| What is the mechanism of Etoposide? |
|
Definition
| Inhibition of Topoisomerase II |
|
|
Term
| What are the 4 drugs that inhibit DNA Topoisomerase II? |
|
Definition
| Doxorubicin, Epirubicin, Dactinomycin, Etoposide |
|
|
Term
|
Definition
| BM depression and Peripheral Neuropathy |
|
|
Term
| What are the 4 drugs that have Peripheral Sensory Neurotoxicity? |
|
Definition
| Cisplatin (alkylating agent), Vincristine (plant), Paclitaxel (plant), and Etoposide (plant) |
|
|
Term
| What are Horomone Inhibitors used to treat and what benefit do they have as Chemotherapeutic agents? |
|
Definition
| They act on Breast and Prostate tumors (which usually require estrogen/androgen for growth) and they have the benefit of having minor side effects |
|
|
Term
| What are the Two classes and their subclasses of Hormone/Receptor Inhibitors? |
|
Definition
| Hormone Inhibitors: Aromatase inhibitors - Receptor Tyrosine Kinase Inhibitors: Chemical agents and Monoclonal antibodies |
|
|
Term
| What are the three Aromatase Inhibitors? |
|
Definition
| Exemestane, Letrozole, Anastrozole |
|
|
Term
| What is the mechanism of the Aromatase inhibitors and what cancer in particular do they treat? |
|
Definition
| They block the conversion of Androgen to Estrogen, reducing Estrogen levels to treat breast cancer |
|
|
Term
| What are the two main Receptor Tyrosine Kinase Inhibitors that are Chemical Agents? |
|
Definition
|
|
Term
| What is the main therapeutic use of Tamoxifen? |
|
Definition
| Estrogen-dependent Breast Cancer |
|
|
Term
| What beneficial side effect does Tamoxifen hve? |
|
Definition
| It acts as an agonist of the estrogen receptor in some tissues to reduce serum cholesterol and prevent bone loss |
|
|
Term
| Mechanism of Imatinib and what cancer it is used for |
|
Definition
| Inhibits BCR-Abl tyrosine kinase in CML |
|
|
Term
| What are the three Receptor Tyrosine Kinase Inhibitors that are Monoclonal Antibodies? |
|
Definition
| Trastuzumab, Cetuximab, and Bevacizumab |
|
|
Term
| What is the mechanism of Trastuzumab and what cancer does it target? |
|
Definition
| Inhibits HER2 (Human Epidermal growth factor Receptor 2) in Metastatic Breast Cancer |
|
|
Term
| What is the toxicity of Trastuzumab? |
|
Definition
| Cardiomyopathy, infusion reaction |
|
|
Term
| What is the mechanism of Cetuximab |
|
Definition
| Monoclonal antibody that binds to/inhibits EGFR and HER1 to inhibit growth and cause apoptosis |
|
|
Term
| What is the target of Cetuximab? |
|
Definition
| Metastatic Colorectal Cancer |
|
|
Term
| What is the toxicity of Cetuximab? |
|
Definition
| Severe infusion reaction (airway obstruction and hypotension) |
|
|
Term
| What is the mechanism of Bevacizumab? |
|
Definition
| Monoclonal antibody that binds to Vascular Endothelial Growth Factor (VEGF) to inhibit angiogenesis |
|
|
Term
| What is the target of Bevacizumab? |
|
Definition
| Metastatic Colorectal Cancer |
|
|
Term
| What is the toxicity of Bevacizumab? |
|
Definition
| Hypertension, Proteinuria, and Congestive Heart Failure |
|
|
