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NUNA 679 - ANP Pharm > Antineoplastic Drugs > Flashcards

Antineoplastic Drugs Flashcards

1
Q

What is the MOA of alkylating agents?

A

They transfer an alkyl group to the DNA of rapidly proliferating cells and disrupt the process leading to cell destruction

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2
Q

What drug classes fall under alkylating agents and related drugs? (3)

A

Nitrosoureas
Nitrogen mustards
Platinum coordination complexes

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3
Q

Discuss the pharmacokinetic factors of alkylating agents and related drugs regarding cell phase.

A

Phase-nonspecific, dose-dependent

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4
Q

What are the 4 main side effects of alkylating agents and related drugs?

A

Emetogenic
Vesicant
Mutagenic (rare)
Myelosuppressive (often dose-limiting)

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5
Q

Name 3 nitrosoureas.

A

Carmustine
Lomustine
Semustine

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6
Q

Name 2 nitrogen mustards.

A

Cyclophosphamide

Ifosfamide

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7
Q

Which alkylating drug class consists of prodrugs that require hydroxylation by CYP450? Which drug is activated more slowly?

A

Nitrogen mustards; ifosfamide is activated more slowly than cyclophosphamide

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8
Q

What is the highly toxic compound formed during the activation of nitrogen mustards?

A

Acrolein

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9
Q

What can acrolein cause?

A

Hemorragic cystitis/renal damage

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10
Q

How can you circumvent the toxic effects of acrolein?

A

Aggressive IV hydration

Using Mesna, a drug which forms a complex with acrolein and inactivates it

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11
Q

What are the major AEs of nitrogen mustard toxicity? (4)

A

Emetogenic
Myelosuppression
Alopecia
Mucosal ulcerations (dose-limiting)

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12
Q

Name 3 platinum coordination complexes.

A

Cisplatin, carboplatin, and oxaliplatin

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13
Q

What are the major toxicities of platinum coordination complexes?

A

RENAL
OTOTOXICITY
Profound nausea and vomiting/anticipatory
Electrolyte disturbances (HYPOMAGNESEMIA)

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14
Q

Describe the pharmacokinetics of platinum coordination complexes.

A 
Highly protein bound (cisplatin)
RENAL EXCRETION (AND ACCUMULATION WHICH CAN LEAD TO TOXICITY)
Large VD (Oxaliplatin - long duration of action)
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15
Q

Why is cisplatin still used if it has a higher SE profile than oxaliplatin?

A

Very effective against certain cancers

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16
Q

Name the cell cycle-specific drug classes.

A

Antimetabolites

Natural Products - Vinca Alkaloids, Taxanes, Anthracycline Antibiotics

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17
Q

Name an antimetabolite.

A

Methotrexate

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18
Q

What is the MOA of methotrexate?

A

INHIBITS DIHYDROFOLATE REDUCTASE which is required for the synthesis of normal DNA/RNA bases. MTX inhibits dTMP (thymidine monophosphate) synthesis which then inhibits DNA synthesis.

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19
Q

MTX interferes with the _______ cycle in the human body, contributing to toxicity. Therefore, __________ is given as “rescue” therapy.

A

folate; leucovorin

20
Q

What is leucovorin?

A

Fully reduced folate

21
Q

What are 2 significant mechanisms of resistance against MTX?

A

MUTATED DHFR WHICH HAS DECREASED AFFINITY FOR MTX

GENE AMPLIFICATION OF DHFR

22
Q

What AE of MTX is usually dose-limiting?

A

Mucosal ulcerations/GI toxicity

23
Q

What pharmacokinetic property of MTX can lead to a major toxicity as well as a major DDI?

A

90% renal excretion - renal toxicity and DDI with NSAIDs which decrease the excretion of MTX through decreased RBF and GFR

24
Q

Name 3 natural products (plant alkaloids) that have the same mechanism of resistance.

A 
Vinca Alkaloids (flower)
Taxanes (yew bark)
Anthracycline Abx (fungus)

Mech is P-glycoprotein inducement

25
Q

Name 4 vinca alkaloids.

A

Vincristine, vinblastine, vindesine, vinorelbine

26
Q

What is the MOA of vinca alkaloids?

A

Bind to tubulin and prevent polymerization of microtubules; CCS for M phase.

27
Q

Considering the MOA of vinca alkaloids, what is the major toxicity of concern?

A

Motor neuron and central neurotoxicity since microtubules are important for axonal integrity and transport.

28
Q

What is the major mechanism of resistance for vinca alkaloids?

A

P-glycoprotein

29
Q

What is the MOA of taxanes?

A

Alter microtubules through uncontrolled polymerization; work primarily in M-phase of cell cycle

30
Q

Due to MOA, what is the major toxicity caused by taxanes?

A

Peripheral neuropathy because of abnormal microtubules

31
Q

Name 2 taxanes.

A

Paclitaxel, docetaxel

32
Q

Why do taxanes sometimes cause a hypersensitivity reaction upon infusion?

A

Ethanol/castor oil vehicle used due to limited solubility

33
Q

How can you pretreat against a taxane infusion reaction?

A

Dexamethasone and antihistamines

34
Q

What are 2 mechanisms of resistance for taxanes?

A

P-glycoprotein

Mutated tubulin

35
Q

Name 5 anthracycline antibiotics.

A

DOXORUBICIN

Daunorubicin, valrubicin, epirubicin, idarubicin

36
Q

Name the MOAs of anthracycline antibiotics (3).

A

DNA intercalator (insert between 2 strands/prevent unwinding)
Inhibit topoisomerase II (prevents unwinding and clipping of DNA)
Generation of reactive oxygen species (leading to apoptosis of cancer cells)

37
Q

What are the mechanisms of resistance for anthracyclines? (3)

A

P-glycoprotein
Mutations in Topo II
Increased activity of glutathione peroxidase (decreases ROS)

38
Q

What is the major toxicity of concern for anthracyclines and why?

A

Cardiotoxicity; associated with doses greater than 550 mg/m2. Probably due to the generation of ROS. May cause CHF unresponsive to digoxin therapy!

39
Q

How can you prevent cardiotoxicity caused by anthracyclines?

A

Treat patient with iron-chelating agent dexrazoxane!

40
Q

What can occur up to 6 months after treatment with anthracyclines after implementing another cancer therapy?

A

Radiation recall reaction

41
Q

What is a drug with a different toxicity profile and MOA from other antineoplastic agent making it ideal for combination regimens?

A

Bleomycin

42
Q

Describe the MOA of bleomycin.

A

Molecule contains a DNA-binding region and an iron-binding domain at opposite ends. Forms a complex with iron and “shunts” electrons from iron to molecular oxygen, forming ROS that destroy the DNA.

43
Q

What enzyme prevents bleomycin toxicity in the liver, spleen, and bone marrow?

A

Bleomycin hydrolase which inactivates bleomycin (can also be a mechanism of resistance in tumor cells)

44
Q

Where is bleomycin hydrolase NOT present in the body, resulting in concerns for toxicity?

A

Skin and lungs

45
Q

What are the major toxicities of concern with bleomycin?

A

Cutaneous and pulmonary toxicity

46
Q

What an important anesthesia implication with recent bleomycin therapy?

A

Run low FiO2s to prevent ROS/pulmonary toxicity

47
Q

What is the mechanism of resistance with bleomycin?

A

Increased hydrolase activity

NUNA 679 - ANP Pharm (9 decks)

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