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Antineoplastics Flashcards

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1
Q

MOA of methotrexate?

A

inhibits dihydrofolate reductase

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2
Q

Indication of methotrexate?

A

ALL lymphomas

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3
Q

Indication, Solid Tumor, breast, head neck CA, Osteogenic Sarcoma Anti-inflamm effects (RA, psoriasis, autoimmune)

A

methotrexate

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4
Q

Adverse effects of methotrexate? (3)

A

DLT, GIT, severe mucositis

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5
Q

Early sign of MTX toxicity?

A

severe mucositis

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6
Q

Is MTX able to pass thru BBB?

A

yes

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7
Q

Elimination of MTX?

A

renal

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8
Q

Antidote for MTX?

A

leucovorin or folinic acid

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9
Q

Leucovorin administration after methotrexate when

A

24-36 hrs

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10
Q

MOA of leucovorin?

A

FH4 supplement

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11
Q

Half life of MTX?

A

triphasic;
Distribution phase : 30-45 mins
Clearance phase : 3-4 hours
Terminal phase: 6-20 hours

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12
Q

function of leucovorin? (2)

A

Salvage normal cells, limit toxicity to the bone marrow and GIT (Limitss MTX toxicity)

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13
Q

how many times is MTX converted by dihydrofolate reductase?

A

2

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14
Q

MOA of 5-FU?

A

Inhibits thymidilate synthetase

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15
Q

What phase of the cell cycle is 5-FU?

A

S-phase specific pyrimidine antagonist

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16
Q

function of thymidylate synthetase?

A

converts dUMP to dTMP = thymidine

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17
Q

What analog is 5-FU

A

Pyrimidine

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18
Q

Indication of 5-FU (3)

A

Colon CA, Breast CA, Head/Neck CA

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19
Q

AE of 5-FU (5)

A

Myelosuppression (4-7 days) recovery: 14 days
GI, Hepatic, Renal, CNS Toxicity

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20
Q

Route of administration of MTX? (5)

A

PO, IM, IV, SC, Intrathecal

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21
Q

Route of administration of 5-FU?

A

IV
and Oral, causes degradation of Dihydropyrmidine dehydrogenase = ineffective)

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21
Q

Oral version of 5-FU

A

Capecitabine

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22
Q

Metabolism of 5-FU

A

Liver: Dihydro fluorouracil

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23
Q

Combination of 5-FU

A

FOLFOX (Oxaliplatin)
FOLFIRI (Irinotecan)

