Oncology Flashcards
Bleomycin MoA
induces free radical formation -> breaks DNA strands
Acts G2/M phase
Bleomycin used in?
testicular ca and hodgkins lymphoma
bleomycin ADRs
pulmonary fibrosis, skin hyperpigmentation, mucositis
Dactinomycin moa
intercalates into DNA -> prevents RNA synthesis
Uses of dacinomycin
wilms tumour, ewing sarcoma, rhabdomyosarcoma
Dactinomycin ADR
myelosuppression
Anthracyclines (doxorubicin and daunorubicin) MoA and use
generates free radicals
intercalates in DNA -> DNA breaks -> reduced DNA replication
inhibits topoisomerase 2
used in solid tumours, leukaemias, lymphoma
Anthracyclines (doxorubicin and daunorubicin) ADRs
dilated cardiomyopathy
myelosuppresion
alopecia
thiopurines MoA
purine analogs -> reduced de novo purine synthesis
AZA converted to 6-MP and activated by HGPRT
- inhibits PRPP-synthase and aminotransferase
thopurines ADRs
myelosuppression, GI/liver toxicity
6-MP inactivated by xanthine oxidase and TPMT (increased toxicity with allopurinol or feboxustat
Cladribine and pentostatin MoA
purine analogs -> unable to be processed by ADA -> reduced DNA synthesis and blocks DNA strand elongation
Cladribine and pentostatin use and ADR
in hairy cell leukaemia
ADR: myelosuppresion
Cytarabine MoA and use, ADR
pyrimidine analog -> DNA chain termination, inhibits DNA pol
used in AML, lymphoma
ADR: myelosuppresion
5-FU MoA
pyrimidine analog -> activated to 5-FdUMP which reduces DNA synthesis
capcitabine is a prodrug
what is used as 5-FU antidote
Uridine
What can enhance effects of 5-FU
folinic acid
ADRs of 5FU
myelosuppresion, hand-foot syndrome, photosensitivity
hydroxyurea MoA
inhibits ribonucleotide reductase -> reducing DNA synthesis
hydroxyurea ADRs
severe myelosuppresion, megaloblastic anameia
Methotrexate MoA
folic acid analog which inhibits dihydrofolate reductase -> reducing DNA synthesis
Methotrexate ADRs
myelosuppression
hepatotoxicity -> bx macrovesicular change
mucositis
pulmonary fibrosis
folate def
nephrotoxicity
busulfan MoA and use
cross links DNA -> cell death
used to ablate BM prior to transplant
busulfan ADRs
myelosuppression, pulmonary fibrosis, hyperpigmentation
cyclophosphamide, ifosfamide MoA
cross links DNA, needs activation in liver
cyclophosphamide, ifosfamide ADRs
myelosuppresion, SIADH, fanconi syndrome (ifosfamide - inadequate reabsorption in proximal tubules, reduced K and acidosis)
Haemorrhagic cystitis and bladder cancer (prevent with mesna)
carmustine, lomustine MoA and uses
cross link DNA, activates in liver
crosses BBB so used for brain tumours
carmustine, lomustine ADRs
CNS toxicity (dizziness, ataxia, seizures)
procarbazine MoA and ADRs
alkylating agent
ADR: myelosuppression, pulmonary fibrosis, leukaemia, disulfiram like reaction
platinum compounds MoA (cisplatin, carboplatin, oxaliplatin)
cross linsk DNA
cell cycle non-specific
platinum compounds ADRs
nephrotoxicity (fanconi)
peripheral neuropathy
ototoxicity
what prevents nephrotoxicity of platins
amifostine - detoxifies reactive metabolites
taxanes (docetaxel, paclitaxel) MoA
microtuble inhibitors
M-phase
hyperstabilises polymerised microtubles - prevents mitotic spindle breakdown
taxanes (docetaxel, paclitaxel) ADRs
myelosuppression
neuropathy
hypersensitivity
vinca alkaloids (vincristine, vinblastine) MoA
microtubule inhibitors
m-phase
bind beta-tubulin and inhibits it polymerisation into microtubles -> prevent mitotic spindle formation
vincristine ADRs
neuropathy (axonal), constipation
vinblastine ADRs
myelosuppression
topoisomerase inhibitors work in which cell cycle?
G2 and S phase
irinotecan, topotecan MoA and ADR
inibit topo 1
ADR - myelosuppression and diarrhoea
etoposide and teniposide MoA and ADR
inhibit topo 2
ADR: myelosuppression, alopecia
Tamoxifen MoA
selective estrogen receptor modulator
- antagonist at breast tissue
- partial agonist in endometrium and bone (reduces bone resorption)
blocks binding of estrogen to ER in ER positive cells
Tamoxifen MoA
hot flushes
increased DVT risk
endometrial cancer
Alemtuzumab target
CD52
Bevacizumab target
VEGF
Bevacizumab ADRs
haemorrhage, clots, impaired wound healing
Cetuximab target
EGFR
Trastuzumab target
HER2
Trastuzumab ADR
dilated cardiomyopathy (reversible)
pembrolizumab, nivolumab target
PD1
Atezolizumab target
PD-L1
Ipilimumab target
CTLA-4
Alectinib, crizotinib target
ALK
Erlotinib target
EGFR
imantinib, dasatinib target
BCR-ABL, plus other tyrosine kinases (c-kit in GIST)
Ruxolitinib target
JAK1/2
Bortezomib, ixazomib, carfilzomib target
proteasome (induces arrest at G2-M phase -> apoptosis)
Vemurafenib, dabrafenib target
BRAF
Palbociclib target
cyclin dependant kinases 4/6 (induces arrest at G1-S phase)
olaparib target
poly (ADP-ribose) polymerase -> reduces DNA repair
Aprepitant MoA
NK1 receptor antagonist
Ondansetron MoA
5-HT3 receptor antagonist
prochlorperazine/metochlopramide MoA
D2 receptor antagonist
Degree of mutation severity
frameshift > nonsense > missense»_space; silent
silent mutations
swap for same amino acid
missense mutations
swap for different amino acid
sickle cell
nonsense mutations
early stop codon
splice site mutations
retained intron (gaucher, marfans)
frameshift mutations
one deletion leading to all AA moving over (duchenne, MD, Tay-sachs)
Role of topoisomerase and drugs that inhibit
1 - breaks single stranded DNA
2 - double stranded
1 inhibited by irinotecan and topotecan
2 inhibited by etoposide and teniposide