Anti-Neoplastics Flashcards
When is medical therapy needed for cancer?
Neoadjuvant therapy
Eradication of micro-metastasis
Medical treatment of sensitive tumour
Palliatation
When are chemotherapies most effective?
When tumours/metastasis are small
What considerations are there affecting medical therapies for cancer treatment?
Naturally resistant populations (tumour heterogeneity)
Tumour growth kinetics
Factors influencing drug penetration of tumour
Patient factors
How can cancer resistances be overcome?
Reduce tumour burden before medical therapy- surgery
Multi-drug chemotherapy
High dose intensity
Why is the frequency of treatment important?
If too far apart the tumour tissue has the time to regenerate
If too close together it is cumulative toxic to normal tissue
What factors affect response and side effects?
ADME A- Administration- dose/administration D- Distribution- target site M- Metabolism- activation, deactivation E- Excretion- clearance
What factors of response and side effects can be detected?
Pharmacogenetics- mutations in PgP
Co-morbidities
Poly-pharmacy
What are the two categories of chemotherapy and what are their mechanisms of action?
Damage DNA- cell cycle non-specific
Inhibits DNA replication- cell cycle specific
What is the problem with un-targeted therapy?
Well affect all rapidly dividing tissues
Where are the main side effects of un-targeted therapy?
Bone marrow- Low white count
Alopecia- uncommon in fods/cats
Gastrointestinal
What is the mechanism of action of the drug Alkylators?
Bind to DNA, insert on alkyl group leading to a change in structure- transcription and replication are inhibits
Cell cycle non-specific
What are the main mechanisms of actions of resistance of alkylators, where is is metabolised and excreted?
Resistance- DNA repair from MGMT/ Exclusion from cell
Metabolised to active by liver
Excreted by kidneys
What are the commonly used agents of alkylators and what are the side effects?
Chlormabucil, cyclophosphamide, lomustine, melphalan
Side effects- myelosupression, sterile haemoorhagic cystitis (cyclophospamide), Lomustine- hepatic toxicity
What is the mechanism of action of vinca-alkaloids?
Either binds to or inhibits formation of microtubules preventing the formation of mitotic spindle
Cell cycle specific
Where is vinca-alkaloids metabolised to active form and excreted?
Metabolised in liver
Excreted in the bile
What are the common used agents of vinca-alakloids and what are their possible side effects?
Vincristine, vinblastine, Vinorelbine GI Mylosupression Perivsascular irritation Mutations on PgP can lead to severe side effects TEST PATIENT
What is the mechanism of action of anti-tumour antibiotics and what are the main resistance mechanisms?
MOA-
Topoisimerase inhibtion- DNA strand breaks
Intercalation with DNA- prevents transcription
Free radical formation- DNA damage
Cycle non-specific
Resistance- upregulation of ABC-B1, topoisomerase II activity
Where are anti-tumour antibiotics metabolised and excreted?
Metabolised in liver
Excreted through bile
What drugs are used and what are the side effects of anti-tumour antibiotics?
Drugs- doxorubicin, epirubicin
Side effects- GI, Mylosupression, cumulative cardio toxicity, arrhythmia (admin too quickly), severe perivascular irritation
What is the mechanism of action of platinating agents and what are the mechanisms of resistance?
MOA- platinum binds both within and between strands
Resistance- decreased uptake, increased DNA repair, increases detoxifying enzymes
Where is platinizing agents metabolised and secreted?
Metabolised- isn’t
Excreted- kidney
What platiniating agents are used and what are the side effects?
Drug- carboplatin
Side effects- myelosuppression, GI toxicity, kidney toxicity
What is the mechanism of action, resistance mechanisms, normal metabolisation/excretion, drugs and side effects of anti-metabolites?
Interact with DNA production pathways, but differing mechanisms- cell cycle specific
Resistance- reduced uptake, reduction in pathway enzymes
Metabolised- liver, plasma
Excretion- kidneys
Drugs- cytosine arabinoside, fluorouracil
Side effects- mylosupression, GI, transient hepatic dysfunction
What is the mechanism of action of l’asparaginase, side effects, main use?
MOA- l’asparaginase metabolises asparagine to aspartic acid, malignant lymphocytes dependent on asparagine therefore lymphocyte death
Side effects- anaphylaxis (rare), pancreatic inflammation, transient alterations in liver function
Use- lymphoma, leukaemia
