lecture 10: topoisomerase, microtubule, antibiotics and cytokines

MG: infectious diseases and oncology

name a topoisomerase I inhibitor

irinotecan

irinotecan (group-MOA-Resistance-SE-Indication)

Topoisomerase I inhibitors (= cut one strand in the unknotting or unlinking of DNA)

·      MOA: activated by hydrolysis, inhibit topoisomerase I – inhibit transcription and replication.

·      Resistance: MDR receptor

·      SE: cholinergic syndrome (high ACh levels), GI symptoms, bone marrow suppression.

·      Indications: colon cancer

name 3 topoisomerase II inhibitors

doxorubicin, daunorubicin and epirubicin

doxorubicin, daunorubicin and epirubicin (group-MOA-SE-Indication)

Topoisomerase II inhibitors (=cut both strands in the unknotting or unlinking of DNA)

·      MOA: inhibit topoisomerase II – DNA double strand breaks – intercalation into DNA.

·      SE: cardiotoxicity, myelotoxicity and GI symptoms.

·      Indications: solid tumors, hematologic malignancies.

name three types of vinca alkaloids drugs (which group?)

·      Vincristin, vinblastin, vinorelbin. = anti-microtubule drugs

Vincristin, vinblastin, vinorelbin. (group-MOA-PK-SE-Indication)

Anti-microtubule drugs

Vinca alkaloids

·      MOA: inhibit tubulin polymerization – no microtubule assembly – stop cell division

·      PK: CYP450 metabolism, metabolism in hepatobiliary system

·      SE: vomiting, neurotoxicity, bone marrow suppression, hyperuricemia.

·      Indications: acute lymphoblastic leukemia (ALL), lymphomas.

name 3 type of taxane drugs (which group?)

paclitaxel, docetaxel and cabazitaxel (anti-microtubule drugs)

paclitaxel, docetaxel and cabazitaxel (group-MOA-PK-SE)

Taxanes: - anti-microtubule drugs

·      MOA: high binding affinity to microtubules - ­­tubulin polymerization – inhibit mitosis

·      Resistance: Cabazitaxel only used in resistant cases

·      PK: CYP metabolized, excreted via hepatobiliary route

·      SE: paclitaxel – acute hypersensitive reactions – preventive anti-histamine and steroid treatment

·      Ind: broad range of solid tumors

name a type of antibiotic which can be used during chemotherapy

bleomycin

bleomycin (group- MOA- SE- PK- Indication 2)

Antibiotics

·      MOA: small peptide containing DNA-binding regions and an iron-binding domain, leading to single- & double-strand breaks – free radical formation – inhibition of DNA synthesis (G2 specific).

·      SE: pulmonary toxicity, pneumonitis with cough.

·      PK: kidney excretion

·      Indication: Hodgkin’s and non-Hodgkin’s lymphomas.

name two types of cytokine subgroups

interferons and interleukins

name a type of interferon drug

interferon a

interferon a (group0 MOA- SE)

Cytokines

Interferons

·      MOA: activation of transcription factor (JAK-STAT pathway) – change in IF gene expression.

·      SE: flu-like symptoms, CNS, myelosuppression, kidney- and cardiotoxicity.

name a type of interleukine

aldesleukin

aldesleukin (group- MOA- indication- SE(3))

Interleukins - cytokines

·      MOA: promoting proliferation, differentiation & recruitment of T and B cells. Stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL).

·      Indication: metastatic renal cell carcinoma

·      SE: flu-like, AP, GI symptoms