Pharmacology Of Neoplasias Flashcards
(91 cards)
1
Q
MOA of Alkylating Agents
A
Alkylation interferes with DNA replication which results in cell death. Cell cycle non-specific.
2
Q
4 Classes of Alkylating Agents
A
- Nitrogen mustards
- Nitrosoureas
- Platinum analogs
- Non-classic alkylating agents
3
Q
Drugs in Nitrogen Mustard class of Alkylating Agents (6)
A
- Mechlorethamine, Melphalan
- Cyclophosphamide, Ifosfamide
- Chlorambucil
- Thiotepa
- Busulfan
- Altretamine
Note: Chemoprotective agent - 2% sodium thiosulfate solution - creates water soluble compound for elimination. Addition of a phenyl ring can also decrease reactivity by slowing aziridinium.
4
Q
Drugs in the Platinum Analog class of Alkylating Agents (2)
A
- Cisplatin, Carboplatin
- Oxaliplatin
* These drugs form intra-strand cross-links
5
Q
MOA of Vinca Alkaloids
A
Binds to tubulin (tubulin is the precursor of microtubulin which is necessary for cell division). M-phase specific.
6
Q
Drugs in the Vinca Alkaloids class (3)
A
- Vincristine
- Vinorelbine
- Vinblastin
7
Q
MOA of Taxanes
A
Enhance tubulin polymerization which alters normal tubulin function, preventing cell division. M-phase specific.
8
Q
Drugs in the Taxanes class (2)
A
- Paclitaxel
2. Docetaxel
9
Q
MOA of Antimetabolites
A
Inhibits enzymes necessary for DNA, RNA or protein synthesis.
10
Q
3 classes of Antimetabolites
A
- Folic acid antagonists
- Purine antagonists
- Pyrimidine antagonists
11
Q
Drugs within the Folic Acid Antagonists class of Antimetabolites (3)
A
- Methotrexate: directly inhibits dihydrofolate reductase (DHFR) and indirectly inhibits thymidylate synthase.
- Pemtrexed
- Pralatrexate
12
Q
Drugs within the Purine Antagonists class of Antimetabolites (4)
A
- 6-Mercaptopurine: (ADRs = hepatotoxicity; elevated liver enzymes)
- Cladribine
- Fludarabine
- Pentostatin
Note: Thiopurines are metabolized by thiopurine methyl transferase (TPMT)
13
Q
- ADR of Fludarabine
2. ADR of Cladribine
A
- Cough
2. Stomatitis
14
Q
Drugs in the Pyrimidine Antagonists class of Antimetabolites (4)
A
- 5-Fluorouracil
- Capecitabine
- Cytarabine
- Gemcitabine
15
Q
ADR of Cytarabine
A
Hand and Foot Syndrome
16
Q
Drugs in the Antibiotics class (4)
A
- Bleomycin
- Dactinomycin
- Anthracyclines
- Mitomycin C
17
Q
MOA of Bleomycin
A
Binds to iron, creates free radicals, results in DNA strand breaks. G2-phase specific.
18
Q
MOA of Dactinomycin
A
Inhibits RNA polymerase, binds to DNA.
19
Q
MOA of Anthracyclines
A
Intercalate into DNA, free radical formation, topoisomerase II inhibitors.
20
Q
Drugs in the Miscellaneous Agents class (3)
A
- L-asparaginase
- Arsenic trioxide
- Hydroxyurea
21
Q
MOA of L-asparaginase
A
Enzyme that breaks down L-asparagine, depleting asparagine in cancer cells that cannot produce the amino acid.
22
Q
MOA of Arsenic Trioxide
A
Inhibits telomerase activity to cause apoptosis and causes DNA strand breaks. Dactinomycin related to this drug.
23
Q
MOA of Hydroxyurea
A
Inhibits Ribonucleotide reductase. S-phase specific.
24
Q
Drugs in the Topoisomerase I Inhibitors class (2)
A
- Irinotecan
2. Topotecan
25
MOA of Topoisomerase I Inhibitors
Inhibitor of topoisomerase I. S-phase specific.
