Oncology Pharmacology Flashcards
Azathioprine (imuran)
AZa, immunosuppressant medication used in organ transplantation and to treat autoimmune disorders
Methotrexate
Ok
Fluorouracil (5-FU)
Antimetabolite medication which works by inhibiting thymidylate synthase, leading to decreased DNA synthesis.
Indications flor 5-FU
Slow growing solid tumours
What is 5-FU coadministered with to treat gastric adenocarcinoma
Leucovorin
Why may 5-FU be used topically
Nasal cell carcinoma
Side effects fluorouracil
Myelosuppression, which is not reversible with leucovorin, as it is with methotrexate
MOA 5-FU
Antimetabolite that interferes with the cells normal metabolic functioning, inhibiting DNA synthesis. It is a pyramidine analog which competes with thymidylate synthetase to inhibit DNA synthesis
5-FU is a pyramidine analog
Causes thymidylate less death.
It decreases dTMP, as 5-FU competes with dUMP for thymidylate synthase, inhibiting its action.
Blocks synthesis of the pyramidine thymidine which is a nucleoside required for DNA synthesis and replication.
Without DNA synthesis
Tumor cells undergo apoptosis
Indications for 5-FU
Slow growing solid tumors (with leucovorin for stomach cancer)
Basal cell carcinoma (topical)
Examples of slow growing solid tumours
Stomach, colorectal, breast, ovarian, pancreatic
Side effects 5-FU
Myelosuppression —> megaloblastic anemia, neutropenia, and thrombocytopenia
Mucositis-inflammatory lesions of mucosa in oral, nasal and alimentary tract
Severe diarrhea-GI mucositis
Is myelosuppression of 5_FU with lev reversible
No
Is myelosuppression with methotrexate reversible
Yup
Bleomycin
Antitumour antibiotic which is used to treat testicular cancer and Hodgkin lymphoma, and squamous cell carcinoma
MOA bleomycin
Inducing free superoxide and hydroxide radicals, which cleave DNA, leading to breaks in cancerous DNA strands.
Side effects bleomycin
Pulmonary fibrosis, skin changes, and mucositis
Indications for bleomycin
Testicular cancer (germ cell tumours) Hodgkin lymphoma
For treating testicular cancer,what is bleomycin typically combined with
Etoposide and cisplatin bc they have complimentary effects on inhibiting cancerous DNA
For Hodgkin lymphoma what are the drug regimes
ABVD or BEACOPP
MOA bleomycin
Chelates metal ins , leading to pseudoenzyme which converts oxygen to superoxide and hydroxide free radicals which can cleave DNA
break DNA strands (incision too)
Side effects bleomycin
Pulmonary fibrosis (also oxygen toxicity which may play a role in lung injury)
Skin changes (rash, alopecia, hyperpigmentation, and rayneuads, dermatographism)
Mucositis (typically mouth)
Actinomycetes (actinomycetes D)
Antitumour antibiotic for childhood tumours.
Indication for dactinomycin
Wilms, Ewing sarcoma, rhabdomyosarcoma, and gestational trophoblastic malignancy
MOA dactinomycin (actinomycetes D)
Intercalated DNA, halting the replication process in tumors.
Bind DNA transcription initiation complex, preventing RNA chain elongation.
Gets in the way physically blocking DNA replication
Side effect dactinomycin
Myelosuppression->leading to decreased red and white blood cell production
Doxorubicin (adriamycin)
Anthracycline antibiotic used in cancer therapy.
MOA doxorubicin
Intercalating DNA, preventing new cell growth in tumors, but leads to heart damage
Side effects doxorubicin
Cardiotoxic
How can you decrease cardiotoxic side effects of doxorubicin
Give with dexrazoxane
Indications for doxorubicin
Solid tumors (bladder, breast, stomach, ovaries, lungs, thyroids, soft tissue sarcomas) Lymphomas and leukemia’s (leukemia’s and hodgkins)
MOA doxorubicin
Increases free radical production in tumor cells, leading to cytotoxicity
-inhibits biosynthesis of new cells as it intercalated DNA (once topoisomerase has split the DA to be replicated, doxorubicin intercalated the DNA, preventing the double helix from being resealed…stopping replication)
Side effects doxorubicin
Cardiotoxicity
Why does doxorubicin cause cardiotoxicity (leading to CHF)
Myocardial apoptosis, Dow Regulation of contractile proteins and oxidative stress on myocardial cells.
