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Medchem > Medchem midterm 2 > Flashcards

Medchem midterm 2 Flashcards

1
Q

Vincristine Class

A

Antimitotic (M phase specific)- Vinca alkaloid

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2
Q

Vincristine Uses

A

Acute leukemia, hodgkin’s lymphoma, non-hodgkins lymphoma, neurosarcoma, Wilm’s tumor.

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3
Q

Vincristine Form

A

IV (NO INTRATHECAL)

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4
Q

Vincristine Mechanism

A

Binds to microtubules

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5
Q

Vincristine Toxicities

A

PERIPHERAL NEUROPATHY, constipation, paresthesis, alopecia, Vesicant.

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6
Q

Vincrictine Notes

A

Peripheral neuropathy can be severe. If patient has history of charcot marie foot syndrome, genetic testing may be appropriate. Initially Isolated from a Periwinkle plant

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7
Q

Vinblastine Uses

A

Hodgkins Lymphoma, breast cancer

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8
Q

Vinblastine Form

A

IV

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9
Q

Vinblastine Class

A

Antimitotic (M phase) - vinca alkaloids

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10
Q

Vinblastine Mechanism

A

Binds microtubules and changes amino acid metabolism

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11
Q

Vinblastine toxicity

A

MYELOSUPPRESSION (leukopenia), leukopenia can be dose limiting. Peripheral neuropathy

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12
Q

Vinblastine ADME

A

1/2 life=24 hours, shorter than vincristine. Clearance is hepatic with CYP3A4.

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13
Q

Vinblastine Notes

A

Leukocyte count guides dosing

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14
Q

Vinorelbine Class

A

Antimitotic (M phase) - vinca alkaloid

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15
Q

Vinorelbine use

A

Lung cancer

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16
Q

Vinorelbine form

A

IV

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17
Q

Vinca alkaloid Notes

A

Light sensitive, intrathecal administration can be fatal

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18
Q

Vinorelbine mechanism

A

Binds microtubules, interfere with amino acid and glutathione metabolism, calmodulin-dependent Ca transport, cellular respiration, nucleic acid and lipid biosynthesis

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19
Q

Vinorelbine ADME

A

1/2 life=30 hours, hepatic CYP3A4

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20
Q

Vinorelbine toxicity

A

Myelosuppression (granulocytopenia), peripheral neuropathy, constipation, paresthesis, alopecia

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21
Q

Paclitaxel class

A

Antimitotic (M phase)-taxane

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22
Q

Vinorelbine ADME

A

1/2 life=30 hours, hepatic CYP3A4

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23
Q

Vinorelbine toxicity

A

Myelosuppression (granulocytopenia), peripheral neuropathy, constipation, paresthesis, alopecia

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24
Q

Paclitaxel use

A

Lung, ovarian, breast, prostate

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25
Q

Paclitaxel form

A

IV

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26
Q

Paclitaxel formulation

A

Low aqueous solubility. Mixed with CREMOPHOR/ETHANOL. These components cause infusion complications, can be reduced by premedication.

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27
Q

Paclitaxel mechanism

A

Binds microtubules and over-stabilizes them

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28
Q

Paclitaxel toxicity

A

Myelosuppression, peripheral neuropathy, alopecia

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29
Q

Paclitaxel ADME

A

1/2 life=10-20 hrs depending on dose. Mainly hepatic clearance CYP2C. High binding to albumin

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30
Q

Docetaxol Class

A

Antimitotic (M phase) - Taxane

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31
Q

Docetaxol Uses

A

Lung, breast, prostate, gastric, head and neck

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32
Q

Docetaxol Formulation

A

Low aqueous solubility - formulated in Polysorbate-80/ethanol. Can add infusion complications

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33
Q

Docetaxol Mechanism

A

Binds to microtubules

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34
Q

Docetaxol Notes

A

Purely synthetic material. More potent and toxic than paclitaxel. Binds different part of microtubule so can be used after response to paclitaxel fails.

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35
Q

Docetaxol Toxicity

A

Myelosuppression, hepatotoxicity, peripheral neuropathy, hypersensitivity, alopecia

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36
Q

Docetaxol ADME

A

1/2 life=10-15hrs Clearance mainly hepatic CYP3A4

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37
Q

Cabazitaxel Class

A

Antimitotic (M phase) - taxane

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38
Q

Cabazitaxel Uses

A

Prostate with prednisone for patients already treated with docetaxel.

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39
Q

Cabazitaxel Formulation

A

Low aqueous solubility - formulated in Polysorbate-80/ethanol. Can add infusion complications

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40
Q

Cabazitaxel Mechanism

A

Binds microtubules, more potent than paclitaxel and docitaxel

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41
Q

Cabazitaxel Toxicity

A

Myelosuppression, peripheral neuropathy, hypersensitivity, alopecia

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42
Q

Cabazitaxel ADME

A

Long 1/2 life=95hrs. Clearance hepatic CYP3A4. P-gp doesn’t transport it out of the cell as much as Paclitaxel and docetaxel, making it more potent.

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43
Q

Ixabepilone Class

A

Antimitotic (M Phase) - Epothilone

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44
Q

Ixabepilone Use

A

Breast cancer where anthracyclines was not effective.

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45
Q

Ixabepilone Formulation

A

IV, formulated with Cremophor/ethanol. Premedicate

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46
Q

Ixabepilone Mechanism

A

Binds microtubules, different spot than taxanes. Shows antiangiogenic activity

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47
Q

Ixabepilone Toxicity

A

PERIPHERAL NEUROPATHY, myelosuppression, liver toxicity, infusion and allergic reaction (due to formulation)

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48
Q

Ixabepilone ADME

A

Long 1/2 life=50hrs. CYP3A4 clearance

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49
Q

Halichondrin Class

A

Antimitotic (G2/M phase) - Halichondrin

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50
Q

Halichondrin Use

A

Metastatic Breast cancer that has been treated by at least two (taxane and anthracycline) chemo regimens.

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51
Q

Halichondrin formulation

A

Mesylate salt

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52
Q

Halichondrin Mechanism

A

Inhibits growth phase of microtubules (G2/M specific)

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53
Q

Halichondrin Toxicity

A

Myelosuppression (Neutropenia), peripheral neuropathy, alopecia, nausea, constipation. QT prolongation

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54
Q

Neutrophil Nadir

A

The nadir (low point) of neutrophil counts occurs 7-14 days after dosing chemo. It can take 2-3 weeks for neutrophil counts to return to normal. Hence a q3weeks dosing schedule.

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55
Q

Irinotecan Class

A

Topo I inhibitor - Camptothecin

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56
Q

Irinotecan Use

A

Colorectal (part of FOLFIRI)

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57
Q

Irinotecan Formulation

A

IV, contains tertiary amine and is formulated as the HCL salt

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58
Q

Irinotecan Mechanism

A

Prodrug of SN-38, prodrug is soluble, SN-38 is insoluable. SN-38 lactone has closed ring and is active, SN-38 carboxylate has open ring and is inactive. The enzymes necessary to convert the prodrug are in higher concentration in tumor cells.

