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Chemotherapy Pharmacology agents Flashcards

1
Q

What are the cell cycle nonspecific agents?

A
  1. Alkylating agents
  2. Anthracyclines
  3. Nitrosoureas
  4. Platinum agents
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2
Q

What are the cell cycle specific chemotherapy agents?

A
  1. Antimetabolites
  2. Vinas
  3. Taxanes
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3
Q

What are some of the alkylating agents? (Creates direct crosslinks of base pairs)

A
  1. Cyclophhosphamide
  2. Ifosfamide
  3. Melphalan
  4. Busulfan
  5. Mechlorethamine
  6. Chlorambucil
  7. Thiotepa
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4
Q

What are some of the typical alkylator toxicities?

A
  1. Myelosuppression
  2. N/V
  3. Secondary malignancies
  4. Interfility/impaired fertility
  5. Hemorrhagic cystitis (ifosfamide>cyclophosphamide)
    - Need to use Mesna with since acrolein metabolite is formed
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5
Q

What are some of the platinum compounds? (atypical alkylators)

A
  1. Cisplatin, carboplatin, oxaliplatin
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6
Q

What are some of the toxicities of platinum compounds (atypical alyklators)

A
  1. Peripheral neuropathies (oxaliplatin: cold sensitivity)
  2. Nephrotoxic (cisplatin)
  3. N/V
  4. Thrombocytopenia
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7
Q

What are some of the nitrosoureas? (Atypical alkylators)

A
  1. BCNu (Carmustine)

2. CCNu (Lomustine)

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8
Q

What are some of the toxicities of nitrosoureas?

A
  1. Pulmonary (BCNu)
  2. Myelosuppression
  3. N/V
  4. Phlebitis
  5. CNS (BCNU w/ etOH diliution)
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9
Q

What steps do antimetabolites inhibit?

A

Structurally similar to compounds needed for cell function. They inhibit DNA replication and repair with S phase specificity

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10
Q

What are some examples of folate antagonists (antimetabolites)?

A
  1. Methotrexate (Higher doseases require leucovorin for urine alklanization). Toxicities include mucositis and myelosuppression
  2. Pemetrexed: Need to supplement with folic acid and B12
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11
Q

What are some pyrimidine analogues (Antimetabolites)?

A
  1. Fluouracil (Can be given bolus or continuous. Continuous infusion may lead to GI symptoms. BOlus may lead to myelosuppression)
  2. Capecitabine (oral fluouracil prodrug that can cause hand-foot syndrome)
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12
Q

Leucovorin aids by what mechanism?

A

Increases 5FU binding affinity to thymidilate synthase. LCV leads to N5,N10 methylene THF

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13
Q

What are some pyrimidine antagonists (antimetabolites)?

A
  1. Cytarabine (Ara-C)
    - Needs continuous infusion and high dose
    - High dose may lead to cerebellar toxicity (increased incidence with renal dysfunction, creatinine>2)
    - Conjunctivitis (excreted from tear ducts)
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14
Q

What are some of the purine antagonists?

A
  1. 6-Mercaptopurine
  2. Gemcitabine
  3. Cladribine (2-CDA)
  4. Fludarabine
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15
Q

What are the microtubule targetting agents?

A
  1. Vinca alklaloids (Vincristine, Vinblastine, VInorelbine)

2. Taxanes (Paclitaxel, docetaxel)

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16
Q

What step do microtubule targetting agents target for vina alkaloids? And what are some toxicities?

A

M-phase cell cycle activity microtubule DESTRUCTION; cumulative neurotoxicties and variable myelosuppression (FATAL IF ADMINISTERED INTRATHECALLY)

17
Q

What step do microtubule targetting agents target for Taxanes? And what are some toxicities?

A

M-phase cell cycle activity microtubular STABILIZATION; myelosuppression, peripheral neuropathies, hypersensitivity

18
Q

Roles of topoisomerase I and II

A

I: Relaxing supercoiled DNA before transcription
II: Recoiling DNA after transcription

19
Q

Types of topoisomerase I inhibitors? Toxicities?

A

Camptothecins (Topotecan, Irinotecan); Myelosuppression, diarrhea (irinotecan) that is self limiting if early onset and life threatening if late onset

20
Q

Examples of topoisomerase II inhibitors? Toxicities?

A

Etoposide, teniposide; Myelosuppression, secondary malignancies (AML w/11q23) and mucositis

21
Q

Action of anthracyclines?

A

Intercalate DNA and inhibit topoisomerase. Secondary mechanism include free radial damage and perhaps some alkylation

22
Q

What are some toxicities of anthracyclines?

A
  1. Myelosuppression
  2. All cause Cardiac toxicity (Doxorubin (max lifetime 450, daunorubiin max lifetime 400, idarubicin max lifetime 400)
  3. Mucositis
  4. Extravasation
23
Q

Mechanism of bleomycin?

A

Low hydrolase enzyme in lung that leads to endothelial cell injury and cytokine release. Oxygen free radicals and lipid peroxiation of membrane phospholipids. Interstitual edema and stimulation of lung fibroblasts and collagen production

24
Q

Pulmonary toxicities from Bleomycin?

A
  1. Interstitial pneumonitis
  2. Pulmonary fibrosis
  3. Hypersensitivity pneumonitis
25
What are the classes of horomonal therapy for breast cancer?
1. Anti-estrogens | 2. Aromatase inhibitors
26
What are some examples of anti-estrogens and aromatase inhibitors?
Anti-estrogens: Tamoxifen, fulvestrant, Megestrol acetate (used as chemotherapy and appetite stimulant) Aromatase inhibitors: Anastrozole, letrozole, exemestane (irreversible)
27
What are some examples of hormonal therapy for prostate cancer?
1. Antiandrogens 2. LHRH agonists 3. GnRH antagonist 4. CYP17 inhibitors
28
What are some examples of monoclonal antibodies
(More toxicities less human)Murine, chimeric, humanized, Human (less toxicities more human)
29
Roles of bevacizumab?
Monoclonal antibody against VEGF-R, used for solid tumors. Toxicities include proteinuria and GI perforation
30
Roles of cetuximab?
Monoclonal antibody against EGFR, used for solid tumors. Toxicities include severe hypersensitivity rxns and acneiform rash (correlates with survival)
31
Role of imatinib meslate?
Protein tyrosine kinase inhibitor that inhibits Bcr-Abl tyrosine kinase. Inhibits proliferation and induces apoptosis in Bcr-abl positive cell lines. CML
32
Toxicities with tyrosine kinase inhibitors?
Acneiform rash (more associated with EGFR directed therapies. Treat with supportive measures and if severe may require dose reduction/delays)
33
Examples of immunotherapy therapeutic agents?
1. Ipilimumab (anti-CTLA-4) 2. Pembrolizumab-anti pd1 3. Nivolumab- Anti-pd1 4. sipulecel-t 5. High-dose II-2 6. Interferon
34
Role that CTLA-4 has and ipilimumab has as an inhibitor of CTLA-4?
CTLA-4 is normally expressed to turn off the immune system. Tumors will overexpress CTLA-4. Ipilimumab will block CTLA-4 which keeps the immune cells active. These immune cells will attack tumors then
35
AEs with ipilimumab?
1. Rash, liver toxicity, diarrhea, hypophysitis

Hematology (6 decks)

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