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24
MOA of Cytobine Arabinoside (ARA-C)
Ara-CTP -> Inhibits DNA polymerase
25
What phase of the cell cycle is ARA-C?
S- Phase specific pyrimidine antagonist
26
What is ARA C DOC for?
Acute Myelogenous Leukemia (AML)
27
Indication of ARA-C (not DOC)
Meningeal Leukemia
28
Adverse effects of ARA-C in the CNS (3)
Fever, Seizures, Arachnoiditis (4-7 days)
29
AE of ARA-C (3)
DLT (transfusion needed) (10 days after treatment, reversible after 21 days) GI Toxicity Hepatotoxic CNS Toxicity (Conjuctivitis, & Arachnoiditis)
30
What specimen did ARA-C come from?
Cryptotheca crypta
31
Administration of ARA-C
ONLY IV and intrathecal
32
Elimination of ARA-C
Kidney (Ara-U)
33
MOA of Fludarabine (2)
Inhibits DNA synthesis by incorporating a false nucleotide Inhibits polymerase, ligase & primase causing chain termination
34
what phase of the cell cycle is Fludarabine?
S phase specific pyrimidine antagonist
35
Indication of Fludarabine (3)
SINGLE MOST ACTIVE AGENT IN CLL (Chronic lymphocytic leukemia) Lymphoma Macroglobulinemia
36
AE of Fludarabine (3)
DLT, GI, CNS (Progressive encephalopathy, cortical blindness, death in high dose)
37
route of administration of Fludarabine
IV Only (oral yields fluoroadenine - toxic)
38
MOA of Hydroxyurea
inhibits ribonucleotide reductase -> Inhibits DNA synthesis
39
Analog of hydroxyurea
Urea
40
Phase of cell cycle Hydroxyurea
S- specific antimetabolite
41
Indications of Hydroxyurea (5)
CML Blast Crisis (to lower blast count given with radiotherapy: Head and neck CA Essential thombocytosis Polycythemia Vera
42
AE of Hydroxyurea (4)
BMS, Nadir: 6-7 days after tx Mucositis Inc lethargy Maculopapular rash
43
when plasma conc. max of hydroxyurea?
1 hr, excreted unchanged by kidneys well absorbed orally even in high dose
44
MOA of Vinca alkaloids?
Binds to α & β tubulin subunits -> prevents polymerization -> cell arrest (metaphase)
45
Vinblastine indication (3)
Testicular CA, Hodgkin's Lymphoma & Bladder CA
46
What are the Vinca Alkaloids? (3)
Vinblastine, Vincristine & Vinorelbine
47
AE of Vinblastine (3)
DLT (Leukopenia 6-7 after tx) (reversible) Mucositis (high dose) Vesicants (Blister agent)
48
Metab of Vinblastine
Liver (CYP450) dos adj required in liver dysfunction
49
Route of administration of Vinblastine
IV only
50
Vincristine Indication (3)
ALL, Lymphoma, Wilms tumor
51
Vincristine AE (1 early 4 late signs)
early signs of toxicity DLT-> peripheral neuopathy (paresthesia of distal fingers) late signs of toxicity Decrease in motor strength (dorsiflexion of the foot) Constipation, Alopecia SIADH
52
Vinorelbine Indications (2)
Non-small cell lung CA, Breast CA
53
Vinorelbine AE (3)
DLT (neutropenia) nadir: 7-10 days recovery: 14 days Mild sensory neuropathy, stomatitis GI toxicity : constipation
54
Vinorelbine other use/ important info
Non-specific inhibitor of AZT (Azidothymidine/Zidocudine) (Tx for AIDS kaposi sarcoma)
55
Taxanes MOA
Binds to β tubulin subunit > stabilization of microtubule > inhibition of depolymerization
56
What are the Taxanes? (2)
Paclitaxel, Docetaxel
57
What phase are the taxanes?
M phase specific agents
58
Paclitaxel Indication (5)
Ovarian, Breast, head and neck, esophageal, non small cell CA - upper body
59
Paclitaxel AE (3)
If formulated in castor oil + alcohol (Cremophor EL) Histamine stimulated acute hypersensitivity (needs antihistamine / steroids) Neutropenia, transient bradycardia, heart block, ischemia (cardiotoxicity)
60
Importance of paclitaxel (3)
Prototype drug Insoluble in aqueous solution IV bolus or continuous administration
61
