-Nitrogen mustards

(cyclophosphamide, mechlorethamine, ifosfamide). Related to phosgene and 1st IV chemotherapy, Prodrug administered in an inactive form

-used to treat cancers (leukemias, lymphomas, solid tumors)

-used as immuno ablative (small and medium vessel vasculitis conditions)

-Progressive or refractory systemic lupus erythematosus (autoimmune disease)

-Adverse effects (Depress bone marrow fxn, leukemia or other malignancies, hair loss, GI disturbances, Infertility, teratogenic)

-May also cause water retention, bladder cancer or hemorrhagic cystitis

-Drugs include Carmustine and Lomustine

-Require activation of cytochrome P450 and are highly lipid soluble (cross blood brain barrier)

-Can treat brain tumors (e.g. glioblastomas)

-Adverse effects (neurotoxicity, seizures, ataxia)

-Interphase (G1, S and G2) is where cell is preparing for division. S phase is where DNA is replicated (where the 46 chromosomes are duplicated) so that each daughter cell can have own copy of genetic material

-Mitosis is phase where cell actively divides

-DNA has 2 strains (double helix) composed of DNA nucleotides (building blocks of nucleic acids) including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)

-broken into 5 carbon sugar, phosphate group and a nitrogenous base ("nucleobase")

-5 carbon sugar is either deoxyribose (DNA) or ribose (RNA)

-Nuclear bases can be either 3 pyrimidines (cytosine, thymine (DNA) or Uracil (RNA)) or 2 purines (Adenine and Guanine)

-DNA nucleotides are made by RNA nucleotides

-Ribonucleotide reductase reduces RNA into DNA

-Cancer cells replicate DNA all the time and require more deoxyribonucleotide for the process and makes them more sensitive to ribonucleotide reductase inhibitors since they decrease the amount of deoxyribonucleotides

-Ribonucleotide reductase inhibitors act in the S phase and are cell cycle-specific are normal tissues that divide rapidly like bone marrow and hair follicles which explains why these medications are more toxic to these tissues

-Hydroxyurea, Fludarabine phosphate, and gemcitabine

-Hydroxyurea is used to treat myeloproliferative disorders and sickle cell disease

-Fludarabine phosphate inhibits DNA polymerase and is used to treat leukemias

-Gemcitabine is used to treat carcinomas and non-Hodgkin's lymphoma

-Side effects include severe myelosuppression, GI disturbances, pneumonitis, and mild skin reactions, and minimal teratogenic effects

-Block an enzyme called topoisomerase

-used as anticancer agents and target specific phases of the cell cycle (late S and early G2 phases)

-interesting fact (derived from natural products such as trees and plants)

-Drugs include Camptothecins, Podophyllotoxins

-during DNA replication DNA helicase is used to unzip the double helix which results in a replication fork- the helix ahead of it starts to 'overwind' which can slow down the replication

-DNA topoisomerase works ahead of this overwinding to loosen up tight DNA coils

-Topoisomerase 1 cuts 1 strand during DNA replication

-Topoisomerase 2 cuts both strands

-Side effects include myelosuppression, alopecia and GI problems (fewer toxicities than most other anticancer agents)

-used to treat cancer

-disrupt guanine bases of DNA and can affect all phases of the cell cycle

-inhibits DNA repair and prevents DNA separation for replication

-Platins are cell cycle nonspecific agents. Act like DNA alkylating medications (but do not have an alkyl group)

-Drugs include Cisplatin, Carboplatin, Oxaliplatin which are all administered via IV and eliminated through the kidneys

-Cisplatin and Carboplatin are used to treat variety of solid tumors and osteosarcoma

-Side effects include GI problems, nephrotoxicity (related to ROS production), neurotoxicity/ototoxicity (tinnitus and hearing loss), allergic reactions and mild bone marrow suppression

-Anti-cancer drugs in this class include Vinca alkaloids and taxanes (these drugs are both given IV)

-Vinca alkaloids (e.g. Vinblastine and Vincristine) bind to B-tubulin and block formation into protofilaments and the cell cannot form stable mitotic spindles. Disrupt mitosis in ALL RAPIDLY DIVIDING CELLS IN BODY (e.g. hair follicles and GI epithelium) and bone marrow suppression, and neurotoxicity.

-Taxanes (Paclitaxel and Docetaxel) also act on microtubules but they over stabilize microtubules and prevents break down in anaphase so the cell cannot divide

-Cytoskeleton of the cell is a network of proteins that give the cell its shape and provide a dynamic network (to allow it to change shape, move, divide, contract and pull in/out molecules)

-Cytoskeleton is composed of 3 components (Actin filaments, Intermediate filaments and microtubules)

-Microtubules are composed of alpha-tubulin and B-tubulin that form protofilaments (13 of the protofilaments come together to form a single microtubule)

-Microtubules play a central role in cell division, during cell division there are 2 centrosomes inside the cell and each centrosome is made of 2 centrioles. Each centriole is made of 9 sets of microtubule triplets

-Mitosis is divided into 4 phases (prophase, metaphase, anaphase, telophase)

-Cancer cells replicate rapidly and are constantly undergoing mitosis and microtubules are always at work. Therefore, microtubule inhibitors will affect cancer cells more than our healthy cells (which only divide occasionally)

-Interfering with the formation of microtubules causes mitosis to fail and the cell will eventually die without replicating

-Used for treatment of various conditions including cancer, infections, and autoimmune disorders

-During the S phase of the cell cycle, DNA replication occurs

-Cancer cells divide all day long so they are very sensitive to cytotoxic medications that block DNA synthesis

-Antimetabolites mimic nucleobases or folic acid and cause DNA synthesis to come to a stop

-Drugs that inhibit Purine (Azathioprine and Cladribine)

-Drugs that inhibit Pyrimidine (Cytarabine and 5-Fluorouracil)

-Drugs that are folic acid analogs (Methotrexate)

-DRUG INTERACTION may be possible if Azathioprine (pro-drug of 6-mercaptopurine or 6-MP) is given with Allopurinol (inhibits xanthine oxidase). Xanthine oxidase is an enzyme that metabolizes 6-MP. When Azathioprine and Allopurinol are given together 6-MP increases to toxic levels

-5-Fluorouracil (5-FU) is a pyrimidine analog that interferes with the folic acid cycle. Indicated for solid tumors

-Methotrexate is a folic acid analog. Methotrexate decreases synthesis of DNA, RNA and proteins- inhibiting cell division