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59
Q

Irinotecan Toxicity

A

Myelosuppression (neutropenia), SEVERE/UNPREDICTABLE DIARRHEA and neutropenia can cause sepsis and death. Early diarrhea caused by cholinergic symptoms and can be treated with atropine. Late diarrhea cause is unknown but loperimide can help.

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60
Q

Irinotecan ADME

A

1/2 life=10hrs; 1/2 life of SN-38=10-20hrs. metabolism through hydrolysis of Irinotecan by carboxylesterases and clucuronidation of SN-38

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61
Q

Irinotecan Polymorphism

A

10-15% of Caucasians and African Americans are homozygous for a polymorphism that expresses low levels of enzyme and as a result they glucuronidate SN-38 poorly.

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62
Q

Topotecan Class

A

Topo I inhibitor

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63
Q

Topotecan Uses

A

Lung and ovarian

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64
Q

Topotecan Formulation

A

IV and PO. Contains a tertiary amine so formulated as HCl salt. Not a prodrug, but not as effective as irinotecan.

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65
Q

Topotecan Mechanism

A

Binds directly to Topo I enzyme. Drug interactions are not an issue

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66
Q

Topotecan Toxicity

A

Myelosuppression (leukopenia, neutropenia), thrombocytopenia, diarrhea (not as bad as irinotecan), N/V. Dose adjusted according to AUC. Direct correlation between AUC and leukopenia

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67
Q

Topotecan ADME

A

1/2 life=3 hrs. Renal excretion

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68
Q

Topotecan Oral Bioavailability

A

only 40%. However, if dosed with cyclosporine A, can increase AUC 2-3 fold

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69
Q

Doxorubicin Class

A

Topo II inhibitor - Anthracyclines

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70
Q

Doxorubicin Uses

A

Many uses, leukemias, soft tissue and bone sarcomas, Wilm’s tumor, neuroblastoma, breast, ovarian, bladder, thyroid, gastric cancers. Hodgkin’s lymphoma

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71
Q

Doxorubicin Form

A

IV (light sensitive)

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72
Q

Doxorubicin Mechanism

A

Intercalates into DNA and inhibits Topo II. Also generates reactive oxygen species

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73
Q

Doxorubicin Toxicity

A

Myelosuppression, CARDIOTOXICITY (believed to be caused by the reactive oxygen species formed). Maximum of 300mg/m2 over a person’s lifetime.

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74
Q

Doxorubicin ADME

A

Quick distribution, slow elimination 1/2 life=30-40 hrs. Reduction of 7 position along with hydrolytic removal of the aminoglycone are major routes of metabolism. These metabolites are active and can contribute to cardiotoxicity. Another mechanism of cardiotoxicity involves rubicinol metabolite and its perturbation of Ca2+ channels in the heart

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75
Q

Daunorubicin Class

A

Topo II inhibitor - anthracycline

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76
Q

Daunorubicin Use

A

Leukemias

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77
Q

Daunorubicin Form

A

IV

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78
Q

Daunorubicin Mechanism

A

Intercalates into DNA inhibits topo II, generate reactive oxygen species

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79
Q

Daunorubicin Toxicity

A

Less toxic than doxorubicin, however cardiotoxicity is more of a problem. Max dose of 450 mg/m2 per lifetime. Secondary AML or MDS can occur several laters. Vesicant

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80
Q

Daunorubicin ADME

A

distributes quickly and slow elimination 1/2 life=20 hrs. Rubicinol metabolite occurs faster so it is more cardiotoxic than doxo

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81
Q

Idarubicin Class

A

Topo II inhibitor - anthracycline

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82
Q

Idarubicin Uses

A

Acute myeloid leukemia, breast cancer

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83
Q

Idarubicin Form

A

IV

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84
Q

Idarubicin Mechanism

A

Intercalates into DNA and inhibits Topo II. Generates reactive oxygen species

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85
Q

Idarubicin Toxicity

A

CARDIOTOXICITY, same toxicities as daunorubicin

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86
Q

Idarubicin ADME

A

Similar to other anthracyclines

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87
Q

Idarubicin Notes

A

lack of methoxy group relative to doxo and dauno makes it even more lipophilic and able to penetrate tissue faster, making it more effective.

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88
Q

Etoposide Class

A

Topo II inhibitor - Podophyllotoxin

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89
Q

Etoposide Uses

A

First line small cell lung cancer. Sarcomas, testicular cancer, lymphomas, leukemia, brain cancer.

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90
Q

Etoposide Form

A

IV or PO

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91
Q

Etoposide Mechanism

A

Binds to topo II. Does not possess quinone moiety, therefore no reactive oxygen species and no cardiotoxicity

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92
Q

Etoposide Toxicity

A

HYPOTENSION if given IV too quickly. Drink plenty of water to avoid renal and bladder toxicity.

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93
Q

Etoposide ADME

A

1/2 life=5-10 hrs. Excreted in feces and urine. Renal clearance is correlated with creatinine clearance, useful in dose adjustment.

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94
Q

Teniposide Class

A

Topo II inhibitor - Podophyllotoxin

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95
Q

Teniposide Use

A

Childhood acute lymphoblastic leukemia.

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96
Q

Teniposide Formulation

A

IV only. Formulatred in Cremophor/ethanol.

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97
Q

Teniposide mechanism

A

binds to topo II

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98
Q

Teniposide ADME

A

1/2 life=10 hrs. Less polar than etoposide = less renal excretion

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99
Q

Dactinomycin Class

A

Macrolide antibiotic

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100
Q

Dactinomycin Uses

A

Wilm’s tumor, sarcomas

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101
Q

Dactinomycin Form

A

IV, very potent mcg/kg

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102
Q

Dactinomycin Mechanism

A

Intercalates into DNA very well, dissociates from DNA slowly. Can bind irreversibly through quinone system. Interferes with the transcription of DNA in mRNA; can also
form some reactive oxygen species (ROS) and is a substrate of P450 reductase

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103
Q

Dactinomycin Toxicities

A

Myelosuppression, hepatotoxicity, fatigue, infection*, local inflammation if extravasation
occurs, rare but veno occlusion disease can occur; also N/V can be severe and dose limiting.

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104
Q

Dactinomycin ADME

A

Long t1/2 due to minimal metabolic breakdown

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105
Q

Dactinomycin Note

A

Because dactinomycin is
also a bacterial antibiotic, it can interfere with diagnostic assays used to identify the bacteria causing
an infection

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106
Q

Mitomycin Class

A

Macrolide antibiotic

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107
Q

Mitomycin Use

A

Gastric cancer, pancreatic cancer. Administered IV. Also, intravesically for bladder cancer

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108
Q

Mitomycin Mechanism

A

Possibly like other macrolide antibiotics, intercalates into DNA, and can bind irreversibly
through quinone system. Interferes with the transcription of DNA in mRNA. Can be activated by P450
reductase and NADPH quinone oxidoreductase (NQO1) and for ROS. Also substrate of thioredoxin
reductase

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109
Q

Mitomycin Notes

A

presence of aziridine in the molecule. Thus, recent
research has shown that mitomycin need not enter the nuclease and can also inhibit cytosolic
ribosomal (rRNA). This can cause inhibition of all (genome wide) translational silencing. This could be
the most important mechanism.