How can we decrease cardiotoxicity with doxorubicin
Give with dexrazoxane which is a cardioprotective agent
How does dexrazoxane work
Chelates iron ions, decreasing the amount of superoxide radicals that can harm the heart
Busulfan
Alkylation anticancer agent that is used to treat CML, and as a conditioning agent prior to bone marrow transplantation
MOA busulfan
Cross links DNA, preventing DNA replication, as these cross links cannot be repaired by cellular machinery, causing the cancer cell to undergo apoptosis
Indications for busulfan
CML
Bone marrow ablation (conditioning agent prior to bone marrow transplant, espicially in patients with CML)
What is the gold standard treatment for CML
Imatinib
Side effects busulfan
Myelosuppression Pulmonary fibrosis (busulfan lung) Hyperpigmentation (mimics Addison disease, affecting the joints and skin creases as bronzing)
Cyclophosphamide
Alkylation agent, which works by cross linking DNA at the guanine N7 position, causing cell apoptosis.
Before becoming active, cyclophosphamide is bioactivated by __ in the liver
Cp450
Indication for cyclophosphamide
Lymphomas (hodgkin and non Hodgkin))
Leukemia’s
Solid malignancies(breast, ovarian, cervical, testicular soft tissue sarcomas)
SLE, RA, MS, amyloid light chain amyloidosis
Side effects cyclophosphamide
Myelosuppression (decrease r and w bc, + thrombocytes)
Hemorrhagic cystitis(which can be treated with mesna)
SIADH
MOA cyclophosphamide
Pro drug—>4 hydroxy cyclophosphamide (chemotherapeutic activity from over conversion)
Alkylation agent that cross links DNA (adds to alkyl group at guanin N7 position) inhibiting replication
Indication for cyclophosphamide
Autoimmune disorders (depresses leukocyte replication)
Leukemias (kids too)
Lymphomas
Solid tumors
Side effects cyclophosphamide
Myelosuppression
Hemorrhagic cystitis
How does cyclophosphamide cause hemorrhagic cystitis
Produces acrolein
Which is toxic to the bladder epithelium
How treat hemorrhagic cystitis
Mensa
Adequate fluid intake
Risk with cyclophosphamide
TCC
How does Mensa work
Binds to acrolein
Vincristine (once in)
Antineoplastic medicationt hat prevents cell division
Indication for vincristine
Leukemia’s, lymphomas, solid tumors
Side effects vincristine
Peripheral neuropathy
Paralytic ileus
Unlike __, vincristine does not cause bone marrow suppression
Vinblastine (velban)
MOA vincristine
It is a vinca alkaloid that blocks mitosis during the metaphase of cell division. This action prevents the replication of cells and stops cellular growth
Inhibits microtubuels from moving chromosomes during metaphase of cell division. It binds to tubules, a component of microtubles to prevent synthesis and trigger apoptosis. Yb inhibiting microtubules, it causes cell death
Indications vincristine
Leukemia’s
Lymphomas
CHOP
Cyclophosphamide, hydroxydaunorubicin, and prednisone.
Vincristine and lymphomas
Used with other chemos and causes apoptosis of tumour cells and prevents spread of cancer
Side effects vincristine
Peripheral neuropathyparalytic( toxic to peripheral nerves. Disrupts neurotubules by binding to the protein tubules. Injures neurons by inhibiting the structures required for atonal transport of anzymes and organelles.
ileus (injure autonomic nerves and autonomic transmission between brain and the intestines)
Why are there minimal CNS side effects with vincristine
Does not enter the brain
Why is vincristine only given via IV
Not absorbed. Can cause severe skin irritation.
Cisplatin
Chemo which triggers apoptosis in tumor cells by crosslinking their DNA.
How is cisplatin administered
IV
Indications for cisplatin
Solid malignancies, carcinomas—-ovarian, pulmonary, bladder and testicular carcinomas.
Side effects cisplatin
Nephrotoxicity and ototoxicity
Indications for cisplatin
Carcinoma-bladder, ovarian, lung, testicular
MOA cisplatin
Interferes with mitosis, crosslinking DNA. Crosslinked DNA are unable to be replicated and are considered damage. The damage is irreperable, activation apoptosis
Side effects cisplatin
Ototoxicity-acoustic nerve damage…from reactive oxygen species that damage the stria vascularis of the inner ear.
