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Pharmacology > ANTICANCER DRUGS > Flashcards

ANTICANCER DRUGS Flashcards

1
Q

Indications for Chemotherapy:
Chemotherapy is presently used in four main
clinical settings:

A
  1. Primary (induction) chemotherapy .
  2. Neoadjuvant chemotherapy .
  3. Adjuvant chemotherapy .
  4. Site-directed chemotherapy.
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2
Q

Primary Chemotherapy

A 
• Chemotherapy administered as the primary treatment in patients who present with advanced cancer for which no alternative treatment exists.
• The goals of therapy are to:
 1. Relieve tumor related symptoms.
 2.Improve overall quality of life.
 3.Prolong time to tumor progression.
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3
Q

Neoadjuvant Chemotherapy

A

• Chemotherapy is administered before surgery.
• The goal is to reduce the size of the primary
tumor so that surgical resection can then be
made easier.

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4
Q

Adjuvant Chemotherapy

A

• Administration of chemotherapy after local
treatment modalities (e.g. surgery) has been
performed.
• Destroys microscopic cells that may be present
after local treatment modalities has been done.
• Reduces the incidence of both local and systemic
recurrence and to improve the overall survival of
patients.

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5
Q

Site-Directed Chemo.

2 types?

A
  1. Direct instillation into sanctuary sites (intrathecal or peritoneal)
  2. Regional perfusion of the tumor (e.g Intra-arterial)
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6
Q

Growth Fraction
what is it?
what type of tumor cells are more responsive to chemo?

A

• Growth fraction is the percentage of actively
dividing cells at any given point in time.
• Malignant neoplasms with high growth fraction
(E.g. leukemia and lymphoma) are more sensitive to chemotherapeutic drugs.
• Low growth fraction tumors (Solid tumor e.g. carcinomas of the colon, lung cancer) are less
responsive to chemotherapeutic drugs.

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7
Q

What is the standard approach in the management of many tumor cells?

A

COMBINATION CHEMO -
1. Provides maximal cell kill within the range of
toxicity tolerated by the host for each drug.
2. Drug combinations are effective against a broader
range of cell lines.
3. Some combinations of anticancer drugs appear to
exert synergistic effect.
4. May prevent or slow the subsequent development of
cellular drug resistance.

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8
Q

Log Kill Hypothesis?

A
  • the action of a cytotoxic drug follows first order kinetics!
  • A given dose of chemo kills a constant fraction of a tumor cell population (rather than a constant number of cells)
    • Repeated doses of chemotherapy -with
    appropriate frequency- are required to eradicate
    the tumor cells.
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9
Q

Common AE due to chemo. and tx?

A

most chemotherapeutic agents have toxic effects on normal cells, particularly those with rapid rate of turnover, such as bone marrow and mucous
membrane cells.

• Nausea and vomiting
(treated with 5HT3
blockers and NK1
inhibitors).
• Stomatitis
• Alopecia
• Myelosuppression
(Filgrastim is used
to treat neutropenia).
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10
Q

Strong myelosuppressors

A 
"My strong Vin CADD"
Cytarabine
Alkylating agents 
Doxorubicin
Daunorubicin
Vinblastine
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11
Q

Moderate myelosuppression

A

Carboplatin
Methotrexate
5-FU

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12
Q

Mild Myeosuppression

A

“BAV”
Bleomycin
Vincristine
Asparaginase

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13
Q

Specific AE:
Doxorubicin

Cyclophosphamide and ifosphamide

Bleomycin

A

• Doxorubicin causes cardiotoxicity.
• Cyclophosphamide and ifosphamide cause
hemorrhagic cystitis (Mesna)
• Bleomycin causes pulmonary fibrosis.

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14
Q

Treatment-induced neoplasms are especially a problem after therapy with

A

alkylating agents.

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15
Q 
Toxicity: minimizing  AE:
Leucovorin
Mesna
Dexrazoxane
Filgrastim
Amifostine
A

• Leucovorin rescues bone marrow from methotrexate.
• Mesna reduces hemorrhagic cystitis caused by cyclophosphamide and ifosfamide.
• Dexrazoxane reduces anthracycline (doxorubicin and daunorubicin)-induced
cardiotoxicity.
• Filgrastim reverses neutropenia caused by many
anticancer agents.
• Amifostine is a cytoprotective agent that reduces renal toxicity caused by cisplatin.

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16
Q

Most important efflux pump for multdrug resistance?

A

P-Glycoprotein (permeability glycoprotein) AKA MDR1

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17
Q

what cells are more sensitive?

A

cell cycling within the cell cycle..Not cell in Go phase.

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18
Q

Cell cycle specific vs Cell cycle non specific

A

• cell cycle-specific drugs are most effective in hematologic malignancies and other tumors in which a large proportion of the cells are proliferating or are in the growth fraction.
• Cell cycle-nonspecific drugs are useful in lowgrowth
fraction solid tumors as well as in highgrowth-fraction
tumors.