Docetaxel Indication (4)
ANTHRACYCLINE RESISTANT ADVANCED BEAST CA, non small cell lung CA, ovarian, head and neck CA
62
Docetaxel AE (6)
does NOT use cremaphor EL (castor oil + alcohol) = less toxic SEVERE neutropenia, severe asthma, peripheral neuropathy, stomatitis, myalgia
63
Importance of Docetaxel (3)
Sister drug of paclitaxel Soluble in aqueous solution IV only
64
Metab of Taxanaes
Liver
65
Topoisomerase 1 inhibitor MOA
induction of single stranded breaks -> inhibition of DNA synthesis
66
Function of Topoisomerase 1
Repairs/relaxes simple coils by repairing single strand breaks -> DNA synthesis
67
What phase does topoisomerase 1 inhibitor act on?
S phase specific agent
68
What are the topoisomerase 1 inhibitors? (2)
Irinotecan, Topotecan
69
Irinotecan Indication (2)
Advanced colorectal CA, Colon CA
70
Irinotecan AE (3-4)
DIARRHEA, nausea/vomiting Alopecia, headache
71
Route of administration of Irinotecan
IV only
72
Metab of irinotecan
Hepatic & Biliary
73
Topotecan Indication (3)
Advanced colorectal CA, refractory ovarian CA, Small cell lung cancer
74
Topotecan AE (1)
DLT; Myelosuppression
75
Route of administration of Topotecan
IV only
76
Metab of Topotecan
Biliary
77
Topoisomerase 2 inhib MOA
induction of double strand break -> prevent religation of DNA -> induces apoptosis
78
Function of Topoisomerase 2?
Repairs supercoiling of DNA
79
What are the topoisomerase 2 inhibitors? (2)
Etoposide, Teniposide
80
Indication of TI2 inhib (5)
HODGKIN'S disease Lymphomas Leukemias SCLC Testicular CA
81
AE of TI2 inhibs (6)
MYELOSUPPRESION Hypotension with rapid infusion (given slowly) Alopecia (10-30%) GI toxicity (10-20%) inc ALT AST Leukemogenic with no preceding Myelodysplastic syndrome
82
What phase of cell cycle are TI2 inhibs?
Late S-G2 Phase specific agents
83
Where is TI2 inhibs extracted from?
Mayapple root (Podophyllum peltatum)
84
route of administration of Etoposide?
IV,PO
85
route of administration of Teniposide?
IV only
86
Metab of Etoposide?
Hepatic
87
Metab of Teniposide?
Hepatic, Renal
88
What are the classical alkylating agents? (4)
Cyclophosphamide Ifosfamide Melphalan Chlorambucil
89
Classical Alkylating agents are under what?
Cell cycle Nonspecific Agents
90
Cyclophosphamide MOA
Inhibition of DNA replication and RNA transcription -> Inhib of nucleic acid synthesis Becomes 4-hydroxycyclophosphamide in healthy cells: converted to INACTIVE metabolites In cancer cells: Aldophosphamide converted into phosphoramide mustard (anticancer)
91
Metabolites of Cyclophosphamide? (2)
Phosphoramide Acrolein (Hemorrhagic cystitis)
92
Indication of Cyclophosphamide
Lymphoma (SALVAGE CHEMOTHERAPY) (NOT FIRST LINE) Breast CA, SCLC, Ovarian CA, BM transplantation, immunosuppresion
93
What is the antidote for hemorrhagic cystitis?
MESNA
94
What dose causes nausea and vomiting in cyclophosphamide?
>500mg 8-12 hours after tx Cyclophosphamide metab -> emetogenic metabolites
95
Cyclophosphamide AE (5-8)
DLT myelosuppression nadir 10-14 days, recover 21 days Hemorrhagic cystitis (hematuria) Nausea and vomiting Pulmonary fibrosis, acute hemorrhagic carditis, alopecia, SIADH, Veno occlusive disease of liver Long term: Infertility and 2ndary malignancies
96
Ifosfamide MOA
Inhibition of DNA replication and RNA transcription -> Inhibiion of nucleic acid function
97
Ifosfamide Indication (3)
Lymphoma (SALVAGE CHEMOTHERAPY) Breast and ovarian CA, Sarcoma, Testicular CA
98
Ifosfamide AE (5-8)
DLT myelosuppression nadir 10-14 days, recover 21 days Hemorrhagic cystitis Nausea and vomiting Pulmonary fibrosis, acute hemorrhagic carditis, alopecia, SIADH, Veno occlusive disease of liver Long term: Infertility and 2ndary malignancies