26
Drugs in the Topoisomerase II class (4)
1. Etoposide
2. Teniposide
3. Anthracyclines (Doxorubicin, daunorubicin, idarubicin, epirubicin)
4. Mitoxantrone
27
MOA of Topoisomerase II Inhibitors
Inhibits complexes with DNA and the enzyme topoisomerase II, which results in DNA strand breaks. S-phase specific.
28
ADRs of Alkylating Agents (1)
Extravasation
29
ADRs of Cisplatin (5)
1. Severe nausea and vomiting
2. Electrolyte imbalances
3. Nephrotoxicity
4. Ototoxicity
5. Peripheral neuropathy
30
ADRs of Anthracyclines [Daunorubicin, doxorubicin] (3)
1. Alopecia
2. Mucositis
3. Acute and cumulative cardio toxicity (irreversible CHF)
There is a total lifetime dose limit due to these side effects.
Note: Should be treated with a chemoprotective agent- iron chelator (dexrazoxane).
Mitoxantrone is a synthetic agent related to Anthracyclines that does NOT generate free radicals and avoids cardio toxicity.
31
ADR for Topoisomerase II Inhibitors
Mucositis
32
ADRs of Methotrexate and 5-fluorouracil (3)
1. Mucositis (mouth sores and diarrhea)
2. Photosensitivity
3. Nephrotoxicity
33
ADRs of Bulsulfan and Bleomycin
Pulmonary fibrosis
34
ADRs of Cyclophosphamide and Ifosfamide
Hemorrhagic cystitis
Note: These prodrugs are metabolized to the form acrolein which is urotoxic. Hydration and co-administration with Mesna (chemoprotective agent) can minimize the effects of acrolein.
35
ADRs of Vinca Alkaloids and Taxanes (3)
1. Alopecia
2. Neurotoxicity
3. Peripheral neuropathy
36
ADRs of Iriontecan
Acute and delayed diarrhea
37
What 2 substances are responsible for stimulating platelet aggregation?
1. Thromboxane A2 (TxA2)
| 2. ADP
38
MOA of aspirin
Irreversibly inhibits COX-1 and COX-2 in platelets. Also inhibits TxA2 and reduces platelet aggregation.
39
Indications for aspirin
Thromboembolic disorder, osteoarthritis, RA, fever, pain, prophylaxis for stroke and MI.
40
ADRs for aspirin (6)
1. GI discomfort
2. Tinnitus
3. GI ulcer/bleed
4. Hemorrhage
5. Reye’s syndrome (usually seen in children recovering from a viral infection that was treated with aspirin)
6. Possible allergic reaction (hypersensitivity)
41
Difference between COX-1 and COX-2 as pharmacology targets?
COX-1 inhibitors (aspirin, ibuprofen) will inhibit or decrease platelet aggregation; aspirin has a 53% greater platelet inhibitor effect in comparison to ibuprofen.
Selective COX-2 inhibitors have NO platelet effect.
42
3 drugs that act as anticoagulants
1. Heparin
2. Factor Xa Inhibitors
3. Warfarin
43
MOA of Heparin (HMW: high molecular weight) and Enoxaparin (LMW: low molecular weight)
Enhances actions of the protease Anti-thrombin III, which inactivates thrombin and Factor X, slowing the clotting cascade
44
Indications for Heparin and Enoxaparin
Anticoagulant therapy and thromboembolic disorders
45
ADRs for Heparin and Enoxaparin (4)
1. Hemorrhage
2. Easy bruising
3. GI bleed
4. Heparin-induced thrombocytopenia (autoimmune activation and destruction of platelets)
46
Considerations for Heparin and Enoxaparin
1. Unfractionated Heparin (HMW) effectively catalyzes the inactivation of both Thrombin and Factor Xa
2. Enoxaprin increases inactivation of Factor Xa and has LESS of an effect on Thrombin
3. Protamine sulfate can reverse the effects of heparin
47
Rivaroxaban and Apixaban are inhibitors of ______ ___.
