Pharmacology of Chemotherapy

A comprehensive set of vocabulary flashcards covering the major cytotoxic chemotherapeutic classes, mechanisms of action, specific drug characteristics, and toxicity management strategies.

Cell cycle specific (CCS)

Agents whose cytotoxic effect is exerted on the proportion of cells in a specific part of the cell cycle where the agent is active; often administered as a continuous infusion.

Cell cycle nonspecific (CCNS)

Agents whose cytotoxic effect is exerted on cells in any phase of the cell cycle, potentially preferring proliferating cells; cell kill is proportional to dosage (dose dependent).

Alkylating Agents Mechanism

Covalently binding reactive alkyl groups with nucleophilic groups of proteins and nucleic acids, causing cross-linking of DNA base pairs, most commonly at the $N7$ position of guanine.

Mesna

An agent coadministered with high-dose cyclophosphamide ($\text{~} ≥ 50 mg/kg/dose$) or ifosfamide to conjugate the toxic metabolite acrolein and prevent hemorrhagic cystitis.

Temozolomide

A lipophilic alkylating agent that methylates DNA and readily crosses the blood–brain barrier with activity in the central nervous system (CNS).

Calvert formula

The formula used to calculate carboplatin dosage: $\text{Carboplatin dose} = \text{Target AUC} \times (\text{GFR} + 25)$, where GFR is in $mL/min$.

Cisplatin

A highly emetogenic platinum agent associated with renal impairment, ototoxicity, and a requirement for pretreatment hydration and maintenance of urinary output.

Oxaliplatin

A platinum agent that causes cold-induced acute neurotoxicity (peripheral neuropathy) and oropharyngeal dysesthesia; it must be flushed with dextrose $5$ in water.

Amifostine

A chemoprotectant administered at $910 mg/m^2$ IV used to prevent cisplatin-induced nephrotoxicity and neutropenia by scavenging free radicals.

Leucovorin (with Fluorouracil)

A precursor to reduced folate that stabilizes the binding of FdUMP to thymidylate synthetase (TS), providing prolonged inhibition and improved outcomes in colorectal cancer.

Thiopurine methyltransferase (TPMT)

An enzyme involved in the metabolism of mercaptopurine and thioguanine; deficiency results in increased drug levels and high risk for severe myelosuppression.

Uridine triacetate

An antidote that may aid in recovery after fluorouracil or capecitabine overdose or severe toxicity.

Methotrexate (MTX)

An antifolate that binds dihydrofolate reductase ($DHFR$) to inhibit the formation of reduced folates; at high doses ($500–1000 mg/m^2$ or more), it requires leucovorin rescue.

Glucarpidase

An enzyme that hydrolyzes methotrexate into inactive metabolites; indicated for patients with delayed MTX clearance due to renal impairment.

Anthracyclines

A class (e.g., doxorubicin, daunorubicin) that induces apoptosis via DNA intercalation, Topoisomerase II inhibition, and the generation of semiquinone and oxygen free radicals.

Dexrazoxane

An iron chelator used as a chemoprotectant to prevent doxorubicin-induced cardiomyopathy ($10:1$ dosing ratio) and as a treatment for anthracycline extravasation.

Mitoxantrone

An anthracenedione that resembles anthracyclines and can cause blue-green discoloration of urine, tears, and saliva.

Etoposide

A Topoisomerase II inhibitor derivative of the mayapple root that causes cell cycle arrest in the late S and early $G2$ phases.

Irinotecan

A Topoisomerase I inhibitor prodrug activated to $SN\text{-}38$; characterized by acute cholinergic diarrhea (treated with atropine) and delayed diarrhea (treated with loperamide).

Taxanes

Microtubule inhibitors (e.g., paclitaxel, docetaxel) derived from yew trees that bind to and stabilize polymerized tubulin, interfering with mitosis during the M phase.

Vinca Alkaloids

Mitotic inhibitors (e.g., vincristine, vinblastine) that bind tubulin to inhibit polymerization and disrupt microtubule assembly; they must NEVER be administered intrathecally.

Proteasome Inhibitors

Agents like bortezomib and carfilzomib that inhibit the $26S$ proteasome, leading to the accumulation of $IκB$ and inhibition of the $NF\text{-}κB$ pro-proliferation pathway.

Bortezomib Neuropathy Management

Strategy to minimize neuropathy including changing the route from IV to subcutaneous and/or adjusting frequency from twice to once weekly.

Bleomycin

An antitumor antibiotic that causes DNA strand scission via free radical formation; major toxicities include pulmonary fibrosis and idiosyncratic reactions.

Arsenic Trioxide ($As_2O_3$)

A differentiating agent used in APL that induces apoptosis and causes DNA fragmentation; requires monitoring for differentiation syndrome and $QT$ prolongation.

All-trans retinoic acid (ATRA)

An oral differentiating agent for APL that binds $PML\text{-}RARα$ fusion products; known for a black box warning for differentiation syndrome.

Asparaginase

An enzyme (e.g., peg-asparaginase) that catalyzes the conversion of $L\text{-}asparagine$ to aspartic acid and ammonia, depriving certain cancer cells of a nonessential amino acid.

Histone Deacetylase (HDAC) Inhibitors

Epigenetic modifiers (e.g., vorinostat, romidepsin) that lead to the accumulation of acetylated histones, activating gene transcription for apoptosis.

P-glycoprotein (ABCB1)

An ATP-binding cassette ($ABC$) transporter that acts as an efflux pump, contributing to multidrug resistance (MDR) for taxanes, anthracyclines, and vinca alkaloids.

Radiation Recall

An acute dermatologic reaction at the local site of prior irradiation triggered by subsequent chemotherapy administration of agents like dactinomycin or doxorubicin.

Vesicants

Chemotherapy agents (including anthracyclines, vincas, and mechlorethamine) capable of causing tissue necrosis or blisters if leaked into surrounding tissue (extravasation).

Hyaluronidase

An agent used to treat extravasation of vinca alkaloids and taxanes by degrading hyaluronic acid to promote drug diffusion and absorption.