99
Melphalan MOA
Formation of intra strand, inter strand DNA + cross links
100
Melphalan Indication (4) + Combination (3)
Multiple myeloma (prednisone, thalidomide, bortezomib) Myeloablative conditioning regimen for BM transplant Ovarian CA, Breast CA
101
Chlorambucil MOA
Forms DNA cross links resulting in inhibtion of DNA synthesis and function
102
Chlorambucil Indication (2)
CLL, low grade non-hodgkin's lymphoma
103
Chlorambucil AE (5)
DLT, Liver abnormalities, Pulmonary fibrosis, Secondary malignancies and leukemia Well tolerated
104
What are the non-classical alkylating agents? (2)
Dacarbazine, Procarbazine
105
Dacarbazine MOA
followns intramolecular cyclization Imidazole carboxamide forms methylcarbonium ion -> attacks N7 guanine
106
Dacarbazine Indication (3)
Hodgkin's disease Soft Tissue sarcoma Malignant Melanoma
107
Dacarbazine AE (5)
Emetogenic, Myelosuppresion Flu-like symptoms Facial FLUSHING severe pain and necrosis in extravasation (phlebitis, cellulitis)
108
Route of administration Dacarbazine
IV only
109
Half life of Dacarbazine
5 hrs
110
Metab of Dacarbazine
Liver
111
Route of elim (Dacarbazine
Urine as diazomethane
112
MOA of Procarbazine
Inhibits transfer of methyl groups of methionine in the RNA -> prevents DNA, RNA and protein synthesis
113
Indication of Procarbazine (4)
Hodgkin's disease Non-hodgkin's disease Lung and Brain CA
114
Procarbazine AE (3)
GI toxicity Neurotoxicity Severe headache due to MAO inhibitor
115
What is Thiotepa's drug classification
Akyl-alkaline sulfonate based akylating agent
116
Thiotepa MOA
Formas DNA cross links -> inhibition of DNA synthesis
117
Thiotepa indication (5)
Superficial bladder CA, BM transplantation, Brain tumor, Breast CA, Ovarian CA
118
AE of Thiotepa (5)
Myelosuppresion (DLT) AT high dose: Mucositis, Skin rash, CNS toxicity Gonadal dysfunction
119
Thiotepa is a blister agent
False
120
Procarbazine metabolite
azoprocarbazine causes DNA scission
121
Route of administration of Procarbazine
Oral only
122
Half life of procarbazine
10 mins
123
Route of elim of Procarbazine
urine
124
What are all the platinum compounds? (3)
Cisplatin, Carboplatin, Oxaliplatin
125
Platinum compounds MOA
Forms platinum coordination complex -> creates interstrands in DNA -> inhibition of DNA synthesis
126
What are the binding sites of platinum compounds? (3)
Primary: N7 N3 position of adenine O6 position of cytosine
127
What phase of the cell cycle do platinum compounds affect?
All stages
128
What generation is Cisplatin?
1st
129
Cisplatin indications (4)
Broad range solid tumors, Ovarian CA, Testicular CA, Lung CA, head and neck CA
130
Cisplatin AE (6)
DLT: Nephrotoxicity -> Renal failure Caution with inc creatinine Hypomagnesemia, Severe N&V, Anemia, Hypersensitivity Neurotoxicity= Hearing loss
131
Antidote of Cisplatin?
Amifostine
132
Combination regimen for non seminomatous CA
Cisplatin
133
Carboplatin Generation
2
134
AE of carboplatin
DLT; Myelosuppresion
135
What's the difference of Carboplatin with Cisplatin?
Carboplatin has bidentate ligand instead of 2 Cl ligands in cisplatin
136
Oxaliplatin Generation
3
137
Oxaliplatin indication (1)
2nd line therapy for metastatic colorectal CA
138
Oxaliplatin AE (3)
DLT; Neurotoxicity -> numbness Intense pain and hypersensitivity of temp to both hands and feet Less nephrotoxic
139
Unique characteristic of Oxaliplatin?
bidentate oxalate group
140
What are the Antitumor antibiotics? (4)
Anthracyclines, Bleomycin, Dactinomycin, Mitomycin
141
Anthracycline suffix?
-rubicin
142
Anthracycline MOA
