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Pharm > Chemotherapy and immunosuppressive drugs > Flashcards

Chemotherapy and immunosuppressive drugs Flashcards

0
Q

Cyclophosphamide

A

Most potent nitrogen mustard

  • used for sarcoma, carcinoma, feline lymph proliferation disease, mammary carcinoma and lymphoma
  • prodrug (many active metabolites)
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1
Q

Nitrogen mustards

A

Alkylating agent
-alkylates various macromolecules(N7 of guanine base of DNA
-kill cancer cells and have toxic effect on rapidly diving cells
Ex cyclophosphamide

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2
Q

Chorlambucil

A

Nitrogen mustard, less potent and toxic than cyclophosamide. No biotransformation required. Immunosuppressive drug of choice for cats (ibd). Expensive.

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3
Q

Melphalan

A

Nitrogen mustard.

  • principle for treatment in plasma cell tumours ( multiple myeloma)
  • very toxic to bone marrow
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4
Q

Nitrosoureas

A

Only ones lipid soluble so will cross bbb

  • also alkylate DNA and are prodrugs
  • affect stem cells
  • used to treat Cns tumours, lymphosarcoma, and malignant melanoma
  • includes bcnu, ccnu, methyl-ccnu and streptozotocin
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5
Q

Cisplatin(platinol)

A

Cis-diamminedichloroplaninum
-binds to DNA bases with cross linking around platinum ion instead of alkyl group
Inhibit DNA synthesis (biggest effect in s phase)
Used for solid tumour like bronchiogenic carcinoma, osteosarcoma, and mast cell tumours)
Also used intralesionally for sarcoids and other skin tumours in horses
Very nephrotoxic!!

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6
Q

Carboplatin (paraplatin)

A

Second generation platinum derivative
Nitrosourea
-same efficacy as cisplatin but less nephrotoxic and ototoxic but do see thrombocytopenia.

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8
Q

Antimetabolites

A
  • Primarily active in the s phase of cell cycle.

- compete with normal substrates of cellular runs that are needed for proper cell fxn, regulation or division.

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9
Q

Methotrexate (MTX, Rheumatrex)

A
  • antimetabolite
  • binds and inhibits that DHF reductase enz (DHFR) which is necessary for DNA purine synthesis
  • interfers with RNA, DNA and protein synthesis
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10
Q

6-Mercaptopurine

A

-antimetabolite
-inhibits the enzymes involved in purine synthesis
(also used as immunosuppressive drugs)

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11
Q

5-Fluorouracil

A
  • antimetabolite
  • binds and inactivates the enzyme critical to the synthesis of thymine nucleotides (thymidylate synthetase)
  • topical or IV
  • dont use in cats
  • topically to tx squamous cell carcinoma in horses
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12
Q

Cytarabine (Cytosar, Ara-C)

A
  • antimetabolite
  • its active metabolite inhibits DNA polymerase thus blocks DNA synthesis
  • used to treat lymphoma and myelogenous leukemia (very suppressive to bone marrow)
  • works synergistically with L-asparaginase
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13
Q

L-asparaginase (Elspar, Kidrolase)

A
  • enzyme from E.coli
  • breaks down asparagine to aspartic acid
  • interferes with DNA, RNA and protein synthesis
  • specific for G1 phase of cell cycle
  • used in lymphoma, melanoma and mast cell tumours
  • not BM tumours
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14
Q

Vinca Alkaloids

A
  • derived from periwinkle plant
  • block polymerization of cellular microtubules and thus arrests mitosis in metaphase (M phase specific)
  • “spindle poisons” (tubulin affinity)
  • chemotherapy drugs
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15
Q

Vincristine (Oncovin)

A
  • vinca alkaloid (blocks polymerization of MTs –>arrest mitosis in M phase)
  • tx of lymphosarcoma, transmissible venereal tumours, mammalian neoplasia in cats and other solid tumours
  • dont use in dogs with ABCB-1 gene deletion (fatal)
  • also increases release of normal platelets from BM.
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16
Q

Vinblastine (Velban)

A
  • Vinca alkaloids (blocks MT polymerization and stops mitosis in M phase)
  • used for lymphosarcoma and disseminated mast cell neoplasia
17
Q

Doxorubicin (Adriamycin)

A
  • most common anti-tumour antibiotic in vet med
  • derived from Streptomyces peucetius
  • inactivates DNA by intercalating bw bases of the DNA molecule thus blocking synthesis of RNA and proteins
  • in addn binds cell membranes and alters ion transport and generates membrane cytotoxic free oxygen radicals
  • used in tx of lymphosarcoma, osteosarcoma and other carcinomas/sarcomas
  • nickname = Red Death
18
Q

ActinomycinD

A
  • antitumour antibiotic

- used for lymphomas and carcinomas

19
Q

Mitoxantrone (Novantrone)