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19
Q

Cell Cycle specific agents?

A 
"Bleo CAME around"
Antimetabolites
Microtubule inhibitors
Epipodophyllotoxins
Camptothecins (TOPOTECAN, IRINOTECAN) 
Bleomycin
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20
Q

Cell cycle Nonspecific agents

A

“APA”
Alkylating agents
Platinum coordination complexes
Antitumor antibiotics

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21
Q

Antimetabolites

A
  • Block S phase
    Folate analogs
    Purine analogs
    Pyrimidine analogs
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22
Q

Methotrexate (MTX) MOA

A
  • converted intracellularly to methotrexate polyglutamates which bind and inihibit DIHYDROFOLATE REDUCTASE.
  • This results in inhibition of the synthesis of THF which is involved in denovo synthesis of:
  1. deoxythymidylate nucleotides → Inhibition DNA
    synthesis.
  2. Purine nucleotides → Inhibition DNA and RNA
    synthesis
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23
Q

Leucovorin

MOA

A

• Leucovorin is N5-formyl-THF.
• Antidote to drugs that decrease levels of folic
acid, such as methotrexate, to rescue the bone
marrow.
• Leucovorin provides the normal tissues with the
reduced folate, thus circumventing the inhibition
of DHFR

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24
Q

Methotrexate Clinical applications?

A

• Breast cancer, head and neck cancer, osteogenic sarcoma, bladder cancer, choriocarcinoma,
primary central nervous system lymphoma and
non-Hodgkin’s lymphoma.

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25
Q

Methotrexate AE?

A
  • Common: Stomatitis, mucositis, myelosuppression, alopecia, nausea, vomiting.
  • Renal Damage: Uncommon. Complication of high-dose methotrexate.
  • Hepatic fibrosis and cirrhosis.
  • Pneumonitis.
  • Neurologic Toxicities. With IT administration.
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26
Q

Purine analogs

A

6-Mercaptopurine
6-Thioguanine
- similar to hypoxanthine

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27
Q

6-Mercaptopurine MOA

A
  • Converted to thio-IMP by the salvage pathway enzyme, HGPRT.
  • Thio-IMP inhibits the first step of the denovo purine ring biosynthesis.
  • Thio-IMP also blocks formation of AMP and GMP from IMP.
  • Also, dysfunctional RNA and DNA result from incorporation of guanylate analogs.
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28
Q

6-Mercaptopurine CA/AE

A

Clinical applications:
• Childhood acute leukemia (ALL).

Adverse effects:
• Nausea, vomiting and diarrhea.
• Hepatotoxicity.
• Bone marrow suppression.

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29
Q

6 Thioguanine MOA

A

6-Thioguanine is converted to the nucleotide thioguanosine monophosphate (TGMP) by
HGPRT.TGMP then:
1. Inhibits the synthesis of the Purine nucleotides (by inhibiting PRPP amidotransferase).
2. Inhibit the phosphorylation of GMP to GDP by Guanylate kinase enzyme.
3. Can be converted to TGTP and dTGTP which incorporate into RNA and DNA respectively.

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30
Q

6 Thioguanine CA/AE

A

Nonlymphocytic leukemias

Adverse effects:
• Nausea, vomiting and diarrhoea.
• Hepatotoxicity.
• Bone marrow suppression

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31
Q

6-Thioguanine CA/AE

A
  • Clinical applications:
    • Nonlymphocytic leukemias.

AE:
N/V/D
Hepatotoxicity
Bone marrow supppression

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32
Q

Pyrimidine analogs

A 
5-fluorouracil
Capecitabine
Deoxcytidine analogs
- Cytarabine
- Gemcitabine
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33
Q

5-Fluorouracil (5-FU) MOA

A

• Converted to the deoxyribonucleotide 5-FdUMP.
• 5-FdUMP inhibits thymidylate synthase. DNA synthesis is inhibited.
• ‘Thymineless death’ results.
• 5-FU is also converted to 5-FUTP and incorporated
into RNA, interfering with RNA processing and function.

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34
Q

5-Fluorouracil (5-FU)
Catalyzed by?
def of enzymes causes what toxic AE?

A 
Dihydropyrimidine dehydrogenase (DPD)
- def. of enzyme causes toxicity
  • myelosuppression, neurotoxicity and life threateing diarrhea
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35
Q

5-Fluorouracil (5-FU) CA?

A

5-FU + Leucovorin combo used for colorectal cancer

  • activity against a wide variety of solid tumors, including cancers of the breast,
    stomach, pancreas, esophagus, liver, head and
    neck, and anus.

• Can be used topically for keratoses and
superficial basal-cell carcinoma.