Factor Xa
48
Indications for Rivaroxaban and Apixaban
Treatment or prophylaxis for DVT
49
ADRs of Rovaroxaban and Apixaban
1. Hemorrhage
2. Easy bruising
3. GI bleed
50
Considerations for Rivaroxaban and Apixaban (3)
1. Given as a fixed dose and no monitoring is required
2. More rapid onset and shorter half-life than warfarin
3. Andexanet alfa approved as a reversal agent for Xa inhibitors in 2018
51
MOA of warfarin
Inhibits liver Vitamin K Reductase: inhibits regeneration of Vitamin K, an essential cofactor for synthesis of clotting factors in the liver: factors II, VIII, IX, and X
52
Warfarin pharmokinetics considerations
Genetic variants in:
1. CYP2C9 will cause varying rates of drug activity as warfarin is metabolized by this enzyme
2. Vitamin K epoxide reductase (VKOR) will cause varying responses to warfarin
53
ADRs of warfarin (2)
1. Hemorrhage
| 2. GI bleed
54
Warfarin considerations (5)
1. Reversal agents: Vitamin K, fresh-frozen plasma, three- or four-factor prothrombin complex concentrate
2. Should be monitored regularly by PTT and INR
3. Highly protein bound and may interact with other medications (aspirin, NSAIDs)
4. Metabolized by CYPs and should be used with caution with other CYP inducers or inhibitors
5. Avoid foods high in Vitamin K (collard greens, kale, spinach)
55
Allopurinol (Xanthine Oxidase Inhibitor) MOA
Inhibits xanthine oxidase, which converts hypoxanthine to xanthine and xanthine to uric acid; decreased uric acid levels lead to reduced urate crystal formation
56
ADRs of Allopurinol (5)
1. Pruritus
2. Rash
3. GI upset
4. Agranulocytosis
5. Aplastic anemia
57
Ruxolitinib (Tyrosine Kinase Inhibitor) MOA
A kinase inhibitor which selectively inhibits JAKs 1 and 2: particularly targets dysregulated JAK signaling associated with myelofibrosis and polycythemia vera and their unregulated cell proliferation.
58
ADRs of Ruxolitinib (7)
1. Edema
2. Bruising
3. Dizziness
4. Headache
5. Anemia
6. Herpes zoster
7. Hepatitis
59
Pegylated interferon alpha MOA
Enhances host immune system to increase activated T lymphocytes, NK cells, and macrophages
60
ADRs of Pegylated interferon alpha (4)
1. Fever
2. Headache
3. Chills
4. Generalized aches and pains
61
MOA of Hydroxyurea
Inhibits ribonucleotide reductase and inhibits DNA synthesis
62
Indications for hydroxyurea
Sickle cell anemia, essential thrombocythemia, polycythemia vera
63
ADRs of hydroxyurea (7)
1. Nausea/vomiting
2. Myelosuppression
3. Neutropenia
4. Decreased platelet count
5. Decreased reticulocyte count
6. Lower extremity ulcers
7. Skin cancer risk
64
Prednisone and methylprednisolone MOA
Anti-inflammatory corticosteroids with potent glucocorticoid and weak mineralocorticoid activity.
Broad range of active inhibition against multiple cell types and mediators involved in inflammation.
