Oncology Flashcards
Mechanism of action of anthracycline (e.g., doxorubicin)
Stabilises DNA topoisomerase II complex inhibits DNA and RNA synthesis
Side effects of Methotrexate
Myelosupression
Mucositis
Liver Fibrosis
Lung Fibrosis
Mechnism of action of 5-Fluorouracil
Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (S phase)
Adverse effects of 5-fluorouracil
Myelosupression
Mucositis
Dermatitis
Function of mercaptopurine
Purine analogue activated by HGPRTase decreasing purine synthesis
Side effect of Mercaptopurine
Myelosupression
Mechanism of action of Cytarabine
Pyrimidine antagonist - inhibits DNA Polymerase
Side effect of Sytarabine
Myelosupression
Mechanism of action of Vincristine
Inhibits formation of microtubules
Side effect of vincristine
Peripheral neuropathy
Mechanism of atcion of docetaxel
Prevents microtubule depolymerisation
Side effect of docetaxel
Neutropenia
Name a topoisomerase inhibitor
Iriniotecan
Side effects of Irinotecan
Myelosupression
Mechanism of action of cisplatin
Cross linking in DNA
Side effects of Cisplatin
Nephrotoxicity
Ototoxicity
Peripheral Neuropathy
Hypomagenesaemia
Mechanism of action of hydroxyurea
Inhibits ribonucleotide reductase
What is Prophase
Centrosomes duplicate forming microtubules
What is Metaphase
Chromosomes align in the middle of the cells.
The microtubules attach to the centromeres on either side
What is anaphase
The chromosomes are separates and moved by centromeres to the other side
What is Telophase
The membrane separates to form two cells
Name the three check points in cells
G1
G2
M-phase
What happens in the S phase
DNA replication - during this Helicase separates the two dna strands
This causes super coils as the process continues.
Topoisomerase II fixes supercoils to reduce tension on the DNA (ie., stop damage).
Role of alkylating agents
Bind to nucleotides, form cross links with DNA strands which stops normal replication or cell division - causes cell arrest
Causes apoptosis.
Examples of alkylating agents
Cyclophosphamide and Cisplatin
How do anthracyclines function
Inhibits Topoisomerase II causing DNA to not relax -> causes it to break!
What is the DVT Well’s score criteria and associated score meanings
Active Cancer
Paralysis
Bedridden for 3 days or surgery within 12 weeks
Localised tenderness
Entire leg swollen
Calf 3cm nbigger than the other
Pitting Oedema
COllateral superficial veins
Orevious DVT
An alternative diagnosis has been excluded.
DVT likely if over 2
Management of Wells’ score over 2
Proximal leg vein ultrasound within 4 hours.
Positive then anticoagulate
Negative then do d-dimer.
If both negative consider another diagnosis
If Ultrasound is negative but d-dimer is positive, what should be done
Stop therapeutic anticoagulation
Offer repeat leg vein ultrasound 6-8 days later
If a DVT is unlikely in Well’s score, what should be done
Perform d-dimer test
Management of a VTE
DOAC first line then LMWH followed by a DOAC or LMWH followed by Vit K antagonist (ie., warfarin)
What is responsible for the break down of fibrin clots
Plasmin
How does tissue factor result in DIC
Upon extensive trauma, TF is exposed on teh surface of many cells, this binds to coagulation factors activating the extrinsic pathway and intrinsic pathway
Blood tests for DIC
Low platelets
Low fibrinogen
Increased PT AND ApTT
Schistocytes due to microangiopathic hameolytic anaemia
What drugs can induce pancytopaenia
Cytotoxics
Antibiotics (trimethoprim and chloramphenicol)
Gold and Penicillamine
Carbimazole
Carbamazapine
Tolbutamide
What is an ECOG score
Performance status of a patient measure
Causes of Eosinophilia
Pulmonary:
Asthma
Aspergillosis
Churg-Strauss syndrome
Loffler’s
Eosinophilic penumonias
Hypereosinophilic syndrome
Infective:
Schistosomiasis
Nematoses (TOxocara, Ascaris, Strongyloids)
Echinococcus
Drugs: Sulfsalazine and nitrofurantoin
Psoriasis/Eczema
Role of Thrombin (Factor 2)
Increases platelet activation
Factors 8, 11, 5, 13
Describe the process in which Factor 5 usually gets inactivated
AT the end of the formation of a mesh, thrombin binds to thrombomodulin recpetors on the endothelial cells
Protein C then joints the party with Protein S.