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36
Q

5-Fluorouracil (5-FU) AE?

A

N/V/alopecia, bone marrow depression!

  • HAND FOOT SYNDROME
  • seen after extended infusions!
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37
Q

Capecitiabine PK?

  • Its a produrg of?
  • how is it activated?
  • MOA?
A

• Orally prodrug of 5-FU
• Activated by a three-steps enzymatic conversion to
5-FU.
• The first two steps occur in the liver .
• The last step occurs in the tumor and is catalyzed
by the enzyme Thymidine phosphorylase.
• The expression of thymidine phosphorylase is higher
in many solid tumors than in corresponding normal
tissue, particularly in breast cancer and colorectal
cancer.

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38
Q

Capecitabine - CA

1st line tx. for?

A

1st line for metastatic colorectal cancer.

Metastatic breast cancer

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39
Q

Capecitabine AE?

A

Diarrhea
Hand-Foot syndrome
Myelosuppression, N/V adn mucositis. incidence less than that observed w/ intravenous 5-FU.

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40
Q

Deoxycytidine analogs

A

Cytarabine (ARA-C)

Gemcitabine (dFdC)

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41
Q

Cytarabine (ARA-C)- MOA

A

Converted to Cytarabine triphosphate which then:
1. Competitively inhibits DNA polymerase-α (blockade of
DNA synthesis).
2. Competitively inhibits DNA polymerase-β (blockade of DNA repair).
3. Incorporated into RNA and DNA. Incorporation into DNA
leads to interference with chain elongation and defective
ligation of fragments of newly synthesized DNA.

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42
Q

CYTARABINE-CLINICAL APPLICATIONS:

Is it active against active tumors?

A

• Its activity is limited exclusively to hematologic
malignancies, including acute myelogenous leukemia
and non-Hodgkin’s lymphoma.
• Not active against solid tumors.

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43
Q

CYTARABINE-AE

A
  • Myelosuppression
  • Mucositis
  • Nausea
  • Vomiting
  • Neurotoxicity (when high-dose therapy is administered).
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44
Q

GEMCITABINE MOA

A
  • Phosphorylated to nucleoside di- and triphosphate, which inhibit DNA synthesis.
  • Inhibition of ribonucleotide reductase by Gemcitabine DIphosphate, which reduces the level of deoxyribonucleoside triphosphates required for the synthesis of DNA.
  • Incorporation of Gemcitabine TRIphosphate into DNA which results in chain termination.
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45
Q

GEMCITABINE CA?

What spectrum of activity has it got?

A

•Broad-spectrum activity against:

  1. Solid tumors: including Pancreatic cancer, non small cell lung carcinoma, bladder cancer, ovarian cancer, soft tissue and sarcomas.
  2. Hematologic malignancies :( non-Hodgkin’s lymphoma).
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46
Q

GEMCITABINE AE?

A
  • Flu-like syndrome
  • Nausea and vomiting
  • Myelosuppression (neutropenia)
  • Renal microangiopathy syndromes, including hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura (rarely).
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47
Q

MICROTUBULE INHIBITORS:

A

Inhibit Metaphase of Mitosis

Vinca Alkalloids:
Vinblastine
Vincristine

Taxanes:
Paclitaxel
Docetaxel

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48
Q

VINCA ALKALOIDS- PHARMACOKINETICS

A
  • Metabolized by the liver P450 system.
  • Excreted in feces.
  • Dose modification is required in the setting of liver dysfunction.
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49
Q

VINCA ALKALOIDS-MOA

A
  • Vinca alkaloids bind to β-tubulin. This disrupts assembly of microtubules.
  • This inhibitory effect results in mitotic arrest in metaphase.
  • Adverse effects of the Vinca alkaloids such as neurotoxicity may be due to disruption of these functions.
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50
Q

VINBLASTINE CA/AE

A

Clinical applications:
•Hodgkin’s and non-Hodgkin’s lymphomas, breast cancer and germ cell cancer.

Adverse effects:
•Bone marrow suppression (the dose-limiting adverse effect).
•Alopecia.
•Peripheral neuropathy.
•Nausea and vomiting.
*Potent vesicant, and care must be taken in its administration.

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51
Q

VINCRISTINE CA?

A

Clinical applications:
1. Hematological malignancies:
•Acute lymphoblastic leukemia, Hodgkin’s and non-Hodgkin’s lymphoma.

  1. Pediatric tumors:
    •Rhabdomyosarcoma, neuroblastoma, and Wilms’ tumor.
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52
Q

VINCRISTINE AE

A

Adverse effects:
•Neurotoxicity with peripheral neuropathy.
•Paralytic ileus.
•Optic atrophy.
•Mild myelosuppression.
•Alopecia.
•Syndrome of inappropriate ADH secretion (SIADH).

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53
Q

TAXANES PK?

