Oncology Flashcards
What detergent is most effective for dispersing oncology drug spills?
Bleach (hypochlorite)
What stages of the cell cycle do the following chemotherapy drugs work on:
a) Antimetabolites
b) Alkylating agents
c) Cross-linking agents
d) Toipomerase inhibitors
e) Antimicrotubule agents
f) Signal transduction inhibitors
a - d = S-phase (DNA replication)
e = mitosis (M-phase)
f = generally G1 (growth 1 phase)
MoA alkylating agents
Cross-linking of DNA leading to strand breaks by covalently binding alklyl groups to macromolecules within the cell
MoA anti-tumour antibiotics
Inhibition of toipoimerases and other mechanisms which interfere with DNA synthesis
Mitotic inhibitors MoA
Inhibit assembly of the mitotic spindle
Platinum compounds MoA
DNA cross linking
Anti-metabolites MoA
Incorporation into DNA interferes with DNA synthesis
Examples of the following oncologic drugs:
a) Alkylating agents
b) Anti-tumour antibiotics
c) Mitotic inhibitors
d) Platinum compounds
a) Cyclophosphamide, chlorambucil, melphalan, lomustine, procarbazine
b) Doxorubicin, mitoxantrone
c) Vinca-alkyloids
d) Cisplatin/carboplatin
Essentially if its not an anti-tumour antibiotic, mitotic inhibitor or platinum compound it is an alkylating agent
For Taxanes (Paclitaxel and Docetaxil) outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) anti-microtubule agents (M-phase specific)
b) Prevention of tubule organisation
c) Hypersensitivity reactions, myelosupression, diarrhoea
d) Hepatic metabolism - biliary excretion
e) Anti-histamines given prior to administration
For Vinca Alkaloids outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) anti-microtubule agents (M-phase specific)
b) Binding to tubulin prevents microtubule assembly
c) Tissue vesicants - HEAT and HYALURONIDASE (also topical DMSO and flucinolone and flunixin meglumine), peripheral myelopathies, alopecia, myelosupression, diarrhoea
d) hepatic metabolism and biliary excretion
e) Care with MDR1
For Cyclophasphamide outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent (nitrogen mustard)
b) Cross linking of DNA through insertion of an alklyl group
c) DLT include myeosupression (7 days), sterile haemorrhagic cytitis (prevented with frusemide), gastrointestinal signs and alopecia
d) Hepatic metabolism and renal excretion
e) Sterille haemorrhagic cystitis is a result of metabolism to acrolein which is directly toxic to the bladder mucosa. Specific treatments include pentosan sulfate, DMSO, oxybutinin and NSAIDs
For Chlorambucil outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent (nitrogen mustard)
b) Cros links DNA through insertion of an alkyl group
c) DLT - myelosupression which occurs after 2 - 3 weeks. Cerebellar toxicity, alopecia and GIT signs
d) hepatic metabolism and renal excretion
For Dacarbazine and Procarbazine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) Metabolised to MTIC which then methylates guanine
c) Cannot be used in cats as they don’t convert enough to the active form. DLT is GI side effects. Is also a vesicant.
For Ifosphamide outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent (itrogen mustard) - similar to cyclophosphamide.
b) Insertion of alklyl group
c) DLT = myelosupression, can also cause GI and bladder mucosal changes. It should be administered with mesna and fluids.
For Lomustine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) as for all alkylating agents
c) DLT is myelosupression which may occur after 7 - 10 days. Other side effects include hepatotoxicity and pulmonary fibrosis (cats).
d) Hepatic metabolism and renal excretion
e)
For Melphalan outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) as for all
c) Myelosupression, GI, pulmonary infiltrates and fibrosis have also been described.
d) 25 - 30% is excreted unchanged in the urine but it spontaneously degrades to inactive metabolites.
For Streptozoocin outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) It is selective for beta cells (and the kidney) as it requires uptake via GLUT2.
c) DLT is nephrotoxicity but can also cause hepatotoxicity
For Actinomycin D outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-tumour antibiotic
b) Complexes DNA and inhibits RNA synthesis
c) Myelosupression, GI signs and vesicant (use cold for treatment)
For Doxorubicin outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-tumour antibiotic
b) Complexes DNA, generates free radicals and inhibits toipoimerase activity.
c) DLTs = myelosupression (7 - 10d nadir) and GI toxicity (may result in colitis)
Cardiac toxicity can be acute (arrythmais) or chronic (DCM phenotype).
It is also a vesicant, the treatment is COLD, DMSO and dexraxozane
Nephrotoxic to cats
Dexraxoxone - how does it work?
Dexrazoxane is hydrolyzed to an active metabolite that chelates intracellular iron, which is believed to prevent the formation of an anthracycline-iron complex free radical that is thought to be the primary cause of anthracycline-induced cardiomyopathy and extravasation injury.
For Mitoxantron outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-tumour antibiotic
b) It is essentialyl the same as doxoruicin (synthetic analogue) so complexed DNA generates free radicals and inhibits toipoimerase.
c) It does not cause cardiotoxicity, can cause seizures in cats,
For Cytarabine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-metabolite
b) Inhibits DNA polymerase alpha and incorporation into DNA also results in apoptosis
c) Myelosupression and GIT signs
For Gemcitabine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
Anti-metabolite that inhibitis DNA polymerase. It has not been extensively used so little other information.
Methotrexate MoA
Inhibits dihydrofolate reductase and other folate metabolic pathways => inhibiting purine synthesis. It is not used much due to side effect profile.
For Rabacfosadine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-metabolite
b) Guanine nucleotide analogue
c) * GI
* Myelosuppression
* Hepatotoxicity
* Proteinuria
* Dermatologic toxicity
* Idiosyncratic pulmonary fibrosis (irreversible) - should not be used in patients with IPF
It is a vesicant which can be treated with cold and aspiration of the area
For 5-FU outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-metabolite
b) Uracil analogue
c) Myelotoxicity, GI toxicity, Neurotoxicity, Ingestion of topical cream can be fatal
For L-asparaginase outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) This is a miscellaneous drug.
b) Hydrolyses L-asparaginine to L-asparanagic acid. This is effective in cells that lack asparagine synthase (e.g. lymphocytes) which inhibits purine metabolism.
c) The main concern is that anaphylaxis can occur with repeat dosing. Rare side effects include pancreatitis, myelosupression and DIC
d) The body will quickly develop antibodies to L-asp so it becomes ineffective quickly.
For platinum compouds (cisplatin/carboplatin) outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Platinum based compounds
b) Covalent binding and cross-linking of DNA
c) Myelosupression, GI, renal (cisplatin only), pulmonary oedema and vasculitis (cats), hepatotoxicity, neuropathies and ototoxicity is also possible
For Hydroxyurea outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Misc
b) inhibits ribonucleoside reductase leading to a reduction in available RNA pools for protein synthesis
c) * GI, Myelosuppression, Pulmonary fibrosis, Methoglobinaemia (cats), Claw detachment (dogs)
What flow cytometry markers identify T-cells generally and more specifically?
CD3 & 5 identify T-cells generally
CD4+ and CD8+ identify specific subtypes
What flow cytometry markers identify B-cells?
CD21
Also:
- CD22
- CD79a
- Pax5
Which flow cytometry markers identify lymphoid cells?
CD45, CD11a
What flow cytometry marker differentiates immature (blasts) from matture lymphoid populations?
CD34
What cell types does MHC expression identify?
Monocytes, B-lymphocytes and T-cells
Which cell markers identify monocytes AND neutrophils?
CD18
Which cell marker identifies monocytes
CD14