When protein S binds to Protein C, this leaves a gap in Protein C’s back.
Factor 5 gets caught off guard by this gap and gets cleaved - stopping further fibrin mesh production
What is the result of cleaving Factor 5
Stops Factor 10 and 9 activation
What type of mutation causes Factor V leiden deficiency
Singel point mutation where an amino acid is replaced by another
How is Factoe V Leiden deficiency inherited
Autosomal Dominant
WHat type of Factor V Leiden deficiency carry the highest risk of VTEs
Factor V Leiden (Heterozygeous)
Role of Glutathione
Anti-oxidant - neutralises free radicals
Usually are reduced. Can donate H+ to free radicals to produce water instead.
It then gets oxidised in the process.
Glutathione reductase donates a H+ back to Glutathione to reduce it again so it can function.
In the process Glutathiona Reductase recieves another H+ from NADPH
NADP+ as a bbyproduct.
Role of G6PD
Reduces NADP+ to NADPH from glucose-6-phosphate
How is G6PD deficiency inherited
X-Linked recessive
Only affects men (not dominant)
What happens in G6PD Deficiency
Enzymes do not last very long.
What does G6PD deficiency provide protetcion against and why
Protects against Falciparum Malaria due to reduced half-life of G6PD. Means that erythrocytes are more likey to die from free radicals that are not being swept up by glutathione.
Why do we get bite cells in G6PD deficiency
RBCs haemo get destroyed by free radicals, leaving heinz bodies.
Splenn macrophages detect they are abnormal and take a bit of the red cells leaving bite cells
What happens to Glutathione and NADPH in G6PD deficiency
Decreased all of them
Causes for G6PD Deficiency causes
Food:
Fava Beans
Soy
Red Wine
Infections:
Viral Hepatitis
Pneumonia
Medications:
Primaquine and Chloroquine
NSAIDs + Aspirin
Quinidine
Trimethoprim + Sulphonamides
What drugs can cause G6PD Haemolysis
Primaquine
Ciprofloxacin
Sulphonamides, Slufonylueras, Sulphsalazine
What ethnicity are affected by G6PD Deficiency
African and Mediterranean
What is G6PD Deficiency diagnosed
Measure enzyme activity of G6PD
How is Li-Fraumeni syndrome inherited
Autosomal Dominant
On what chromosome is BRCA1 carried on
17
On What chromosome is BRCA 2 carried on
13
What gene mutation is associated with prostate cancer in men
BRCA2
What is the Amsterdam criteria
Three or more family members with a confirmed diagnosis of colorectal cancer (first degree)
Two sucessive affected generations
One or more colon cancers diagnosed under 50
What drug can be given to increase neurophil count in neutropenic patients and how do these work
Filgrastim - granulocyte-colony stimulating factors
What translocation causes mantle cell lymphoma
11:14
What does 11:14 translocation do to cause mantle cell lymphoma
Deregulation of cyclin D1 gene
What happens in 14:18 translocation to cause follicular lymphoma
Increased BCL-2 transcription
What two malignancies are caused by EBV
Hodgkin’s and Burkitt’s lymphoma
What malignancy is caused by HTLV-1 infection
T cell leukaemia/lymphoma
What haematological malignancy can be caused by HIV
High grade B Cell lymphoma
What infection typically results in Burkitt’s lymphoma
Malaria
Causes of extravascular haemolysis
Sickle cell, thalasaaemia
Hereditary Spherocytosis
Haemolytic disease of the newborn
Warm autoimmune haemolytic anaemia
Symptoms of hairy cell leukaemia
Pancytopaenia
Splenomegaly
Vasculitis (skin)
DRY TAP on bone marrow
TRAP positive
Management of Hairy cell leukaemia
Chemotherapy - Cladribine and pentostatin
How is hereditary angioedema inherited
Autosomal Dominant
Blood test reuslts in hereditary angiooedema
C1-INH levels low during attacks
Low C2 and C4 between attacks
Symptoms of hereditary angiooedema
Painful macular rash
Painless swelling of tissues
NO URTICARIA
Management of Hereditary Angiooedema
IV C1-inhibitor concentrate
NB: Does not response to antihistamines or adrenaline
Prophylaxis of hereditary angiooedema
Danazol
Most common type of Hodgkin’s lymphoma
Nodular sclerosing (good prognosis)
What type of Hodgkin’s lymphoma has the worst prognosis
Lymphocyte depleted
the presence of b-symptoms
What Hodgkin’s lymphoma carries the best prognosis
Lymphocyte predominant