A

Pharmacokinetics:
•Metabolized extensively by the liver P450
- mostly excreted in feces via the hepatobiliary route.

•Dose reduction is required in patients with liver dysfunction.

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54
Q

TAXANES-MOA

A
  • Taxanes bind to the β-tubulin subunit of microtubules at a site distinct from Vinca alkaloid binding site.
  • Unlike the Vinca alkaloids, Taxanes promote microtubule polymerization and inhibit depolymerization.
  • Stabilization of the microtubules in a polymerized state arrests cells in mitosis and eventually leads to the activation of apoptosis.
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55
Q

PACLITAXEL CA?

What kind of tumors?

A

•Solid tumors including: ovarian advanced breast, lung cancer, head and neck, esophageal, prostate, and bladder cancers and AIDS-related Kaposi’s sarcoma.

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56
Q

PACLITAXEL-ADVERSE EFFECTS

Hypersensitivity is one of the adverse effects, how is it reduced?

A
  • Hypersensitivity, myelosuppression, peripheral neuropathy, alopecia, etc
  • Hypersensitivity is reduced by premedication with dexamethasone, diphenhydramine and an H2 blocker
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57
Q

What is the significance of Abraxane?

A

•Abraxane is an albumin-bound form of paclitaxel which does not cause hypersensitivity, does not require premedication, and causes less myelosuppresion than the traditional paclitaxel.

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58
Q

DOCETAXEL CA?

A
  • Second- line therapy in advanced breast cancer and non-small cell lung cancer.
  • Major activity in head and neck cancer, small cell lung cancer, gastric cancer, advanced platinum-refractory ovarian cancer, and bladder cancer
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59
Q

DOCETAXEL-ADVERSE EFFECTS:

A
  • Myelosuppression (dose-limiting).
  • Fluid retention:Pre-treatment with Dexamethasone is required to prevent fluid retention.
  • Neurotoxicity:does not cause neuropathy as frequently as Paclitaxel.
  • Mucositis.
  • Alopecia.
  • Hypersensitivity.
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60
Q

EPIPODOPHYLLOTOXINS MOA

what are the 2 drugs?

A

•Inhibit topoisomerase II, resulting in DNA damage through strand breakage.
•Block cells in the late S-G2 phase.
ETOPOSIDE
TENIPOSIDE

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61
Q

EPIPODOPHYLLOTOXINS CA/AE?

A

Etoposide for testicular and small cell cancer.

Teniposide refractory childhood acute lymphoblastic leukemia

Adverse effects:
•Nausea and vomiting.
•Alopecia.
•Myelosuppression.

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62
Q

CAMPTOTHECINS MOA

2 drugs:

A

TOPOTECAN
IRINOTECAN
•Inhibit the activity of topoisomerase I.
• Inhibition of this enzyme results in DNA damage.

63
Q

TOPOTECAN CA:

A
  • Second-line therapy for advanced ovarian cancer following initial treatment with platinum-based chemotherapy.
  • Second-line therapy of small cell lung cancer.
64
Q

TOPOTECAN PK/AE

A

•The main route of elimination is renal excretion and dosage must be adjusted in patients with renal impairment.
Adverse effects:
•Nausea and vomiting.
•Myelosuppression.

65
Q

IRINOTECAN PK:

A

“Irin likes to Poopy”
•Pharmacokinetics:
•Irinotecan is a prodrug converted in the liver to an active metabolite.
•Irinotecan and its metabolites are mainly eliminated in bile and feces, and dose reduction is required in case of liver dysfunction.

66
Q

IRINOTECAN CA/AE?

A 
Clinical applications:
•Metastatic colorectal cancer (combined with 5-FU and Leucovorin).
Adverse effects:
•Myelosuppression.
•Diarrhea.
67
Q

ANTITUMOR ANTIBIOTICS

2 drugs:

A

BLEOMYCIN (cell cycle specific) - G2 inhibition

ANTHRACYCLINES (Cell cycle nonspecific)

68
Q

BLEOMYCIN-MOA

PK

A
  • contains a DNA-binding region and an iron-binding domain at opposite ends of the molecule.

•It acts by binding to DNA, which results in single- and double-strand breaks following free radical formation.

Renal excretion

69
Q

BLEOMYCIN

CA?

A
  • Hodgkin’s and non-Hodgkin’s lymphomas.

* Germ cell tumor, head and neck cancer, squamous cell cancer of the skin, cervix and vulva.

70
Q

BLEOMYCIN AE?