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110
Q

Mitomycin Toxicities

A

Myelosuppression, renal toxicity, pulmonary toxicity, mucositis, alopecia; rare but serious
cardiotoxicity.* *Cardiotoxicity almost always in association with previous anthracycline use. Remember the
important cardiotoxicity of the anthracyclines (daunorubicin, doxorubicin, idarubicin).

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111
Q

Mitomycin ADME

A

Metabolism is hepatic and extrahepatic; renal excretion of parent and metabolites is important
and about 10% of parent drug excreted renally. Metabolism routes are easily saturated and clearance
of the agent is inversely proportional to dose

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112
Q

Bleomycin Class

A

Macrolide Antibiotic

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113
Q

Bleomycin Uses

A

Hodgkin’s lymphoma as component in ABVD (adriamycin/bleomycin/vinblastine/dacarbazine)
regimen, NHL, squamous head and neck cancer, testicular cancer.

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114
Q

Bleomycin Mechanism

A

Intercalates into DNA, then binds DNA covalently. Importantly, the agent also binds Fe
++
and chelate in vivo and leads to generation of reactive oxygen species

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115
Q

Bleomycin Toxicities

A

Neutropenia, thrombocytopenia, pulmonary toxicity.* Myelosuppression is mild. Allergic
reaction can occur (rarely) but can lead to analphylaxis.

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116
Q

Bleomycin ADME

A

Important inactivating enzyme (bleomycin hydrase); hydrolysis of terminal amide leads to the
inactive carboxylate metabolite (change in pKa of amine from 7.3 to 9.4) alters binding to DNA in a
major way; low levels of this enzyme in skin and lung tissues. Renal impairment increase 1/2 life from 2-4 hours to over 20 hrs

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117
Q

Bleomycin Notes

A

Pulmonary toxicity is perhaps the most serious complication of bleomycin

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118
Q

Thalidomide Class

A

Immunomodulator

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119
Q

Thalidomide Uses

A

Multiple myeloma

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120
Q

Thalidomide Mechanism

A

An immunomodulator and can increase in the number of circulating natural killer cells,
and increase plasma levels of interleukin-2 and interferon-gamma. Both these cytokines are associated
with cytotoxic activity. Thalidomide also possesses anti-inflammatory and antiangiogenic properties

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121
Q

Thalidomide Toxicities

A

Teratogenic, DVT, peripheral neuropathy, sedation, constipation

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122
Q

Thalidomide ADME

A

Spontaneously hydrolyses in vivo to multiple “metabolites”; also a substrate of CYP2C19 so
potential PM concern

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123
Q

Lenolinamide Class

A

Immunomodulator

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124
Q

Lenolinamide Uses

A

Multiple Myeloma

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125
Q

Lenolinamide Mechanism

A

A direct anti-tumor effect by inhibition of the
microenvironment support for tumor cells, an immunomodulatory role like thalidomide, induces tumor
cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, anti-angiogenic
and anti-osteoclastogenic effects. Nearly 10-fold more potent than thalidomide

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126
Q

Lenolinamide Toxicities

A

Myelosuppression can be severe and dose limiting. Teratogenic, DVT.

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127
Q

Lenolinamide ADME

A

Much less breakdown compared to thalidomide; about 2/3 of the drug is excreted in the urine.
Lenolinamide is not a substrate or an inducer of CYP450 enzymes

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128
Q

Initial steroids formed from cholesterol

A

Pregnenolones and progesterones

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129
Q

Progestins are converted to…

A

Androgens

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129
Q

Androgens are converted to…

A

Estrogens

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130
Q

Most potent androgens and estrogens?

A

Androgens: testosterone and dihydrotestosterone
Estrogens: Estradiol

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130
Q

Hypothalamus secretes GnRH which acts on pituitary to release…?

A

LH or FSH

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131
Q

LH and FSH stimulate cells in testes and ovaries to produce…?

A

Androgens and estrogens.

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131
Q

Degarelix Class

A

Gonadotropin antagonist

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132
Q

Degarelix Uses

A

Prostate cancer

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132
Q

Degarelix Mechanism

A

A gonadotropin receptor antagonist and blocks release of luteinizing hormone (LH)* and
follicle stimulating hormone (FSH) from the pituitary. A form of chemical castration

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133
Q

Degarelix Toxicities

A

Hot flushes, headache, nausea, weight gain.

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133
Q

Degarelix ADME

A

Because the agent is a peptide (synthetic) it is metabolized by amino acid peptidases

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134
Q

LH acts on which cells in males to produce testosterone?

A

Leydig Cells

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134
Q

Flutamide Class

A

androgen receptor antagonist

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135
Q

Flutamide Uses

A

Hormone dependent prostate cancer (early stage); some rare cases of androgen dependent
breast cancer

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135
Q

Flutamide Form

A

PO

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136
Q

Flutamide Mechanism

A

Binds directly to the androgen receptor and prevents the binding of endogenous
androgens (testosterone and dihydrotestosterone); also, when it binds to the AR it binds in an
“antagonist” way so there is reduced translocation to the nucleus

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136
Q

Flutamide Toxicities

A

Gynecomastia; liver toxicity* that can be severe – has led to death

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137
Q

Flutamide ADME

A

Good absorption and major metabolite (α-hydroxy) which is active is formed mainly by CYP1A2;
potential interaction by CYP1A2 inhibitor (ketoconazole) or inducers; because of the short t1/2 of
flutamide (~ 9 hrs) it must be dosed q.i.d. (4 x 250 mg)

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137
Q

Nilutamide Class

A

androgen receptor antagonist

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138
Q

Nilutamide Uses

A

Hormone dependent prostate cancer (early stage); some rare cases of androgen dependent
breast cancer

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138
Q

Nilutamide Form

A

PO

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139
Q

Nilutamide Mechanism

A

Binds directly to the androgen receptor and prevents the binding of endogenous
androgens (testosterone and dihydrotestosterone); also, when it binds to the AR it binds in an
“antagonist” way so there is reduced translocation to the nucleus

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139
Q

Nilutamide Toxicities

A

Interstitial pneumonitis*, some liver toxicity but less than flutamide

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140
Q

Nilutamide ADME

A

Extensively metabolized by the liver by several P450 enzymes; overall hepatic impairment can
lead to high levels and toxicity of nilutamide; t1/2 of 50-60 hrs; dosed daily (250 mg).

