Cytotoxic Chemotherapy Lecture Notes

A comprehensive set of vocabulary flashcards covering cytotoxic drug classes, mechanisms of action, specific drug examples, and metabolic pathways as discussed in the lecture notes.

Cytotoxic Chemotherapy

A form of cancer chemotherapy that aims to induce apoptosis or senescence ($G0$ phase) by targeting cell division, including $DNA$ replication, transcription, and repair.

DNA Topoisomerase 1

An enzyme that cleaves one strand of $DNA$ which later reseals; it is a target for cytotoxic therapy.

DNA Topoisomerase 2

An enzyme that cleaves both strands of $DNA$ before it reseals; targeted by drugs like Podophyllotoxins and Anthracyclines.

Intercalation

A mechanism of action where drugs with a planar ring structure, such as Anthracyclines, insert between $DNA$ strands, causing distortion of the double helix and preventing polymerase progression.

Camptothecins

A class of Topoisomerase 1 inhibitors that act in the $S$ phase; examples include Camptothecin, Topotecan, and Irinotecan.

Podophyllotoxins

A class of Topoisomerase 2 inhibitors that act in the $S$ phase; an example is Etoposide.

Anthracyclines

A class of Topoisomerase 2 inhibitors that act in the $S$ and $M$ phases via multiple mechanisms including intercalation; an example is Doxorubicin.

Irinotecan

A prodrug topoisomerase inhibitor converted by carboxyl esterase into its active metabolite, $SN-38$.

SN-38

The active metabolite of Irinotecan that undergoes glucuronidation by $UGT1A1$ for elimination.

UGT1A1

A phase 2 enzyme responsible for metabolizing and inactivating the active form of Irinotecan ($SN-38$).

UGT1A1*28

An allele with a different number of $TA$ repeats in the promotor region leading to lower gene expression, making individuals more prone to adverse drug reactions like neutropenia.

Alkylating Agents

Cytotoxic drugs that form covalent bonds with $DNA$ through reactive species, causing cross-linking between two strands or intramolecular cross-linking.

Platinum Compounds

A class of alkylating agents, such as Cisplatin and Carboplatin, where reactive species attach to nucleotide bases to prevent $DNA$ unwinding.

Nitrogen Mustards

Alkylating agents such as Cyclophosphamide and Ifosfamide that require $CYP2B6$ activity for metabolism to become active.

Phosphoramide Mustard

The minor product of nitrogen mustard metabolism that intercalates $DNA$.

Acrolein

An extremely toxic minor product of nitrogen mustard metabolism that is administered with the adjuvant therapy Mesna for inactivation.

Mesna

An adjuvant therapy given with nitrogen mustards to lead to the formation of an inactive form of Acrolein.

Antimetabolites

Drugs with a similar structure to nucleotides that interfere with production or are incorporated into $DNA$, creating a steric block on replication.

Folate antagonists

A type of antimetabolite, such as Methotrexate, that interferes with nucleotide production.

Purine analogues

Base analogues like Azathioprine, 6-Meracaptopurine, and Thioguanine that form nucleoside mimics when linked to ribose sugar.

Uracil mimics

Pyrimidine-based antimetabolites including 5-Fluorouracil and its prodrug Capecitabine.

Gemcitabine

A cytosine mimic that inhibits $DNA$ polymerase and ribonucleotide reductase after being phosphorylated to Gemcitabine triphosphate.

Cytarabine (Ara C)

A cytosine mimic that is phosphorylated to $AraCTP$ and acts primarily by being incorporated into $DNA$.

Bleomycin

A glycopeptide antibiotic produced by Streptomyces Verticillus that binds iron and oxygen to produce reactive peroxide, causing $DNA$ strand breaks.

Microtubule Inhibitors

Drugs that stop the formation of the mitotic spindle, preventing $DNA$ separation and cell division.

Vinca alkaloids

Microtubule inhibitors such as Vinblastine and Vincristine that bind to b-tubulin to inhibit microtubule polymerisation.

Taxanes

Microtubule inhibitors such as Paclitaxel and Docetaxel that bind to b-tubulin to stabilise microtubules, preventing both polymerisation and depolymerisation.