A 
Adverse effects:
•The most serious adverse reaction is pulmonary toxicity (pneumonitis, fibrosis). Dose-limiting
•Skin hyperpigmentation.
•Mucositis
•*Minimal bone marrow suppression
71
Q

ANTHRACYCLINES-MOA

A
  • Binding to cellular membranes to alter fluidity and ions transport.
  • Inhibition of topoisomerase II.
  • High-affinity binding to DNA through intercalation, with consequent blockade of the synthesis of DNA and RNA, and DNA strand breakage.
  • Generation free radicals through an iron-dependent enzyme-mediated reductive process.(cause anthracycline-associated toxicity).
72
Q

ANTHRACYCLINES- ADVERSE EFFECTS

A
  1. Myelosuppression (main toxicity).
  2. Cardiotoxicity:
    •Dose-dependent, dilated cardiomyopathy associated with heart failure.
    •Due to free radicals.
  3. Erythema and desquamation of the skin observed at sites of prior radiation therapy “radiation recall reaction”.
73
Q

what can be used to reduce cardiotoxicity caused by anthracyclines?

A

•The iron-chelating agent DEXRAZOXANE can reduce the cardiotoxicity.

74
Q

ANTHRACYCLINES

A

DOXORUBICIN*** - IMPORTANT DRUG

DAUNORUBICIN

75
Q

DOXORUBICIN-CLINICAL APPLICATIONS

A
  • Major clinical activity in cancers of the breast, endometrium, ovary, testicle, thyroid, stomach, bladder, liver, and lung; in soft tissue sarcomas.
  • Used for several childhood cancers, including neuroblastoma, Ewing’s sarcoma, osteosarcoma, and rhabdomyosarcoma.
  • Active in hematologic malignancies, including acute lymphoblastic leukemia, multiple myeloma, and lymphomas.
76
Q

DAUNORUBICIN-CLINICAL APPLICATIONS

A
  • Used in the treatment of acute myeloid leukemia.

* Limited efficacy against solid tumors.

77
Q

ALKYLATING AGENTS-MOA

A

• Cell cycle-nonspecific drugs.
• Transfer of their alkyl groups to various cellular uuconstituents.
•Alkylations of DNA within the nucleus represent the major interactions that lead to cell death.
•The major site of alkylation within DNA is the N7 position of guanine.
- interactions can occur on a single strand or on both strands of DNA through cross-linking.
- Most major alkylating agents are bifunctional, with two reactive groups.

78
Q

ALKYLATING AGENTS-ADVERSE EFFECTS

A
  • Occur primarily in rapidly growing tissues such as bone marrow, gastrointestinal tract and reproductive system.
  • Nausea and vomiting (pre-treatment with 5-HT3 receptor antagonists)
  • potent vesicants and can damage tissues at the site of administration as well as produce systemic toxicity.
  • Carcinogenic*** , increased risk of secondary malignancies, especially acute myelogenous leukemia.
79
Q

ALKYLATING AGENT TYPES

A 
"Try Nitrogen MAN's mustard"
NITROGEN MUSTARDS
NITROSOUREAS
ALKYL SULFONATES
METHYLHYDRAZINES
TRIAZINES
80
Q

NITROGEN MUSTARDS

A

CYCLOPHOSPHAMIDE
IFOSFAMIDE
MECHLORETHAMINE
MELPHALAN

81
Q

CYCLOPHOSPHAMIDE CA:

PK?

A
  • most widely used alkylating agents.
    •Can be given orally or IV.
    •Breast cancer, ovarian cancer and soft tissue sarcoma.
    •Non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.
    •Neuroblastoma, Wilms’ tumor and rhabdomyosarcoma.
82
Q

CYCLOPHOSPHAMIDE PK?
Admin?
Activation?

A
  • A Prodrug administered via IV route.

* Activated in the liver, by cytochrome p450 3A4.

83
Q

CYCLOPHOSPHAMIDE AE?

A 
Adverse effects:
•Nausea and vomiting.
•Bone marrow suppression.
•Alopecia
•Sterility
•HEMORRHAGIC CYSTITIS (prevented by adequate hydration and parenteral administration of MESNA).
84
Q

IFOSFAMIDE AE?

A
  • Has virtually the same toxicity profile as cyclophosphamide, although it causes GREATER PLATELET SUPPRESSION, and urinary NEUROTOXOICITY.
  • Nausea and vomiting.
  • Bone marrow depression.
  • Alopecia.
  • NEPHROTOXICITY.
  • Hemorrhagic cystitis (prevented by adequate hydration and parenteral administration of Mesna).
85
Q

MECHLORETHAMINE PK?

A
  • Very unstable. Solutions must be made up just prior to administration.
  • Largely replaced by cyclophosphamide, melphalan and other more stable alkylating agents.
  • Powerful vesicant (given IV only).
86
Q

MECHLORETHAMINE - ADVERSE EFFECTS

A
  • Severe nausea and vomiting.
  • Severe bone marrow depression.
  • Alopecia.
  • Immunosuppression
87
Q

MELPHALAN Clinical applications:

A
  • Multiple myeloma***.
  • Breast cancer.
  • Ovarian cancer.
88
Q

MELPHALAN AE?