Intercalation of DNA to formation of free radicals High affinity binding to DNA from intercalation -> inhibits TI2 Generates semiquinone free radicals and oxygen free radicals Alter's fluidity and transport of the cell membrane
143
Anthracycline Indications (8)
AML, ALL, Hodgkin's disease, Non-Hodgkin's disease, Lymphoma Breast, Lung, Bladder CA
144
Anthracycline AE (3)
Most important and dreaded SE: DLT (Cardiac toxicity) Acute - Arrythmia, Conduction Abnormalities/ECG changes Chronic - Dilated cardiomyopathy (when given 450-550mg of daunorubicin) Adriamycin Flare Radiation Recall Reaction
145
What's the Antidote for Anthracycline DLT?
Dexrazoxane -Iron chelating agent -Started with > 300 mg -slow infusion -requires cardiac monitoring AE: Pain in injection site, neutropenia, thrombocytopenia
146
Route of administration for Anthracycline:
IV only (inactivated in the GIT
147
Does anthracycline penetrate BBB?
No
148
Anthracycline important side effects (2)
Cardiac toxicity DLT and imparts discoloration of urine
149
Half life of Anthracycline (2)
Distribution phase: 15 mins Elimination phase: 24-48 hours
150
Metab of anthracycline
Liver (Daunomycin/Daunorubicin & Doxorubicinol)
151
Excretion of Anthracycline
Bile
152
Which anthracyclines are less toxic to the heart? (2)
Epirubicin and Idarubicin
153
MOA of Bleomycin
Oxidation of DNA-Bleomycin-ferrous complex -> production of free radicals -> single and double stand break -> inhibition of DNA synthesis
154
What type of agent is Bleomycin?
Copper chelating glycopeptide
155
Bleomycin Indication (6)
Hodgkin's disease, Non-Hodgkin's Lymphoma, Germ cell tumors, head and neck CA SCC of the skin cervix and vulva, pleural effusion/ascites
156
AE of Bleomycin (2)
DLT; Pulmonary Fibrosis Pneumonitis
157
What specimen is Bleomycin derived from?
Streptomyces verticullus
158
Route of administration of Bleomycin (4)
SC,IM,IV & intracavitary
159
Antidote for Bleomycin
Bleomycin hydrolase
160
Conc. of bleomycin hydrolase from highest to lowest (4)
Liver, spleen, lungs, skin
161
Dactinomycin MOA
Binds to DNA through INTERCALATION to GUANINE-CYTOSINE base pairs -> dacti DNA complex -> inh of DNA dependent rna synthesis
162
Indications of Dactinomycin (4)
Choriosarcoma Wilms Tumor Testicular CA Ewing's Sarcoma
163
AE of Dactinomycin (3)
BMS, NV, DLT; Leukopenia & Thrombocytopenia (7 days tx)
164
Half life of Dactinomycin
36 hrs
165
Route of administration of Dactinomycin
IV
166
Elimination of Dactinomycin
Renal
167
Does Dactinomycin pass the BBB?
No
168
What specimen is Dactinomycin extracted from?
Streptomyces parvulus
169
Mitomycin MOA
Cross links DNA strands = DNA synthesis inhibition
170
Indications of Mitomycin (4)
tx of solid tumors: Lungs Pancreas Stomach Head and neck
171
What are the specific toxic doses of Mitomycin?
>30 mg = pulmonary fibrosis >50 mg = HUS (Hemolytic uremic syndrome >70mg = nephrotoxicity
172
Normal adverse effects of Mitomycin?
DLT; myelosuppression (occurs 3-5 days after tx) REcovery (6-8 wks)
173
What type of antibiotic is Mitomycin?
Quinine Antibiotic
174
What is the half life of Dactinomycin?
25-90 mins
175
Route of administration of Dactinomycin
IV
176
What drug is under "Enzymes"?
L-Asparaginase
177
MOA of L-Asparaginase?
Convertion to aspartic acid +ammonia = depletion of L asparagine and inhibition of protein synthesis > compromise of cell function = cell death
178
Indication of L-Asparagine (3)
ALL T-Cell leukemia T-Cell lymphomas
179
What is the MAIN AE of L-Asparagine?
Hypersensitivity reaction = skin testing required prior to administration
180
Non important AE of L-Asparginase (4)