Nephrotoxicity-creates ROS that damage kidney
Why should cisplatin never be combined with aminoglycosides
Otoxicity
How treat nephrotoxicity from cisplatin
Use amigos time, which scavenges free radicals and neutralizes them, along with chloride diuresis
Etoposide
Cytotoxic chemo used in treating malignancies like small cell lung cancer and testicular cancers
Off label indications for etoposide
Leukemia and lymphoma
MOA etoposide
Inhibits topoisomerase II, inhibiting proper DNA replication which leads to cancer cell apoptosis.
Side effects etoposide
Alopecia, myelosuppression, hypotension, nausea and vomiting
Indications etoposide
Small cell lung cancer
Testicular cancer
MOA etoposide
Inhibits topoisomerase II, which is crucial for DNA replication, working to cleave and unwind DNA supercoils and then to relegate them.
By inhibiting topoisomerase II, etoposide leads to errors in DNA synthesis, causing what
Apoptosis
Why do cancer cells rely on topoisomerase II more than health cells
They divide more
Side effects etoposide
Myelosuppression
Alopecia
Hypotension
Nausea and vomiting
Hydrozyurea
Antimetabolite medication which acts by suppressing ribonucleotide reductase, an enzyme that reduces ribonucleotides into deoxyribonucleoties which are necessary for DNA synthesis.
MOA hydroxyurea
DNA replication halted in the S phase of the cell cycle
Indication for hydroxyurea
Chronic myeloid our leukemia, melanoma, sickle cell disease
Side effects hydroxyurea
GI distress, myelosuppression
MOA hydroxyurea
Inhibits ribonucleotide reductase (which reduced ribonucleotides into deoxyribonucleotides, which are necessary for DNA synthesis)
Decrease DNA synthesis
Stuck in S phase-“activating the S phase checkpoint”
Indications hydrozyurea
Melanoma
CML
Sickle cel disease (effectively reverses suckling of cells, causes an increase of HbF and inhibits HbS)
Side effects hydroxyurea
Myelosuppression GI distress (acute mucocutaneous toxicity)
Bevacizumab
Monoclonal antibody cancer therapy that targets vascular endothelial growth factor (VEGF)
MOA bevacizumab
Monoclonal antibodies normally made by the body in that they attach to invasive cells. Targets VEGF, attaching to cancer cells that express VEGF signal protein, thereby signaling the immune system to kill these cancer cels.
What does the VEGF ligand normally bind to
It’s receptors on endothelial cells to help stimulate formation of new blood vessels either from endothelial cells (vasculogenesis) or from existing blood vessels (angiogenesis)
What does bevacizumab bind
VEGF extracellulary an preventing it from binding to VEGF receptors on the surface of endothelial cells
Effect of bevacizumab from binding to VEGF
Inhibiting VEGF from stimulating angiogenesis which inhibits tumor growth while antivascular effects reduce tomour size
Effect of bevacizumab on tumor
Anti-angiotensin effects inhibit tumour growth while antivascular effects reduce tumour size
Indications bevacizumab
Capillaries grow CORN (cc-CORN acronym) Colorectal cancer Glioblastoma Cervical cancer Ovarian cancer Renal cell carcinoma Non small cell lung cancer
Age related macular degeneration
Off label uses of bevacizumab
Metastatic HER2 neg breast cancer
Endometrial cancer
Retinopathy of prematurity
Diabetic retinopathy
Side effects bevacizumab
Impaired wound healing(inhibit growth of new bv, do not take before surgery-28 days before and after)
Hemorrhage (nosebleeds, cough vomit blood, vaginal, brain, spinal cord)
GI perforation(leak)
Thromboembolic event
Osteonecrosis of jaw(in conjunction with chemotherapy regimes)
Contraindications for bevacizumab
Recent he opts is or hemorrhage
Imatinib (gleevec)
Tyrosine kinase inhibiting med used for treating cancers, such as CML and GI stromal tumors.