A
  • Bone marrow suppression.
  • Nausea, vomiting and diarrhea.
  • Oral ulceration.
  • Hepatotoxicity.
  • Pulmonary fibrosis.
89
Q

NITROSOUREAS

drugs?

A

CARMUSTINE (IV)

LOMUSTINE (Oral)

90
Q

NITROSOUREAS CA?

A
  • The nitrosoureas are highly lipid-soluble and are able to readily cross the blood-brain barrier.
  • Brain tumors.
  • Lymphomas.
91
Q

NITROSOUREAS AE/Resistance?

A
  • Myelosuppression.
  • Renal failure.
  • Pulmonary fibrosis.

Resistance:
•Non-cross-resistant with other alkylating agents.

92
Q

AKYL SULFONATES

DRUGS?

93
Q

BUSULFAN CA/AE?

A

Clinical applications:
•Chronic myelogenous leukemia.

Adverse effects:
•Myelosuppression is the main toxicity.
•Pulmonary fibrosis.

94
Q

METHYLHYDRAZINES
drug?
CA?

A

PROCARBAZINE

  • Hodgkin’s and non-Hodgkin’s lymphoma.
  • Brain tumors
95
Q

PROCARBAZINE AE?

A
  • CNS depression (acute toxicity).
  • Leukopenia and thrombocytopenia.
  • Potent immunosuppressive agent.
  • Disulfiram-like reactions.
  • One metabolite is a weak monoamine oxidase (MAO) inhibitor, and adverse events can occur when procarbazine is given with other MAO inhibitors as well as tyramine-containing foods.
  • Carcinogenic potential is higher than that of most other alkylating agents (increased risk of secondary cancers in the form of acute leukemia).
96
Q

TRIAZINES drug?

CA?

A

DACARBAZINE (DTIC)

  • Clinical applications:
  • Malignant melanoma, Hodgkin’s lymphoma, soft tissue sarcomas, and neuroblastoma.
  • Potent vesicant and care must be taken to avoid extravasation during drug administration.
97
Q

DACARBAZINE (DTIC) AE?

A

Adverse effects:
•Nausea and vomiting.
•Myelosuppression (usually mild to moderate).

98
Q

PLATINUM COORDINATION COMPLEXES:
Pharmacokinetics:
MOA?

A

•Extensively cleared by the kidneys and excreted in the urine. As a result, dose modification is required in patients with renal dysfunction

Mechanism of action:
•Binds DNA through the formation of intrastrand and interstrand cross-links, thereby leading to inhibition of DNA synthesis and function.
•The primary binding site is the N7 position of guanine.

99
Q

PLATINUM ANALOGS

A

CISPLATIN***
CARBOPLATIN

PLATIN=PLATINUM*

100
Q

CISPLATIN CA?

A

Clinical applications:
•Major antitumor activity in a broad range of solid tumors particularly testicular, ovarian, and bladder cancer.
•Its use with Vinblastine and bleomycin has been major advance in development of curative therapy for testicular cancers.

101
Q

CISPLASTIN AE?

A
  • Nausea and vomiting.
  • Mild to moderate myelosuppression.
  • Peripheral sensory neuropathy.
  • OTOTOXICITY
  • NEPHROTOXICITY.
  • Electrolyte disturbances:
  • ↓ Mg+2, ↓ Ca+2, ↓ K+1and ↓ PO4-3.
  • Anaphylactic-like reactions.
102
Q

Management of Cisplatin induced nephrotoxicity

A
  • pre-treatment hydration and diuresis.
  • Amifostine is a thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin.
103
Q

CARBOPLATIN CA/AE?

A

•Ovarian cancer, non-small cell and small cell lung cancer, breast cancer, head and neck cancer and bladder cancer.

Adverse effects:
•Less nausea, neurotoxicity, ototoxicity and nephrotoxicity than cisplatin.
•Dose-limiting toxicity is myelosuppression.

104
Q

HORMONAL AGENTS

A

GLUCOCORTICOIDS
ESTROGEN INHIBITORS
ANDROGEN INHIBITORS

105
Q

PREDNISONE:
MOA?
CA?

A

GLUCOCORTICOID:
•Induces lymphocyte apoptosis.
•Used against lymphocytes-drived neoplasm such as; acute lymphoblastic leukemia, lymphoma and multiple myeloma.
•Effective in the management of autoimmune hemolytic anemia and thrombocytopenia associated with chronic lymphocytic leukemia.

106
Q

ESTROGEN INHIBITORS

A

SELECTIVE ESTROGEN-RECEPTOR MODULATORS (SERMS)

SELECTIVE ESTROGEN-RECEPTOR DOWNREGULATORS (SERDS)

AROMATASE INHIBITORS

107
Q

SELECTIVE ESTROGEN-RECEPTOR MODULATORS (SERMS)

Drugs

A

•Bind to and activate or block estrogen receptors depending on the target tissue.