A
  • antitumour antibiotic

- tx of lymphoma in cats and dogs

20
Q

Paclitaxel (Paccal Vet-CA1)

A
  • in the taxane class-cytotoxic agents that affect the MT network
  • promotes the assembly of Mts from tubulin dimers and stabilizes the Mts (preventing depolymerization) thus inhibiting reorganization of MT network needed for interphase and mitotic cellular fxns
  • used for nonresectable stage 3-5 mammary carcinoma and squamous cell carcinoma in dogs (with no prev chemo/radiation)
21
Q

Tyrosine kinase inhibitors

A
  • inhibit TKs which are responsible for activation of signal transduction cascades thro phosphorylation of various proteins
  • effective anti tumour and anti leukemic agents
  • often used in mast cell tumours
22
Q

Toceranib (Palladia)

A
  • TK inhibitor
  • tx of patnaik grade 2/3 recurrent cutaneous mast cell tumours +/- regional lymph node involvement
  • antitumour and antiangiogenic activit
  • specifically inhibits split kinase receptor TK family which are implicated in tumour growth, pathologic angiogensis and metastatic progression of cancer (leads to cell cycle arrest and apoptosis in tumour cell lines)
  • also inhibits TKs involved with VEGF receptor, platelet derived growth factor receptor and stem cell factor receptor.
  • antiproliferative effect on endothelial cells too
23
Q

Glucocorticoids (in chemo)

A
  • commonly used in combination protocols of chemo
  • prednisone, prednisolone usually
  • benefits include: Cytolysis of lymphoid cells, decreased inflammation, decreased SEs of other drugs,improved patient appetite and attitude and decreased cachexia from TNF
24
Q

Piroxicam (feldene)

A

-NSAID normally used for arthritis found to have anti tumour activity against transitional cell carcinoma of bladder and oral squamous cell carcinoma in dogs

25
Q

Glucocorticoids (immune mediated diseases)

A
  • tx of choice for most IMDs because of potent anti inflam and immunosuppressive effects
  • decrease Ab productions
  • action by changes to T cell pool distribution prob.
  • decrease lymphocyte numbers thus less activated T cells and less B cells for Ab production
  • reduce number of Ig receptors on macros
  • reduce phagocytic cell fxn by stabilizing lysosome membranes, reduce complement activation, inhibit chemotaxis and block PG and LK synthesis
  • must be administered aggressively
26
Q

Axothioprine (Imuran)

A
  • immunosuppressive drug
  • derivative of 6-MP (thiopurine) (metabolized to 6-MP in liver)
  • results in non fxnal nucleic acid strands
  • interfers with T cell fxn inhibiting cell mediated immunity and T cell dependent Ab synthesis
27
Q

Cyclosporine (Atopica)

A
  • immunosuppressive drug
  • used to treat IMHA and immune mediated dermatoses
  • blocks helper T cell production (no effect on suppressor T cells)
  • inhibits cytokine synthesis (IL2 and gamma-IFN)
28
Q

Leflunomide (Arava)

A
  • immunosuppressive drug
  • pyrimidine synthesis inhibitor
  • effective for immune mediated and inflame diseases of dogs that don’t respond to conventional tx
  • primary metabolite A77 1726 inhibits T and B cell proliferation (via inhibited pyrimidine biosynthesis and inhibited TK activity), supresses Ig production and interferes with cell adhesion
29
Q

Mycophenolate mofetil (CellCept)

A
  • immunosuppressive drug
  • prodrug of mycophenolic acid (MPA) which inhibits enz 5 monophosphate DH (needed for purine synthesis)
  • MPA inhibits T cell and B cell production, suppressing both cell mediated and humoral responses
  • both oral and parenteral forms
30
Q

Vincristine (Oncovin) (immune suppression)

A
  • immunosuppressive drug
  • vinca alkaloid that binds tubulin, disrupting platelet MT formation
  • macros phagocytose platelets with this, get cytotoxic dose and die?
  • also stimulates megakaryocytic division
  • IV dose used for emergency management of IM thrombocytopenia
31
Q

Human gamma globulin (Iveegam)

A
  • modulates immune response of IMHA and IMT
  • Ab blockade of Fc receptors on macros thus decreases removal of Ab coated RBCs from circulation
  • tx of dogs that fail to respond to conventional therapy only
32
Q

Antithrombotic Tx

A
  • Dogs with IMHA can get thromboembolism (fatal)

- low dose aspirin causes thromboprophylaxis improving survival rate

33
Q

Adjunctive therapies in IMHA and IMT

A
  • H2 blockers and sucralfate for GI irritation
  • splenectomy, tranfusions and plasmapharesis other tis.
  • survival need prompt recognition and aggressive therapy

Pharm (6 decks)

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