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141
Q

Nilutamide Notes

A

More potent than flutamide

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142
Q

Bicalutamide Class

A

androgen receceptor antagonist

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143
Q

Bicalutamide Uses

A

Hormone dependent prostate cancer (early stage); some rare cases of androgen dependent
breast cancer

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144
Q

Bicalutamide Mechanism

A

Binds directly to the androgen receptor and prevents the binding of endogenous
androgens (testosterone and dihydrotestosterone); also, when it binds to the AR it binds in an
“antagonist” way so there is reduced translocation to the nucleus. Also some data suggest
bicalutamide can cause some decrease in levels of the AR (mechanism unknown)

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145
Q

Bicalutamide Toxicities

A

Liver and lung toxicity less severe than flutamide and nilutamide.

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146
Q

MDV3100 Class

A

Antiandrogen receptor antagonist

147
Q

MDV3100 Uses

A

Metastatic, castrate resistant prostate cancer

148
Q

MDV3100 Mechanism

A

Binds directly to the androgen receptor but in an “antagonist” manner so that it does not
cause efficient translocation of the AR into the nucleus. However, the AR which does get translocated
does not interact correctly with the response elements of DNA for proper transcription of mRNA. Also
causes decrease in levels of the AR

149
Q

MDV3100 Toxicities

A

Well tolerated

150
Q

MDV3100 ADME

A

Good absorption and CYP2C8 and CYP3A4 primarily responsible for its metabolism; active
metabolite (N-desmethyl) formed by CYP2C8. Long t1/2 of about 6 days and about 8 days for the active
metabolite

151
Q

Castrate Resistant Prostate Cancer

A

used to describe patients who have low
“castrate levels” of endogenous androgens, yet their tumors continue to grow by support of the low
levels of androgens. The explanation for this phenomenon is that the tumors themselves produce the
androgens and the generation by the testes is no longer necessary.

152
Q

Ketoconazole Class

A

Androgen synthesis inhibitors

153
Q

Ketoconazole Uses

A

Exploratory agent for hormone dependent prostate cancer and castrate resistant prostate
cancer

154
Q

Ketoconazole Form

A

PO

155
Q

Ketoconazole Mechanism

A

inhibitor of cytochrome P450 C17-hydroxylase/17,20-lyase, also called
CYP17A1

156
Q

Ketoconazole Toxicities

A

Liver toxicity with chronic use

157
Q

Abiraterone acetate class

A

androgen synthesis inhibitor

158
Q

Abiraterone use

A

Metastatic, castrate resistant prostate cancer

159
Q

Abiraterone Mechanism

A

An acetate prodrug; hydrolysis to abiraterone can occur in the plasma and liver.
Abiraterone (not the prodrug form) binds to CYP17A1 and irreversible inactivates the enzyme. The
enzyme cannot be reactivated; new enzyme must be biosynthesized

160
Q

Abiraterone Toxicities

A

Hypertension

161
Q

Abiraterone ADME

A

*Although dosed PO, the bioavailability of this drug is very low (<10%) and it has a positive
“food effect”. When taken with a meal, the Cmax and AUC can increase more than 10-fold. This issue
can be serious if a patient ignores the dosing directions repetitively. Hypertension can lead to heart
failure, especially in elderly men with compromised heart function

162
Q

Abiraterone Form

A

PO daily with food

163
Q

Tamoxifen Class

A

ER antagonist

164
Q

Tamoxifen Uses

A

ER positive breast cancer (early stage)

165
Q

Tamoxifen Mechanism

A

Binds directly to the ER and prevents the binding of endogenous estrogens (mainly
estradiol); binds to the ER it binds in an “antagonist” way, so there is reduced translocation to the
nucleus. The ER-tamoxifen complex that enters the nucleus does not lead to proper transcription of
genes in DNA

166
Q

Tamoxifen Toxicities

A

Thromboembolism, steatosis type hepatitis (fatty liver); and tamoxifen is a partial estrogen
agonist in the endometrium so it can promote endometrial cancer which can appear years later. Some
QT prolongation that might occur only with CYP3A4 inhibitors

167
Q

Tamoxifen ADME

A

4-Hydroxy-Ndesmethyltamoxifen (endoxifen) is a very active metabolite generated by CYP3A4/5 and CYP2D6; therefore
it is susceptible to the CYP2D6 polymorphism and drug-drug interaction issues (e.g. with
antidepressants that are also metabolized by CYP2D6)

168
Q

Toremifene Class

A

ER antagonist

169
Q

Toremifene Use

A

ER positive in metastatic breast cancer

170
Q

Toremifene Mechanism

A

Binds directly to the estrogen receptor and prevents the binding of endogenous estrogens
(mainly estradiol); when it binds to the ER it binds in “antagonist” and “agonist” ways so its
pharmacology is complex. The ER-toremifene complex that enters the nucleus does not lead to proper
transcription of DNA

171
Q

Toremifene Toxicities

A

QT prolongation, cardiac failure, hot flashes, arthralgia, cataracts after chronic use.

172
Q

Toremifene ADME

A

t1/2 of about 5 days and partly due to enterohepatic recycling; extensively
metabolized by CYP3A4 to less active N-desmethyl metabolite; use of agents that are strong CYP3A4
inhibitors should be avoided. Not as much 4-hydroxy metabolite formed as for tamoxifen

173
Q

Fulvestrant Class

A

ER antagonist

174
Q

Fulvestrant Use

A

ER positive metastatic breast cancer; also for patients with disease progression following prior
antiestrogen therapy.

175
Q

Fulvestrant Mechanism

A

: ER antagonist as above but also causes down-regulation of the ER, along with some
destruction of the ER

176
Q

Fulvestrant Toxicities

A

Generally well tolerated but nausea and asthenia; lower rate of arthralgias than preceding
antiestrogens

177
Q

Fulvestrant ADME

A

Fulvestrant is metabolized in the liver by CYP3A4 but not extensively. No drug interactions
appear to exist with fulvestrant.

178
Q

Enzyme responsible for synthesis of estrogens from androgens

A

CYP19A1

179
Q

Exemestane Class

A

Estrogen Synthesis inhibitor

180
Q

Exemestane Use

A

ER positive breast cancer (both adjuvant setting and later stage); also most commonly used post
tamoxifen; for postmenapausal women only

181
Q

Exemestane Form

A

PO

182
Q

Exemestane Mechanism

A

Steroidal inhibitor of CYP19A1 (aromatase) and irreversibly inhibits (kills) the enzyme.
Such an inhibitor is also called a suicide inhibitor because the enzyme attempts to convert it to an
estrogen but the enzyme is killed in the process. *Exemestane mainly inhibits non-ovarian aromatase
(adrenals, adipose tissue, cancer tissues) therefore not to be used for premenapausal women

183
Q

Exemestane Toxicities

A

Hot flushes, fatigue, arthralgia, insomnia. Because the agent lowers estrogen levels
dramatically, bone density can decrease and lead to osteoporosis over extended use..