Tamoxifen
Raloxifene

108
Q

TAMOXIFEN MOA?

what kind of cancer is it used for?

A
  • SERMs bind to estrogen receptors and act as agonists or antagonist depending on the tissue.
  • Tamoxifen is an antagonist on breast cancer.
  • Tamoxifen is an agonist in nonbreast tissues.
  • Used for receptor-positive breast cancer.
  • Chemopreventive agent in women at risk for breast cancer.
109
Q

RALOXIFENE**
MOA?
why is it special?

A
  • Raloxifene is an antiestrogen in the uterus and the breast, while promoting estrogenic effects in the bone to inhibit resorption.
  • Used for prevention of postmenopausal osteoporosis and prophylaxis of breast cancer in high risk postmenopausal women.
110
Q

SELECTIVE ESTROGEN-RECEPTOR DOWNREGULATORS (SERDS)

A

FULVESTRANT

111
Q

FULVESTRANT

A
  • Pure estrogen receptor antagonist with no agonist activity.
  • Increases ER degradation.
  • Reduces the number of ER molecules in cells.
  • Used in Tamoxifen-resistant breast cancer.
112
Q

AROMATASE INHIBITORS MOA

CA

A
  • Inhibit aromatase enzyme which is required for estrone, the primary estrogen in postmenopausal women, synthesis from androstenedione.
  • Used as Adjuvant chemotherapy in estrogen receptor positive breast cancer.
113
Q

ANASTROZOLE
LETROZOLE
MOA?

A
  • Non-steroidal

- Competitive (reversible) inhibitors of aromatase enzyme

114
Q

EXEMESTANE MOA?

A

Steroidal

Irreversible inhibitor of aromatase enzyme.

115
Q

ANDROGEN INHIBITORS

A

ANDROGEN RECEPTOR BLOCKERS

GONADOTROPIN-RELEASING HORMONE ANALOGS

116
Q

ANDROGEN RECEPTOR BLOCKERS

117
Q

FLUTAMIDE

A
  • Non-steroidal, competitive antagonist at the androgen receptor.
  • Used in the treatment of prostatic carcinoma.
  • Frequently causes mild gynecomastia.
  • Occasionally cause reversible hepatic toxicity.
118
Q

GONADOTROPIN-RELEASING HORMONE ANALOGS

MOA?

A

GOSERELIN
LEUPROLIDE

•Pulsatile administration stimulates FSH and LH release from anterior pituitary. These gonadotropins stimulate the release of gonadal hormones.

119
Q

GONADOTROPIN-RELEASING HORMONE ANALOGS (GOSERELIN
LEUPROLIDE) PRODUCE WHAT KINDS OF RESPONSE?

WHAT CANCER ARE THEY USED IN?

A
  1. produces a biphasic response:
    Initial phase (flare).
    Delayed phase.
  2. Used in prostate cancer.
120
Q

SIGNAL TRANSDUCTION INHIBITORS

A

Inhibitors of EGFR (ErbB1) and HER2/neu (ErbB2)

Inhibitors of BCR-ABL & C-KIT

Inhibitors OF RAS/MAP KINASE pathways
PROTEASOME inhibitors

ANGIOGENESIS inhibitors

121
Q

Inhibitors of the EGFR tyrosine kinase

DRUGS and there CA?

A

GEFITNIB
•Non-small cell lung cancer.

ERLOTINIB
•Non-small cell lung cancer.
•Carcinoma of pancreas.

CETUXIMAB
•Colorectal cancer (efficacy of cetuximab is restricted to tumors expressing wild-type KRAS).
•Head and neck cancer

122
Q

LAPATINIB
MOA?
CA?

A
  • Inhibitor of EGFR and ErbB2.
  • Non-small cell lung cancer.
  • Carcinoma of pancreas
123
Q

TRASTUZUMAB

CA/AE?

A
  • Humanized Monoclonal antibody against ErbB2 (HER2).
  • Breast cancer with HER2 overexpression.

AE:
•Cardiotoxicity***

124
Q

IMATINIB
CA?
MOA?

A

•Inhibits the of Bcr-Abl tyrosine kinase .
CML
•Inhibits c-kit (receptor tyrosine kinase).
Kit-positive Gastrointestinal stromal tumor.
•Idiopathic hypereosinophilic syndrome

125
Q

SORAFENIB
MOA?
CA?

A
  • Inhibits the RAF serine/threonine kinase.
  • Inhibits VEGF-R2 and VEGF-R3, PDGFR-β.
  • Renal cell carcinoma.
126
Q

BORTEZOMIB
MOA
CA

A
  • Proteasome Inhibitor.
  • Induces growth inhibition and apoptosis of tumor cells.’