Neurologic toxicity Hyperglycemia altered production of coagulation factions (inc bleeding) Acute hemorrhagic pancreatitis
181
What specimen is L-Asparaginase isolated from? (2)
E. coli & Erwina carotovora
182
Effect of PEGylated asparaginase
Dec antibody formation and inc serum half life
183
Adverse effect of PEGylated asparaginase (2)
immunologic sensitization to foreign proteins or depletion of asparagine pools and inhibition of protein synthesis
184
Estrogen based Antineoplastic
Diethystilbestrol
185
MOA of Diethystilbestrol
LH production to inhibit growth of prostatic tissue
186
Indication of Diethystilbestrol (1)
Prostatic CA
187
Diethystilbestrol Contraindications (1)
Breast CA
188
Diethystilbestrol AE; Acute (2) Chronic (3)
Acute: Females (NV hyperglycemia, uterine bleeding Males (loss of muscle, inc body fat loss of libido) Chronic: Hypercoagulability Premature cornary disease Feminization
189
Anti-estrogen based Anti-neoplastic
Tamoxifen
190
MOA of Tamoxifen
Binds to estrogen receptor in cancer cell & tissue targets
191
Indication of Tamoxifen (1)
Breast CA
192
AE of Tamoxifen; Acute (3) Chronic (3)
Acute: Hot flushes, weight gain, nausea, vaginal dryness, loss of libido Chronic: Thromboembolic disease, Retinitis, Endometrial CA, Hepatotoxicity
193
Androgen base antineoplastic (3)
Testosterone Propionate Fluoxymesterone, Testosterone enanthate
194
Androgen based antineoplastic MOA:
Direct physiologic effect on androgen receptor
195
Indication of Androgen based antineoplastic (2)
Metastatic breast CA w/ hormone receptor (+) disease BM stimulants in BM failure syndromes
196
Contraindication of Androgen based antineoplastic (1)
Prostatic CA
197
Adverse effect of Androgen based antineoplastic; Acute (2) Chronic (1)
Acute Cholestatic jaundice Fluid retention Chronic Virilization (mail hair growth)
198
Anti-androgen based antineoplastic (2)
Flutamide, Bicalutamide
199
Anti-androgen based antineioplastic MOA
Competes with androgens binding to receptors -> blocks action of adrenal or testicular origin -> stimulate growth of malignant and normal prostatic tissue
200
Indication of Anti-androgen based antineoplastic (1)
Early stage and metastatic Prostate Cancer
201
AE of Anti-androgen based antineoplastic (3)
Gynecomastia, Gi distress Liver failure (flutamide) Dec Libido, Hot flushes
202
What is Anti-androgen based antineoplastics combined with? (1)
GnRH
203
Gonadotropine-releasing hormone agonist (2)
Leuprolide and Goserelin
204
MOA of GRHA
Inc LNRH -> stimulation of Pituitary -> inc LH & FSH -> reduction of testicular androgen and ovarian estrogen prod
205
Indication of GRHA (2)
Prostate & Breast CA
206
AE of GRHA ; Acute (1) Chronic (3)
Acute Transient flare of symptoms Chronic Hot flushes, impotence, gynecomastia
207
Aromatase inhibitors (3)
Aminoglutethimide, Exemestane, Anastrozol/ Letrozole
208
Aminoglutethimide MOA
Non-steroidal inhibition of corticosteroid synthesis -> conversion of cholesterol to pregnenolone -> estrogen inhibition of extra adrenal synthesis of estrone from estradiol Androstenedione -> estrone
209
Aminoglutethimide Indications (2)
Prostate CA Breast CA
210
AE of Aminoglutethimide ; Acute (1) Chronic (1)
Acute: Dizziness Chronic Rash
211
Exemestane MOA
Steroidal irreversible aromatase inhibitor Inhibits synthesis of estrogen via inhibition of adrenal androgen conversion to estrogen
212
Exemestane Indication
Breast CA
213
Exemestane AE (4)
Nausea Fatigue Hot flushes Acne Hair changes
214
Anastrozole/Letrozole MOA
Selective non-steroidal aromatase inhibitor with no inhibitory effects in adrenal glucocorticoid synthesis
215