184
Q

Exemestane ADME

A

metabolized mainly by CYP3A4

185
Q

Anastrozole Class

A

Estrogen Synthesis Inhibitor

186
Q

Anastrozole Uses

A

ER positive breast cancer (both adjuvant setting and later stage); for postmenapausal women
only

187
Q

Anastrozole Form

A

PO

188
Q

Anastrozole Mechanism

A

Non-steroidal inhibitor of CYP19A1 (aromatase) and reversibly inhibits the enzyme.
Anastrozole outcompetes with endogenous androgens for the aromatase enzyme. Anastrozole
preferentially inhibits non-ovarian aromatase (adrenals, adipose tissue, cancer tissues) therefore not to
be used for premenapausal women.* More potent than exemestane.

189
Q

Anastrozole Toxicities

A

Bone density loss appears more extreme than for tamoxifen. Generally well tolerated but
hot flushes, fatigue, arthralgia, insomnia. Anastrozole lowers estrogen levels quite effectively, so bone
density can decrease and lead to osteoporosis over extended use. Estradiol inhibits osteoclasts which
resorb bone; less estradiol allows for more bone resorption by the osteoclasts

190
Q

Anastrozole ADME

A

Absorption is rapid and good; metabolism of anastrozole occurs by several P450 enzumes to Ndealkyl and hydroxyl metabolites. Glucuronidation also occurs and excretion is mainly fecal..

191
Q

Anastrozole Note

A

Because it is non-steroidal, it avoids some off target effects of exemestane

192
Q

Letrazole Class

A

Estrogen Synthesis Inhibitor

193
Q

Letrazole Uses

A

ER positive breast cancer (both adjuvant setting and later stage); also commonly used post
tamoxifen; for postmenapausal women only

194
Q

Letrazole Form

A

PO

195
Q

Letrazole Mechanism

A

Selective for aromatase and very potent. Non-steroidal inhibitor of CYP19A1 (aromatase)
and reversibly inhibits the enzyme. *Letrazole can inhibit ovarian and non-ovarian aromatase
(adrenals, adipose tissue, cancer tissues).

196
Q

Letrazole Toxicities

A

Because the agent lowers estrogen levels dramatically, bone density can decrease and lead
to osteoporosis over extended use; arthralgia, and cases of myocardial infarction, but rare (non-QT).

197
Q

Letrazole ADME

A

Absorbed well; metabolized mainly by the liver especially CYP3A4. The dose of this agent
should be reduced to 50% if severe cirrhosis or liver dysfunction is present.

198
Q

Prednisone Class

A

Glucocorticoid

199
Q

Prednisone Use

A

Many types of cancer; has some anti-cancer properties in combination with other agents agent in
some leukemias and multiple myeloma; also aids in comfort, and anti-emetic; seldom used alone.
Administered PO. Dosage levels are variable and depend on the disease being treated as well as the
condition of the patient

200
Q

Prednisone Mechanism

A

Binds to glucocorticoid receptor. Has many effects but in oncology mainly used for its antiinflammatory and immunosuppressant effects.

201
Q

Prednisone Toxicities

A

Fluid retention, congestive heart failure, hypertension

202
Q

Tyrosine Kinase Inhibitors

A

Independent of cell cycle, cytostatic, use phosphorylation

203
Q

Imatinib Class

A

TKI

204
Q

Imatinib Use

A

Mainly Ph+ chronic myelogenous leukemia (CML), Ph+ acute lymphocytic leukemia (ALL); also cKit+ cancers of gastrointestinal stromal tissue (GIST). resistance to imatinib can develop somewhat quickly

205
Q

Imatinib Mechanism

A

targets several tyrosine kinases (esp. bcr-abl, c-kit). The abl gene encodes the
actual TK activity

206
Q

Imatinib Notes

A

important mutation (T315-I) in the abl gene can exist which causes resistance to imatinib. This mutation prevents access of imatinib to the ATP binding site

207
Q

Imatinib Toxicities

A

some possible QT prolongation

208
Q

Imatinib ADME

A

main metabolite (N-desmethyl) is formed by CYP3A4

209
Q

Nilotinib Class

A

TKI

210
Q

Nilotinib Use

A

: Ph+ leukemias but after resistance to imatinib has developed

211
Q

Nilotinib Mechanism

A

targets several tyrosine kinases (esp. bcr-abl, c-kit). About 30-50 times more potent than imatinib. Not active against tumors with the T315-I mutation

212
Q

Nilotinib Toxicities

A

QT prolongation

213
Q

Nilotinib ADME

A

Not active against tumors with the T315-I mutation

214
Q

Dasatinib Class

A

TKI

215
Q

Dasatinib Use

A

Ph+ leukemias but after resistance to imatinib has developed

216
Q

Dasatinib Mechanism

A

targets several tyrosine kinases (esp. bcr-abl, c-kit). Also more potent than imatinib and nilotinib against both resistant bcr-abl TK and
non-resistant bcr-abl TK. About 300 times more potent than imatinib for bcr-abl TK. Not active against
tumors with the T315-I mutation

217
Q

Dasatinib Toxicities

A

QT prolongation

218
Q

Dasatinib ADME

A

CYP3A4 is the primary enzyme responsible
metabolism. Imatinib can also cause a small amount of
irreversible inhibition of CYP3A4

219
Q

Bosutinib Class

A

TKI

220
Q

Bosutinib Use

A

Ph+ leukemias after resistance to imatinib and dasatinib has developed. Still not effective for
tumors with the T315-1 mutation

221
Q

Bosutinib Toxicities

A

No QT prolongation

222
Q

Gefitinib Class

A

TKI

223
Q

Gefitinib Use

A

Advanced or metastatic non-small cell lung cancer after platinum and docetaxel therapy. Later survival studies did not show benefit. Also,
lack of activity in many patients (yet still toxic) led to more restricted use; now withdrawn

224
Q

Gefitinib Mechanism

A

Inhibits the intracellular TK linked to the epidermal growth factor receptor (EGFR

225
Q

Gefitinib Toxicities

A

Interstitial pneumonitis. CYP1A1 in lung can generate reactive quinone imine metabolites. *Smokers can generate much more
of the reactive metabolites

226
Q

Gefitinib ADME

A

metabolized extensively by the liver and mainly by CYP2D6 and CYP3A4

227
Q

Gefitinib Notes

A

Mutations is EGFR tend to be activating, thus greater TK activity. These mutations tend to be
more common in Asians, women, and non-smokers

228
Q

Erlotinib Class

A

TKI

229
Q

Erlotinib Uses

A

Like gefitinib for advanced or metastatic non-small cell lung cancer after platinum and docetaxel
therapy

230
Q

Erlotinib Mechanism

A

Inhibits the intracellular TK linked to the epidermal growth factor receptor (EGFR)

231
Q

Erlotinib Toxcities

A

lung toxicity* and some liver toxicity

232
Q

Erlotinib ADME

A

Erlotinib is metabolized extensively by the liver and mainly by
CYP3A4 and CYP1A1/2

233
Q

Sorafenib Class

A

TKI

234
Q

Sorafenib Uses

A

Liver cancer and renal cell carcinoma.