Clinical applications:
•Multiple myeloma.
•Mantle cell lymphoma.

127
Q

SUNITINIB
MOA?
CA?

A
  • INHIBITS Angiogenesis.
  • Inhibits VEGFR-1, VEGFR-2, and PDGFR.
  • Clinical Applications:
  • Renal cell carcinoma.
  • Gastrointestinal stromal tumor.
128
Q

MISCELLANEOUS AGENTS

A

ASPARAGINASE
HYDROXUREA
INTERFERON alpa

129
Q

ASPARAGINASE
MOA
CA

A
  • Tumor cells in acute lymphoblastic leukemia lack asparagine synthetase, they require an exogenous source of L-asparagine.
  • Depletion of L-asparagine results in effective inhibition of protein synthesis.
  • Normal cells can synthesize L-asparagine and thus are less susceptible to the cytotoxic action of asparaginase.
130
Q

ASPARAGINASE:
CA
AE

A 
Clinical application:
•Childhood acute lymphoblastic leukemia (ALL).
Adverse effects:
•Hypersensitivity.
•Decrease in clotting factors.
•Liver abnormalities.
•Pancreatitis.
•Seizures and coma.
131
Q

HYDROXYUREA-MOA

A
  • Kills cells in S phase.
  • Inhibits ribonucleotide reductase which converts ribonucleoside diphosphate to deoxyribonucleoside diphosphate.
  • This leads to depletion of deoxyribonucleoside triphosphate pool. DNA synthesis is thereby inhibited
132
Q

HYDROXYUREA CA?

A

Clinical applications:
•Malignant melanoma.
•Chronic myelocytic leukemia.
•Ovarian cancer.
•Primary squamous cell carcinomas of the head and neck, excluding the lip.
•Hydroxyurea is also used in the treatment of adult sickle cell disease (increases the level of hemoglobin F).

133
Q

HYDROXYUREA AE?

A 
Adverse effects:
•Myelosuppression.
•Nausea, vomiting and diarrhoea.
•Skin rash and hyperpigmentation.
•Macrocytosis.
134
Q

INTERFERON alpha - MOA

A
  • Stimulates natural killer cells to kill the transformed cells.
  • Increases the expression of HLA molecules on tumor cells.
135
Q

INTERFERON alpha
CA
AE

A 
Clinical applications:
•Kaposi sarcoma
•Hairy cell leukemia
•Renal cell carcinoma
•Antiviral activity against HPV(condyloma acuminata),HBV and HCV.

Adverse effects:
•Flu like symptoms.

136
Q

2 drugs for chronic myelogenous leukemia

A

Bulsulfan

Hydroxyurea

137
Q

Cardiotoxicity causing drugs

A

Doxorubicin

Trastuzumab

138
Q

AE Pulmonary fibrosis

“BlackBold MeN smoke”

A

Bulsulfan
Bleomycin
Melphalan
Nitrosoureas

139
Q

optic atrophy AE

1 drug

A

vincristine

140
Q

Treat Kaposi sarcoma

A

Paclitaxel

IFNa

141
Q

What anticancer drugs should you be careful with when administering MAO inhibitors and tyramine foods?
- also it has high carcinogenic potential, higher than most of its kind!

A

Procarbazine

- also has disulfiram like reactions

142
Q

NEPHROTOXICITY AE

A

Cisplatin (+ototxicity)
Carboplatin (+otoxicity)
Ifosfamide

143
Q

2nd line for ovarian and small cell lung cancer?

144
Q

AE peripheral neuropathy

A 
VINCRISTINE
VINBLASTINE
PACLITAXEL
DOCETAXEL
CISPLASTIN
145
Q

Drugs that inhibit RNR

A

Gemcitabine

Hydroxyurea

146
Q

Renal cell Ca. tx.

A

SORAFENIB
SUNITINIB
INFa

147
Q

NON-SMALL CELL LUNG CANCER

A 
ERLOTINIB
GEFITNIB
LAPATINIB
DOCETAXEL
GEMCITABINE
CARBOPLATIN
148
Q

EXCRETED IN FECES

A

“VIT”
IRINOTECAN (CAMPTOTHECAN)
TAXANES
VINCA ALKALOIDS

149
Q

Hodgkins Lymphoma drugs

A 
Vincristine
Bleomycin
Glucocorticoids
Dacarbazine
Procarbazine
Doxorubicin and Daunorubicin
150
Q

Non-hodgkins

A

Mechlorethamine (vesicant)

Rituximab (also CLL)

151
Q

CLL drugs

A

Chorambucil

Rituximab (also NHL)

152
Q

CML drugs

A 
Hydroxyurea
Interferon
Imatinib
Bulsulfan
Cytarabine
153
Q

hair cell leukemia

A

Interferon alpha

Pharmacology (27 decks)

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