Pharm cytotoxic Flashcards
Examples of Alkylating agents
1.Nitrogen mustards(3)
2. nitrosoureas (2)include
3.(1)
- Cross bridges : cyclophosphamide, mechlorethamine,
2. carmustine and lomustin
3. Busulfan
MAO Alkylating agents (2)
- can affect ALL phases of the cell cycle.
2 methods:
1. Disrupt the structure of DNA by adding an alkyl group to the guanine base= DNA fragmentation; when repairing base pairs & matched wrong = cell death
2. Forming of cross bridges prevents DNA separation = cell death
Indications for Alkylating agents
Nitrogen mustards
(cyclophosphamide, mechlorethamine, and ifosfamide)
leukemias, solid tumours (ovarian & Breast),
Indications of cyclophosphamide (5)
causes cross linking
1. Rx Ca- leukemias, solid tumours(ovarian& Breast)
- Rx vasculitis-GPA, microscopic polyangiitis &polyangiitis nodosa
- MS
4 severe RA
- Refractory cases of SLE
SE: All Alkylating agents
SIADH
Development of leukaemia
hair loss,
GI disturbances,
Infertility
teratogen
SE: cyclophosphamide
Haemorrhagic cystitis- to prevent Rx: Mensa
Myelosuppression,
Transitional cell carcinoma
Bladder ca
All Alkylating agents
SIADH
Development of leukaemia
hair loss,
GI disturbances,
Infertility
teratogen
Indications for Busulfan
(Alkylating agents) (2)
RX CML
Before bone marrow transplant as a part of myeloablative conditioning (kills all cells )
SE Busulfan (Alkylating agents)
suppression of the bone marrow
pulmonary fibrosis
hyperpigmentation
CNS toxicity
(Alkylating agents) Nitrosoureas
include:
rx
carmustine and lomustin
glioblastoma multiforme crosses BBB
Cytotoxics: Antimetabolites
- -Effect Phase
- -Mimic
-Effect S Phase
-Mimic Nucleobases or folic acid = Stop DNA
Cytotoxics: Antimetabolites 3 subclasses
- mimic purine: azathioprine and cladribine (rx harie cell leuk)
- mimic pyrimidine: cytarabine and 5-fluorouracil.
- Folic acid analogues -methotrexate
Indication azathioprine
CA 2
IBD 2
Autoimmune 3
Neuro 2
Inhibit purine syn
Ca: ALL & CML
IBD: UC (maintaining remission after severe replase),
Crohn’s –(add-on medication to induce remission)
Autoimmune:
Autoimmune hepatitis
SLE (3rd ln),
Polymyositis (2nd ln)
Neuro :Lambert-Eaton syndrome & Myasthenia gravis (to immunosuppress)
SE azathioprine
In pregnancy
-Bone marrow depression & Megaloblastic anemia
- Nausea/vomiting
- Pancreatitis
- Increased risk of non-melanoma skin cancer
considered safe to use in pregnancy
MAO Fluorouracil (5-FU)
Pyrimidine analogue- blocks thymidylate synthase (works during S phase)
SE Fluorouracil (5-FU)
Myelosuppression, mucositis,
dermatitis
photosensitivity
mucositis,
alopecia,
GI disturbances
CNS toxicity,
hand-foot syndrome.
Fluorouracil (5-FU) indications
Solid tumours:
- Colorectal
- pancreatic
- head & neck cancer,
- breast,
- ovarian
- bladder
- hepatocellular cancer.
- basal cell carinoma
Indications Methotrexate
leukemias, (ALL), lymphomas (NHL),
solid tumors: breast & bladder cancer
choriocarcinoma, (germ cell tumor)
unruptured ectopic pregnancy,
inflammatory conditions :RA, psoriasis, IBD, SLE , and dermatomyositis
SE Methotrexate:
Whic abx should not be used with
Myelosuppression, mucositis, liver fibrosis, lung fibrosis
The concurrent trimethoprim = bone marrow suppression and severe or fatal pancytopaenia
MOA of methotrexate
Inhibits dihydrofolate reductase and thymidylate synthesis
decrease in production of DNA, RNA & proteins
Name the 2 cytotoxic drug classes that act on microtubules- (Alkaloids)
- Drugs in the each category (2x2)
-How do their MAO’s differ
Vinca alkaloids
- block polymerization into protofilaments = unstable mitotic spindles (stop at metaphase)
Example vinblastine & vincristine
Taxanes alkaloids
- enhance tubulin polymerization into protofilaments and microtubules
= overstablizes the microtubules
Examples: paclitaxel and docetaxel
Indications for Taxanes alkaloids (overstablise mt)
solid tumors including breast, ovarian, lung, gastroesophageal, prostate, bladder, and head & neck cancers
Indications for Vinca alkaloids
Indications:
- breast ca;
- pediatric tumors (rhabdomyosarcoma, nephroblastoma, Wilms tumor)
- leukemias.