235
Q

Sorafenib Mechanism

A

Inhibits multiple intracellular cell surface TKs (c-KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-
3, and PDGFR-ß) and RAF TKs (CRAF, BRAF and mutant BRAF)

236
Q

Sorafenib Toxicities

A

QT prolongation

237
Q

Sorafenib ADME

A

s. Sorafenib is metabolized extensively by
CYP3A4 so drug interactions are possible. sorafenib can competitively inhibit
(moderately) CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.

238
Q

Sorafenib Notes

A

It has been proposed that the numerous but rare toxicities caused by sorafenib are due to the
multiple TKs that sorafenib inhibits

239
Q

Sunitinib Class

A

TKI

240
Q

Suntitinib Uses

A

Renal cell carcinoma

241
Q

Suntitinib Mechanism

A

multiple cell surface TKs (PDGF-R, VEGF-R, c-KIT, RET, FLT-3, CSF-1R). Some of
these TKs are known to be important in renal cell cancer signaling (e.g. VEGF-R, RET)

242
Q

Suntitinib Toxicities

A

rare but

possible severe hepatotoxicity that has caused deaths. also QT prolongation.

243
Q

Suntitinib ADME

A

The elimination t1/2 of sunitinib is about 50 hrs, while that of the
active metabolite is about 100 hrs

244
Q

Suntitinib Notes

A

in spite of targeting many TKs, sunitinib has failed in several late stage trials for
cancers such as breast, colorectal, non-small cell lung, and prostate cancer.

245
Q

Axitinib Uses

A

Renal cell carcinoma that has become resistant to other agents

246
Q

Axitinib Mechanism

A

Inhibits several VEGF TK enzymes including VEGFR-1, VEGFR-2, VEGFR-3, PDGFR. Note that
this agent is more specific than sunitinib

247
Q

Axitinib Toxicities

A

no apparent QT prolongation.

248
Q

Axitinib Class

A

TKI

249
Q

Axtomob ADE

A

The elimination t1/2 is short and ranges from 3-6 hrs

250
Q

Lapatinib Class

A

TKI

251
Q

Lapatinib Uses

A

: Advanced breast cancer in combination with capecitabine for patients with HER2+ breast cancer;
also in combination with letrazole for postmenapausal patients that have ER+ and HER2+ breast cancer

252
Q

Lapatinib Mechanism

A

: A dual inhibitor and targets EGFR-1 and HER2/neu TKs

253
Q

Lapatinib Toxicities

A

QT prolongation; rare but potentially serious

hepatotoxicity*

254
Q

Temsirolimus Class

A

mTOR

255
Q

Temsirolimus Uses

A

: Renal cell carcinoma (RCC).Formulated in ethanol/vitamin E/ polyethylene
glycol which can cause allergic reactions

256
Q

Temsirolimus Mechanism

A

Inhibitor of the kinase of mTOR. This kinase is actually a serine-threonine kinase.In RCC, the mTOR signaling was well established as an important pathway,
therefore the development of temsirolimus was rationally driven.

257
Q

Temsirolimus ADME

A

Temsirolimus is metabolized extensively by CYP3A4 and a good substrate for the efflux
transported Pgp

258
Q

Everolimus Class

A

mTOR

259
Q

Everolimus Uses

A

RCC but after failure of sorafenib or sunitinib;

260
Q

Everolimus Mechanism

A

: Inhibitor of the kinase of mTOR (mTOR1 specifically). This kinase is actually a serinethreonine kinase

261
Q

Everolimus P13K

A

tend to be serine/threonine kinases which specifically

phophorylate serine or threonine residues.

262
Q

Everolimus LY2904002

A

serine/threonine-protein kinase. There are 500+ protein kinases in humans, and so far about 125 of these are serine/threonine
kinases.

263
Q

Perifosine Class

A

mTOR; It acts as an Akt inhibitor and a PI3K inhibitor.

264
Q

CAL101 Class

A

mTOR; A P13K inhibitor

265
Q

Vorinostat Class

A

HDAC

266
Q

Vorinostat Uses

A

Cutaneous T-cell lymphoma

267
Q

Vorinostat Mechanism

A

Vorinostat inhibits the enzymatic activity of histone deacetylases (HDACs). HDAC1, HDAC2
and HDAC3 and HDAC6 are inhibited at nanomolar concentrations.

268
Q

Vorinostat Toxicities

A

rare but potentially serious pulmonary

embolism and anemia

269
Q

Vorinostat ADME

A

Major pathway of metabolism involve glucuronidation of vorinostat. CYP enzymes do not play a large role in the metabolism of vorinostat.

270
Q

Vorinostat Notes

A

The anticonvulsant valproic acid (VPA) is a weak HDAC inhibitor and is also glucuronidated.
There can be severe thrombocytopenia and/or GI bleeding if vorinostat is administered with VPA, due
to competition for glucuronidation.

271
Q

Bortezomib Class

A

Protezome inhibitors

272
Q

Bortezomib Uses

A

Multiple myeloma and mantle cell lymphoma.

273
Q

Bortezomib Mechanism

A

: Inhibit the action of proteasomes; bortezomib causes accumulation of damaged proteins
which signals for an increase in apoptosis. For unknown reasons, multiple myeloma and mantle cell
lymphoma cells are more sensitive to proteosome inhibition than normal cells.

274
Q

Bortezomib ADME

A

: Multiple CYP enzymes participate in the metabolism of bortezomib; drug interactions are not
expected except for strong inducers (e.g. rifampin, phenytoin) or strong inhibitors (e.g. ketoconazole,
ritonavir) are co-administered.

275
Q

Carfilzomib Class

A

Protezome inhibitors

276
Q

Carfilzomib Uses

A

Multiple myeloma. Formulation includes

sulfobutylether β- cyclodextrin.

277
Q

Carfilzomib Mechanism

A

Irreversibly binds to and

inhibits the chymotrypsin-like activity of the 20S proteasome.

278
Q

Carfilzomib Toxicities

A

Quite toxic; sudden cardiac arrest;

279
Q

Carfilzomib ADME

A

High renal excretion; very short t1/2 of 1 hr or shorter; rapidly and extensively metabolized into
peptide fragments and the diol of carfilzomib, CYP enzymes play only minor role in overall
metabolism; metabolites have no known biologic activity.

280
Q

Rituximab Class

A

naked antibodies

281
Q

Rituximab Uses

A

: Refractory B-cell non-Hodgkin’s lymphoma; greater than 90% of B-cell NHL have the CD20
antigen. also for CD20+ CLL. CD20 is called the B-cell antigen.

282
Q

Rituximab Mechanism

A

chimeric antibody. CD20 antigens

283
Q

Rituximab Toxicities

A

Potential severe immune/allergic reactions, severe mucotaneous reactions, tumor lysis
syndrome, progressive multifocal leukoencephalopathy (PML)* (all in black box warning).

284
Q

Rituximab Notes

A

*Immunodeficiency or immunosuppression allows JCV (John Cunningham virus) to reactivate.
In the brain it causes the usually fatal PML by destroying oligodendrocytes. JC virus is very common in
the human population (70-90% of humans have it).

