snack time pt. 2

what occurs in metaphase

nucleus dissolves, chromosomes align in center

cell cycle consists of

M phase and interphase

interphase G0

resting, not preparing to divide

interphase G1

cell growth, organelle synthesis, checkpoint control (Rb, p53)

interphase S phase:

DNA replication + histone synthesis (shanar replicates these hoes)

interphase G2

final growth, organelle replication, prep for mitosis

M checkpoint?

spindle check point; happens to ensure all chromosomes are properly attached to spindle fibers at their kinetochores and aligned at the metaphase plate before sister chromatids separate

Radiation therapy does what to dna and when

breaks dna strands; most susceptible in G2 and M phases

what type of tissue is most affected by radiation?

lymphoid

which chemotherapy drug causes mucositis, xerostomia?

methotrexate

why are many anticancer drugs teratogenic?

they target rapidly dividing cells, which includes fetal cells during development, causing congenital malformations or fetal death if given during pregnancy

teratogenic def

causing developmental abnormalities or birth defects in embryo/fetus

what is tumor lysis syndrome (TLS)

metabolic disturbance from rapid tumor cell death causing hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia

what are alkylating agents in chemotherapy?

drugs that add alkyl groups to DNA, causing cross-linking, strand breaks, and inhibition of replication

give 2 examples of alkylating agents

cisplatin and cyclophosphamide

major toxicity of cisplatin?

nephrotoxicity and ototoxicity

major toxicity of cyclophosphamide?

hemorrhagic cystitis

what drug class is methotrexate?

antimetabolite

MOA of methotrexate?

inhibits dihydrofolate reductase, blocking conversion of dihydrofolate to tetrahydrofolate → decreased thymidylate and purine synthesis → impaired DNA synthesis

which antitumor antibioitcs inhibit topoisomerase II?

doxorubicin, daunorubicin, etoposide, teniposide

MOA of topoisomerase II inhibitors?

prevent the re-ligation of double stranded DNA breaks by stabilizing the topoisomerase II-DNA complex

major toxicity of doxorubicin/daunorubicin (topoisomerase II inhibitors)

cardiac

major toxicity of etoposide and teniposide (topoisomerase II inhibitors)

myelosuppression, alopecia, GI upset

what drug class do vinca alkaloids belong to?

antimicrotubule agents

MOA of vinca alkaloids?

bind to beta-tubulin and inhibits microtubule assembly, preventing spindle formation and arresting the cell in metaphase

give 2 examples of vinca alkaloids

vincristine and vinblastine

major toxicity of vincristine?

neurotoxicity (peripheral neuropathy)

major toxicity of vinblastine?

bone marrow suppression

phases of cancer treatment

induction, consolidation, maintenance, remission

induction phase in cancer tx?

initial high-intensity therapy aimed at rapidly reducing tumor burden and inducing remission

what is consolidation phase in cancer tx?

additional tx given after remission to eliminate residual microscopic disease and prevent relapse

maintenance phase in cancer tx?

long term, lower intensity therapy to maintain remission and prevent recurrence

remission phase?

disappearance of signs and symptoms of cancer - can be complete or partial

which is true regarding chronic leukemia

a. They progress rapidly
b. Have shorter, more devastating clinical course than acute
c. Characterized by proliferations of lymphoid or hematopoietic cells that are more mature than those of acute
d. Constitute 75% of all leukemias

characterized by proliferations of lymphoid or hematopoietic cells that are more mature than those of acute

how do acute and chronic leukemias differ in cell maturity and disease course?

acute: immature precursor cells (blasts) released prematurely, rapid onset, aggressive course

chronic: cells have partial maturity, slower progression, often diagnosed incidentally during blood test

small pinpoint hemorrhages that occur on skin are

petechiae

common signs of thrombocytopenia

bleeding,

petechiae,

purpura,

ecchymosis (large bruises)

skin hemorrhages often become purple

petechiae vs purpura

petechiae <2mm

purpura >3mm

same except for size

Why might a patient diagnosed with acute lymphoblastic leukemia (ALL) 5 years ago receive a third-generation cephalosporin for an infection?

these pts may have long-term residual immune compromise making them more susceptible to bacterial infections.

third-gen cephalosporins provide broad-spectrum coverage, esp against gram negative pathogens that can cause life threatening infections in immunocompromised individuals

third gen cephalosporins can be used for

gram neg or positive

penicillin is what type of antibiotic and moa?

beta-lactam; binds to and inactivates penicillin-binding proteins (PBPs) which are enzymes bacteria need to build their cell walls

whats beta-lactamase (penicillinase)

a bacterial defense enzyme that breaks the beta-lactam ring in regular penicillin, inactivating the drug. this is why many bacteria, especially staphylococcus aureus, are resistant to penicillin (able to infect us despite taking the drug)

scientists made penicillinase-resistant penicillins such as

methicillin, nafcillin, oxacillin

how do penicillinase-resistant penicillin (methicilin, nafcillin, oxacillin) work?

by chemically modifying the side chains so the beta-lactamase enzyme in bacteria cannot bind and break them.

this means these drugs can still kill bacteria that produce beta-lactamase- but theyre not immune to all forms of resistance. (ex: MRSA has altered PBPs so the drug can’t bind)

(basically

regular penicllin = beta lactamase breaks it

methicillin-type penicillin = beta lactamase cannot touch it)

which of the following antibiotics works by inhibiting cell wall synthesis?

tralosporin