Indication of Anastrazole/Letrozole (1)
Post-menopausal women with metastatic breast CA (FIRST LINE TX)
216
Indication of Anastrozole/Letrozole (1)
Post-menopausal women with metastatic breast CA (FIRST LINE TX)
217
Difference of Anastrozole/Letrozole VS Aminoglutethimide
More potent More selective No need for hydrocortisone No predisposition to endometrial CA No androgenic side effects
218
What are the Glucocorticoids? (3)
Prednisolone, Methylprednisolone, Dexamethasone
219
MOA of Glucocorticoids
Lympholytic & Non myelosuppressive = induces cell death
220
Glucocorticoid Indications (6)
ALL, Lymphoma Multiple Myeloma Breast CA Brain metastasis Spinal cord compression due to malignancy
221
Glucocorticoid AE ; Acute (5) Chronic (4)
Acute- Fluid retention Hyperglycemia Mood changes Hypokalemia Acute Confusional States Chronic- Osteoporosis Immunosuppression GI ulcers Cushingoid appearance, cataracts
222
Progestin based antineoplastic (2)
Megestrol acetate Hydroxyprogesterone
223
Indication of Megestrol acetate/Hydroxyprogesterone (3)
Palliative for metastatic breast CA, Endometrial CA, Prostate CA
224
AE of Megestrol Acetate/Hydroxyprogesterone ; Acute (2) Chronic (2)
Acute Inc appetite fluid retention Chronic Weight gain Thromboembolism
225
Route of Administration of Progestin based antineoplastic
IM
226
What category is Farsenyl Transferase inhibitors and MOA
Targeted chemotherapy Inhibits tumor cell growth by inhibiting farnesyl transferase
227
Important information of Farsenyl Transferase (3)
Mutant RAS is constitutively active (found in 30% of cancer cells) RAS signaling requires linking RAS to inner membrane leaflet -> adding a carbon by the farsenyl transferase Potent inhibitors of tumor cell growth
228
What are the Tyrosine Kinase Inhibitors (8) *-tinibs
Imatinib/Gleevec Dasatinib/Sprycel Nilotinib/Tasigna Gefitinib/Iressa Erlotinib/Tarceva Lapatinib/Tykerb Sorafenib/Nexavar Sunitinib/sutent
229
Protease Inhibitor antineoplastic
Bortezomib
230
Bortezomib MOA
Inhibits proteasome leads to accumulation of regulatory protein (Bax) which leads to cell crisis and apoptosis
231
Bortezomib Indication (2)
Multiple myeloma Plasma cell disorder
232
Bortezomib Important info (skip me)
Elevated levels of fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) associated with angiogenesis VEGF is regulated by multiple cytokines IGF-1R PKB C-SRC tyrosine kinase Inositol triphosphate kinase
233
What antineoplastic is under Matrix metalloproteinase inhib
Marimastat
234
Marimastat indication (1)
Pancreatic CA
235
Marimistat important info (skipme)
MMPS comprise of collegenases, gelatinases, stromelysins and membrane type (MT) Collagenase cleaves glycine and isoleucine
236
What are the immunotherapy agents? (2)
Monoclonal Antibodies Car T Cells
237
Indications of Moloclonal Antibody (1)
Cancer Immunotherapy
238
MOA of Monoclonal Antibody
Serve as substitue antibodies that can restore, enhance or mimic the immune systems attack on cancer cells Cytotoxic Lymphocyte associated antigen 4 (CTLA4) inhibitor e.x IPILIMUMAB ; functions as a signal dampener to upregulate T-cells against tumor cells Programmed cell death protein 1 inhibitor (PD1); activates T- cell function against tumor cells
239
Car T Cells MOA
Guides T cell directly to the tumor Triggers T cells fighting power to attack the cancer cells
240
Car T cells Indication
Refractory ALL Non-Hodgkin's Lymphoma (Diffuse large B cell lymphoma)
241
Car T Cells AE (2)
Cytokine Storm Autoimmune disease manifesting as colitis or neurotoxicity

Pharma (2 decks)

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