MOA imatinib
Inhibits BCR-ABL tyrosine kinase enzyme (which is found in cancer cells), which is necessary for cancer growth. Also inhibits C-kit, which is involved in cell proliferation and differentiation in the GI stroma
Indications imatinib
CML (inhibitor of BCR-ABL tyrosine kinase)
GI stromal tumors (inhibitor fo C-kit tyrosine kinase)
Philadelphia chromosome
One of the most common forms of CML arises from the Philadelphia chromosome which is 9:22 translocation. A fusion gene is created as a result of this translocation, elongating chromosome 9 and pairing the ABI gene with the BCR gene from chromosome 22
What does C-kit do
Signaling role in cell survival, proliferation and differentiation leading to cancerous growth of the GI system
Side effects imatinib
Fluid retention
Edema
CHF
Also nausea headaches, pancytopenia and growth delay in kids
Rituximab
Monoclonal antibody medication targeting CD20
CCD20
A protein expressed on B cells.
Indications or rituximab
Disorders of B cell malignancy, dysfunction or excess
Side effects of rituximab
Infusion reactions at the site of IV administration, and the development of skin and oral reactions
Rituximab is associated with hte reactivation of what
Hepatitis B virus, along with the development of PML
Indications for rituximab
CLL Non Hodgkin lymphoma RA Microscopic polyangiitis (MPA) Wegeners (granulomatosis with polyangiitis)
Rituximab and CLL
Treats previously untreated and previously treated CD20 positive CLL and combined with fludarabine and cyclophosphamide
Rituximab and non hodgkin lymphoma
Destroys malignant and normal B cells with CD20
Rituximab and RA
Combined with methotrexate
MOA rituximab
Monoclonal antibody to CD20 (on B cells and causes conformational change making them visible to NK cells)
Side effects rituximab
Infusion reactions
Skin and mouth reactions
Reactivation of hep b
PML
PML
Rare , serious brain infection that can lead to severe disability and death. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body or blurred or lost vision
Tamoxifen
Selective estrogen receptor. Modulator which is a receptor antagonist in breast, but agonist in bone
Indication for tamoxifen
Estrogen receptor positive breast cancers
Beneficial side effect of tamoxifen
Decreased risk of osteoporosis is
Side effects tamoxifen
Increased risk of endometrial cancer and increased risk of thromboembolic event
MOA tamoxifen
SERM-antagonist for estrogen receptors in some tissues, while an agonist in others
Tamoxifen is antagonistic in _ tissue and agonistic in _
Breast
Bone
Indication for tamoxifen
ER positive breast cancer
Side effects tamoxifen
Decreased osteoporosis
Endometrial cancer
Increased risk of venous thromboembolism (VTE)
Trastuzumab/herceptin
Anticancer medicationt hat is a monoclonal antibody against HER2
HER2
Tyrosine kinase receptor that is overexpressed by breast cancer cells
Side efects treastuzumab
CHF and cardiotoxicity
Indications for trastuzumab
Her 2 positive breast cancer Stomach cancer(HER2 positive gastric cancers)
How many breast cancers are her2 positive
1/5
HER2+ gastric cancer
Overexpresses HER2 tyrosine kinase receptor, and is more responsive to trastuzumab
MOA trastuzumab
Monoclonal antibody against HER2 which binds to cancer class leading to antibody mediated killing HER2 positive cancer cells
Inhibits HER2 initiated cellular signaling.
Antibody mediated cytotoxicity
Side effects trastuzumab
Cardiotoxicity
Aroma rose inhibitors
Drugs used in women whoa re post menopausal with breast cancer
MOA aromoatse inhibitors
Block the production of estrogen or block the action of estrogen receptors
Indications aromatase inhibitors
ER+ breast tumors bc they require estrogen to grow.
Ovation tumors in postmenopausal women
Systemic metastasis of er positive breast tumors, which preferentially sprea to the liver, lungs, brain and bones.
Ovarian cancer and preventing gynecomastia in men
Examples of reversible, non steroid aromatase inhibitors
Letrozole
Anastrozole
Letrozole
For hormonal responsive breast cancer after surgery. Works via reversible inhibition
Anastrozole
For breast cancer after surgery, or metastasis in both pre and post menopausal women
Reversible inhibition
Irreversible, steroid aromatase inhibitors
Exemestane
Exemestane
Oral steroidal aromatase inhibitor that is used in ER positive breast cancer in addition to surgery and/or radiation in post menopausal women
Side effects aromatase inhibitors
Osteoporosis
Arthritis -estrogens have a positive effect on bone metabolism by stimulating bone growth and inhibiting bone resorption
Arthritis