285
Q

Trastuzumab Class

A

naked antibodies

286
Q

Trastuzumab Uses

A

Breast cancer but only if HER2+, in combination with chemotherapy. The over-expression of this HER2 protein occurs in nearly 30% of breast
cancer patients. gastric cancer

287
Q

Trastuzumab Toxicities

A

Immune/allergic reactions, pulmonary edema, cardiotoxicity (all in black box warning).

288
Q

Alemtuzumab Class

A

naked antibodies

289
Q

Aletuzumab Uses

A

Chronic lymphocytic leukemia (B-cell) as a single agent for previously untreated patients.

290
Q

Alemtuzumab Toxicities

A

Severe immune/allergic reactions, severe myelosuppression, serious infections* (all in black
box warning).

291
Q

Alemtuzumab Notes

A

In addition to premedicating for immune reactions, important to premedicate with antibiotics
to prevent infections* (e.g. trimethoprim/sulfamethoxazole for Pneumocystis carinii pneumonia (PCP).

292
Q

Cetuximab Class

A

naked antibodies

293
Q

Cetuximab Uses

A

r metastatic colorectal cancer (CRC) with FOLFIRI but only for KRAS mutation negative; locally or regionally advanced squamous cell cancer of the head and neck in
combination with 5-FU and platinum or with radiation.

294
Q

Cetuximab Mechanism

A

binds to EGFR-1 on cell surface. KRAS signaling
is downstream (internal in the cell) and mutations in KRAS cause activation of signaling independent of
EGFR-1 signaling which occurs at the cell surface.

295
Q

Cetuximab Toxicities

A

Severe immune/allergic reactions, cardiopulmonary arrest (black box warnings)

296
Q

Cetuximab Notes

A

Martha Stewart (insider trading)

297
Q

Bevacizumab Class

A

naked antibodies

298
Q

bevacizumab Uses

A

Colorectal cancer in combination with 5-FU based therapy (FOLFOX or FOLFIRI); non squamous
non-small cell lung cancer in combination with carboplatin and paclitaxel; glioblastoma as a single
agent

299
Q

Bevacizumab Mechanism

A

binds to vascular endothelial growth factor (VEGF), which is the
ligand that binds to the vascular endothelial growth receptor (VEGF-R2).

300
Q

Bevacizumab Toxicities

A

Bleeding, GI perforations, stroke; cardiotoxicity especially with anthracyclines (all black box).

301
Q

Panitumbumab Class

A

naked antibodies

302
Q

Panitumumab Uses

A

: Similar to cetuximab; for metastatic CRC, but as a single agent for the treatment of epidermal
growth factor receptor (EGFR-1) expressing tumors*, with disease progression on or following
fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens (i.e. FOLFOX or
FOLFIRI).

303
Q

Panitumumab Toxicities

A

: Similar to cetuximab; still high incidence of dermatologic toxicity (rash) and immune/allergic
reactions (black box warning).

304
Q

Panitumumab Notes

A

Panitumumab is not to be used for treatment of patients with KRAS mutation-positive mCRC
or for whom KRAS mCRC status is unknown. KRAS signaling is downstream (internal in the cell) and
mutations in KRAS cause activation of signaling independent of EGFR-1 signaling

305
Q

Ofatumumab Class

A

naked antibodies

306
Q

Ofatumumab Uses

A

: Chronic lymphocytic leukemia (B-cell) that is refractory to fludarabine and alemtuzumab

307
Q

Ofatumumab Mechanism

A

binds specifically to the loop regions of the CD20

308
Q

Ofatumumab Toxicities

A 
Immune/allergic reactions (no black box)*; cytopenias (esp. neutropenia), progressive 
multifocal leukoencephalopathy (PML), pneumonia, hepatitis B reactivation**
309
Q

Ofatumumab Notes

A
  • Infusion reactions less since humanized and they tend to decrease with continued dosing;
  • *infections are actually quite common and can be of bacterial, viral, or fungal origin.
310
Q

Ipilumumab Class

A

naked anitbodies

311
Q

Ipilumumab Uses

A

Metastatic melanoma, unresectable. Useful as single agent.

312
Q

Ipilumumab Mechanism

A 
binds to the cytotoxic T-lymphocyte-associated 
antigen 4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation.This enhances the immune response.
313
Q

Ipilumumab Toxicities

A

Severe and potentially fatal immune/allergic reactions due to T-cell activation (black box
warning)

314
Q

Ipilumumab Notes

A

*CTLA-4 is the T-cell “off switch”, while CD28 is the “on switch”. **Good example of high
clinical hurdle, so lower regulatory hurdle.

315
Q

Pertuzumab Class

A

naked antibodies

316
Q

Pertuzumab Uses

A

Breast cancer but only if HER2+, in combination with trastuzumab (Herceptin) and docetaxel.

317
Q

Pertuzumab Mechanism

A

t binds specifically to the cell surface receptor HER2 similar to
trastuzumab but specifically at the dimerization domain

318
Q

Pertuzumab Notes

A

Approval based on comparison trial that showed pertuzumab + trastuzumab + docetaxel was
more efficacious based on progression free survival (PFS) than placebo + trastuzumab + docetaxel.

319
Q

Ibritumomab Class

A

Antibody conjugates

320
Q

Ibritumomab Uses

A

: Relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL); previously
untreated follicular NHL. Complicated procedure for use.*

321
Q

Ibritumomab Mechanism

A

: Same antibody as in Rituxan that targets the CD20 antigen but conjugated to a
radioisotope, Yttrium 90. ) so short lived. Remember that antibodies that target proteins or
receptors on cell surfaces are internalized.

322
Q

Ibritumomab Toxicities

A

: Serious immune/allergic reactions, severe and prolonged cytopenias, and severe cutaneous
reactions (all black box).

323
Q

Ibritumomab Notes

A

The therapeutic use of Zevalin actually includes the use of Rituximab first (Day 1). Rituximab
is again on Day 7 and then followed by Zevalin 4 hrs later. **Because t1/2 of isotope is so short it is
important to calculate/confirm the radiochemical purity of the dose given.

324
Q

Tositumomab Class

A

Antibody conjugates

325
Q

Tositumomab Uses

A

: Refractory B-cell non-Hodgkin’s lymphoma after relapse following treatment with rituximab.
Note: Given in 2-step procedure involving a (1) dosimetric dose and a (2) therapeutic dose. The
dosimetric dose is given to assess biodistribution and tumor burden in the body, as well as subsequent
drop in platelet counts. Then based on information from the dosimetric dose, the therapeutic dose is
calculated and administered.

326
Q

Tositumomab Mechanism

A

Mouse antibody that targets CD20 antigen, so similar conjugate as Rituxan and Zevalin but
incorporates different radioisotope (iodine 131;

327
Q

Tositumomab Toxicities

A

: Severe immune/allergic reactions, severe cytopenias (thrombocytopenia, neutropenia),
infections, radiation exposure (all black box).