65
ADRs of prednisone and methylprednisolone (8)
1. Infections, striae, delayed wound healing
2. Osteopenia, osteoporosis
3. Adrenal insufficiency
4. Avascular necrosis
5. Weight gain
6. Insomnia
7. Mood changes, delirium
8. Cataracts, glaucoma
66
MOA of low-dose thalidomide
Exhibits immunomodulatory and anti-angiogenic characteristics; immunologic effects mary vary based on conditions
TERATOGENIC
Pregnancy Category: X
67
ADRs of low-dose thalidomide (2)
1. Nausea/vomiting
| 2. Fatigue
68
Treatments of erythromelalgia of Essential Thrombocytosis (ET)
1. COX-1 inhibitors (aspirin, ibuprofen)
| 2. If no response to salicylates, hydroxyurea, pegylated interferon alpha, or anagrelide
69
MOA of Anagrelide
A phosphodiesterase-3 enzyme (PDE-3) inhibitor that inhibits platelet aggregation and causes a dose-related reduction in platelet production
70
ADRs of Anagrelide (6)
1. Headache
2. Edema
3. Diarrhea
4. Palpitations
5. Prolonged QT interval
6. Hemorrhage
71
ALL induction treatment regimen (2):
1. Vincristine + glucocorticoid + anthracycline +/- pegaspargase
2. If Ph+, add imatinib or another tyrosine kinase inhibitor if resistant to imatinib
72
ALL CNS prophylaxis goal of therapy
Eradicate undetectable leukemia cells in CNS and minimize neurotoxicity
73
ALL CNS prophylaxis treatment
Intrathecal methotrexate +/- cranial irradiation
74
ALL Maintenance Therapy
12-week course of POMP regimen
| Purinethol, Oncovin, Methotrexate, Prednisone
75
Relapsed ALL Treatment
Blinatumomab is a monoclonal antibody that binds to both CD19 (an antigen present during B cell development) and CD3 (T-cell receptor), which results in lysis of CD19 cells
76
Rituximab (CD20 antibody) MOA and Indications
Targets CD20 found on surface of normal and malignant B cells. Binds to CD20 and recruits immune effector functions to mediate B-cell lysis (via CDC and ADCC) and cause apoptosis.
Used to treat Non-Hodgkin’s Lymphoma and CLL.
77
ADR of Rituximab
Steven-Johnson Syndrome
78
AML Post-remission Therapy
Purine Antagonists of Antimetabolites: Fludarabine, Cladribine, Clofarabine (adenosine analogs).
DNA polymerase and chain elongation inhibitors.
79
Acute Myeloid Leukemia (AML) Induction Treatment
Pyrimidine Antagonists of Antimetabolites: Cytarabine and gemcitabine (cytidine analogs).
DNA polymerase and chain elongation inhibitors.
80
Dasatinib (Tyrosine Kinase Inhibitor) MOA and Indications
Targets multiple defective tyrosine kinases (SRC tyrosine kinase, platelet-derived growth factor receptor, BCR-ABL, C-KIT kinase).
More potent inhibitor of ABL than imatinib.
Has activity against imatinib-resistant leukemia.
Used for Philadelphia chromosome positive CML (Ph+CML) and ALL (Ph+ALL).
81
ADRs of Dasatinib (2)
1. Edema and pleural effusion
| 2. Hemorrhage
82
Nilotinib (Tyrosine Kinase Inhibitor) MOA and Indications
BCR-ABL selective tyrosine kinase inhibitor. Acts as a competitive inhibitor of the ATP-binding site of BCR-ABL. Inhibits cellular proliferation and induces apoptosis.
Higher affinity for BCR-ABL than imatinib and dasatinib.
Used for Ph+CML.
83
ADR of Nilotinib
Electrolyte abnormalities
84
Hodgkin’s Lymphoma Treatment Overview
ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine)
85
Brentuximab vedotin MOA and Indications
Targets CD30 found on Hodgkin’s Lymphoma and Anaplastic Large Cell Lymphoma (ALCL)
86
ADRs of Brentuximab vedotin (4)
1. Neutropenia
2. Peripheral neuropathy
3. Fatigue
4. Nausea/vomiting/diarrhea
5. Anemia
6. URIs
87
Non-Hodgkin Lymphomas Indolent Subtype Treatment
Not curable with chemotherapy.
| Bendamustine: DNA alkylation and antimetabolite (S-phase specific). ADR = increased bilirubin levels.
88
Non-Hodgkin Lymphomas Aggressive Subtype Treatment
Potentially curable with chemotherapy.
89
Non-Hodgkin Lymphomas Highly Aggressive Subtype Treatment
Potentially curable with chemotherapy
95
Imatinib (Tyrosine Kinase Inhibitor) MOA and Indications
Inhibition of proliferation which results in apoptosis.
| Used to treat BCR-ABL mutation in CML, GI stromal tumors, and platelet-derived growth factor receptor mutations.
96
ADRs of Imatinib (4)
1. Nausea/vomiting
2. Edema
3. Arthralgia/myalgias
4. Myelosuppression