- both lymphoma.
cytotoxic SE: microtubules- (Alkaloids)
alopecia, GI upset myelosuppression; vincristine is more neurotoxic
Taxanes may cause a hypersensitivity rnx
Monoclonal antibodies
suffix “-umab” refers to
Only made of only human components
Least likely to induce hypersensitivity rnx
Monoclonal antibodies
suffix “-ximab” refers to
both human and non-human components
Monoclonal antibodies
suffix “-zumab” refers to
Humanized antibodies
MOA cetuximab
Uses (2)
-epidermal growth factor receptor antagonist EGFR
used in metastatic colorectal cancer
head and neck cancer
MAO trastuzumab/ herceptin.
Uses
HER2/neu receptor antagonist
used in metastatic breast cancer
gastric, ovarian, and lung ca
SE: Trastuzumab/ herceptin
cardiotoxicity
GI sx fever, chills, and headache.
MAO bevacizumab
Indications
which binds to VEGF, or vascular endothelial growth factors.
solid tumors in metastatic phase
Rx macular degeneration, w
SE: bevacizumab
inhibition of angiogenesis in normal tissues and leads to impaired wound healing.
Bleeding (hemorrhage )
MAO Rituximab
binds to CD20, an antigen found on B cell membranes = cell death through multiple mechanisms.
Indications Rituximab
non-Hodgkin B cell lymphomas
CLL
RA
SE Rituximab
hypersensitivity reactions
suppression of the immune system & reactivation of viruses such as JC virus= progressive multifocal leukoencephalopathy, or PML
MAO alemtuzumab
Indication
binds to CD52, which is found on the membrane of all lymphocytes including B cells, T cells, and natural killer cells, as well as monocytes and dendritic cells.
CLL
MAO Abciximab
& indication
-glycoprotein IIb/IIIa receptor antagonist):
- prevention of ischaemic events in patients undergoing PCI
MAO OKT3
Indication
(anti-CD3): used to prevent organ rejection
MAO Cytotoxic antibiotic Bleomycin
Oxidizes DNA bases = fragmented DNA
Effective in the G2 phase
Cytotoxic antibiotic Bleomycin
SE:
pneumonitis–> pulmonary fibrosis.
Skin toxicity (rash, exfoliation, & hyperpigmentation
stomatitis and mucositis in the mouth,
alopecia
only causes minimal myelosuppression, which is unusual for an anticancer medication.
Cytotoxic antibiotic Bleomycin indications
Hodgkin’s lymphoma
testicular cancer squamous cell carcinoma of the skin
Cytotoxic antibiotic: Anthracyclines ”RUBICIN”
Examples MAO (3)
doxorubicin, daunorubicin, idarubicin, and epirubicin.
1. intercalate w/ DNA inserting themselves between base pairs = inhibiting RNA and DNA synthesis
2. inhibit topoisomerase II = DNA will overwind during replication until it tears itself apart.
3. free oxygen radicals that damage the DNA strand,
mao Antitumor antibiotics
Examples
interferes with cell growth by disabling DNA replication, thus leading to cellular death
mitomycin, anthracyclines which include drugs like doxorubicin, actinomycin D, and bleomycin
Therapeutic drug monitoring post dose
Digoxin- at least 6 hrs post-dose
Lithium- take 12 hrs post-dose
Therapeutic drug monitoring pre dose
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose
Ciclosporin -trough levels immediately before dose
Vancomycin Monitor PRE-DOSE (trough) levels at 36 to 48 h
Gentamicin is re-started, re- check levels before the next dose