328
Q

Tositumomab Notes

A

Important limitation of use is that only one treatment can be given. This is the way the clinical
trial was done

329
Q

Brentuximab Vedotin Class

A

Antibody conjugates

330
Q

Brentuximab Vedotin Uses

A

odgkin’s lymphoma after failure of stem cell transplant (ASCT) or after failure of at least two
prior multi-agent chemotherapy regimens. systemic
anaplastic large cell lymphoma (SALCL)

331
Q

Brentuximab Vedotin Mechanism

A

A chimeric antibody-drug conjugate consisting of three components: 1) the chimeric IgG1
antibody specific for human CD30, 2) the microtubule disrupting agent MMAE*, and 3) a proteasecleavable linker that covalently attaches MMAE to the antibody

332
Q

Brentuximab Vedotin Toxicities

A

Progressive multifocal leukoencephalopathy (PML) secondary to JC infection** (black box
warning)

333
Q

Brentuximab Vedotin Notes

A

MMAE is monomethylauristatin E (antimitotic) which is extremely toxic and failed in early
clinical trials.

334
Q

Trastuzumab Emtansine Class

A

Antibody conjugates

335
Q

Trastuzumab Emtasine Uses

A

: Potentially for HER2+ breast cancer, following progression after treatment with trastuzumab +
chemotherapy.

336
Q

Trastuzumab Emtasine Mechanism

A

Combines the targeting specificity of trastuzumab with the cell killing power of emtansine
(DM1). Emtansine (DM1) is an antimitotic agent that prevents the assembly of microtubules.

337
Q

Trastuzumab Emtasine Notes

A

Positive results reported in August 2012 that T-DM1 versus capecitabine plus lapatanib in
patients previously treated with trastuzumab and a taxane chemotherapy, showed improved
progression-free survival in patients treated with T-DM1 (median 9.6 vs. 6.4 months), along with
improved overall survival (median 30.9 vs. 25.1 months).

338
Q

Denosumab Class

A

Antibody conjugates

339
Q

Denosumab Uses

A

For prevention of skeletal-related events related to bone metastases in patients with solid
tumors

340
Q

Denosumab Mechanism

A

A human IgG2 monoclonal antibody that binds to human RANK ligand (RANKL). RANKL is a
transmembrane protein involved in the formation, function, and survival of osteoclasts, the cells
responsible for bone resorption. Thus, denosumab binds RANKL* and prevents it from activating its
receptor, RANK, on the surface of osteoclasts. Increased osteoclast activity, stimulated by RANKL, is a
mediator of bone pathology in solid tumors with bone metastases.

341
Q

Denosumab Toxicities

A

hypocalcemia, osteonecrosis of the jaw

342
Q

Denosumab Notes

A

Note this agent binds to a ligand,

not a receptor.

343
Q

Granulocyte macrophage colony-stimulating factor, GM-CSF Class

A

Supportive Agents

344
Q

Granulocyte macrophage colony-stimulating factor, GM-CSF Uses

A

: For leukopenia to shorten time to white cell depletion recovery during chemotherapy, and to
reduce the incidence of severe and life-threatening infections

345
Q

Granulocyte macrophage colony-stimulating factor, GM-CSF Mechanism

A

neutrophils, macrophages and myeloid derived dendritic cells.

346
Q

Granulocyte macrophage colony-stimulating factor, GM-CSF Toxicities

A

Drugs which may potentiate the myeloproliferative effects such as lithium and
corticosteroids, should be used with caution.

347
Q

Granulocyte colony-stimulating factor, G-CSF Class

A

Supportive Agents

348
Q

Granulocyte colony-stimulating factor, G-CSF Uses

A

: For neutropenia, to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in
patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a
significant incidence of severe neutropenia with fever

349
Q

Granulocyte colony-stimulating factor, G-CSF Mechanism

A

Regulates the production of neutrophils within the bone marrow and affects neutrophil
progenitor proliferation

350
Q

Granulocyte colony-stimulating factor, G-CSF Toxicities

A

Drugs which may potentiate the myeloproliferative effects

such as lithium and corticosteroids, should be used with caution.

351
Q

Epoetin Class

A

Supportive Agents

352
Q

Epoetin Uses

A

For the treatment of anemia in patients with non-myeloid malignancies where anemia is due to
the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of
two additional months of planned chemotherapy.

353
Q

Darbopoietin Class

A

Supportive Agents

354
Q

Darbopoietin Uses

A

for the treatment of anemia in patients with non-myeloid malignancies where
anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there
is a minimum of two additional months of planned chemotherapy.

355
Q

Bisphosphonates Class

A

Supportive Agents

356
Q

Bisphosphonates Uses

A

Also for reducing skeletal events associated with cancer

such as multiple myeloma or breast cancer

357
Q

Ondansetron Class

A

Antiemetics

358
Q

Ondansetron Uses

A

Prevention of nausea and vomiting caused by emetogenic chemotherapy or radiation.
Administered PO as tablet, disintegrating tablet, or solution (2-3 times daily)

359
Q

Ondansetron Mechanism

A

A serotonin 5-HT3 receptor antagonist;

360
Q

Ondansetron Toxicities

A

Generally well tolerated,

361
Q

Ondansetron ADME

A

Elimination t1/2 about 4-6 hrs.

362
Q

Ondansetron Notes

A 
Originally approved (1991) without QT warning. QT warning added in June 2012 (no black 
box).
363
Q

Granisitron Class

A

Antiemetics

364
Q

Granisitron Uses

A

As for ondansetron; prevention of nausea and vomiting caused by emetogenic chemotherapy or
radiation. Administered PO as tablet or solution, (1-2 times daily). Also IV solution and transdermal
patch.

365
Q

Granisitron ADME

A

Elimination t1/2 about 9-12 hrs.

366
Q

Bisphosphonates Class

A

Supportive Agents

367
Q

Bisphosphonates Uses

A

Also for reducing skeletal events associated with cancer

such as multiple myeloma or breast cancer

368
Q

Ondansetron Class

A

Antiemetics

369
Q

Ondansetron Uses

A

d

370
Q

Ondansetron Mechanism

A

d

371
Q

Ondansetron Toxicities

A

d

372
Q

Ondansetron

A

d

373
Q

Ondansetron Notes

A 
Originally approved (1991) without QT warning. QT warning added in June 2012 (no black 
box).
374
Q

Granisitron Class

A

Antiemetics

375
Q

Granisitron Uses

A

As for ondansetron; prevention of nausea and vomiting caused by emetogenic chemotherapy or
radiation. Administered PO as tablet or solution, (1-2 times daily). Also IV solution and transdermal
patch.

376
Q

Granisitron ADME

A

Elimination t1/2 about 9-12 hrs.

377
Q

Palonsetron Class

A

Antimetics

378
Q

Palonsetron Uses

A

As for ondansetron and granisetron; prevention of nausea and vomiting caused by emetogenic
chemotherapy or radiation. Administered IV.

379
Q

Palonsetron Mechanism

A

As for ondansetron and granisetron; more potent than either.

380
Q

Palonsetron ADME

A

Elimination t1/2 about 40 hrs.

381
Q

gg

A

gg

Medchem (1 decks)

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