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pharmacology sem 2 > cancer > Flashcards

cancer Flashcards

1
Q

what is temozolomide broken down into?

A

diazomethane, a highly reactive cation

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2
Q

what are the actions of diazomethane?

A

it reacts with neucleophilic centres on proteins and neucleic acids to methylate guanine and adenosine

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3
Q

what does methylating residues on DNA do?

A

it forms DNA lesions and leads to apoptosis

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4
Q

what type of glioma is IDH promoter methylated?

A

olgiodengliodendroma and astrocytomas

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5
Q

what is the mutation that leads to IDH1 and 2 mutations?

A

1p19q co-del

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6
Q

what are the potential genetic and histological changes which occur in glioblastomas?

A

EDGR gene amplification
TERT promoter amplification
microvascular proliferation
necrosis
PTEN promoter mutations
copy no. changes in chromosomes 1,7,9,10 and 19

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7
Q

what are the histological features associated with glioblastomas?

A

microvascualr proliferation
necrosis WITH PSEUDOPALSING
increases mitoses
significant heterogenicity

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8
Q

how does vinchristine work?

A

its inhibtis actin polymerisation by binding to beta-tubulin which is needed for microtubule polymerisation
inhibiting mitosis in the M phase, stopping the cell cycle, where the cell undergoes apoptosis or depolymerates to stop cell division

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9
Q

how does carmustine work?

A

its an anti-neoplastic alkylating agent which acts by alkylating NEUCLEOPHILIC CENTERS on proteins and gunanine at the O-6 position to form cross-linkages

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10
Q

what actions does procarbazine have after metabolic activation?

A

it inhibits trans-methylation of methoionine into tRNA to prevent DNA and RNA synthesis and as a result, protein synthesis

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11
Q

what are the actions of lomustine?

A

its an alkylating agents which reacts with neucelophilic centers on proteins and neucleic acids to inhibit DNA replication
forms cross links either DNA-DNA or DNA-protein

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12
Q

what are the side effects of vincristine?
+ treatments

A

autonomic neurophathy
pain in abdomen and jaw
hair loss, loss of appetite and confusion
treated with ibuprofen or duloxetine or gabapentin

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13
Q

what is the stupp protocol?

A

surgery> concominant radiation and chemotherapy (temozolomide for gliobastomas or PCV for the rest)

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14
Q

what is PCV treatment?

A

treatment for brain cancers (not glioblastomas) with vincristine, promazapine and lomustine

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15
Q

what dye do you use to resect brain tumors?

A

5-ALA which is metabolised into protoprophyine IX which is cleared by normal tissued and accumulates in tumors due to ferrochelatase deficiency

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16
Q

what is the neural diathesis-stress model of SZ?

A

proposes that stress, through its effects on cortisol production, acts upon a preexisting vulnerability to trigger and/or worsen the symptoms of schizophrenia.

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17
Q

What is glioblastoma?

A

A type of aggressive brain tumor originating from glial cells.

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18
Q

True or False: Glioblastomas are the most common primary brain tumors in adults.

A

True

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19
Q

What is the standard first-line treatment for glioblastoma?

A

Surgical resection followed by radiation therapy and chemotherapy.

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20
Q

Fill in the blank: The chemotherapy drug commonly used for glioblastoma is ______.

A

temozolomide

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21
Q

What role does radiation therapy play in the treatment of glioblastomas?

A

It helps to kill remaining tumor cells after surgery.

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22
Q

Multiple Choice: Which of the following is NOT a treatment option for glioblastomas? A) Surgery B) Chemotherapy C) Homeopathy D) Radiation

A

C) Homeopathy

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23
Q

What is the purpose of the Stupp protocol in glioblastoma treatment?

A

To establish a standard treatment regimen combining surgery, radiation, and chemotherapy.

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24
Q

True or False: Glioblastomas are considered curable with current treatments.

A

False

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25
What is the median survival rate for patients with glioblastoma after standard treatment?
Approximately 15 months.
26
Fill in the blank: Glioblastomas are classified as ______ tumors according to the WHO grading system.
grade IV
27
What is the significance of MGMT promoter methylation status in glioblastoma treatment?
It predicts the response to temozolomide chemotherapy.
28
Multiple Choice: Which of the following is a common side effect of radiation therapy for glioblastoma? A) Hair growth B) Nausea C) Increased appetite D) Improved cognitive function
B) Nausea
29
What is the role of clinical trials in the treatment of glioblastomas?
To test new therapies and improve treatment outcomes.
30
True or False: Immunotherapy is currently a standard treatment for glioblastomas.
False
31
What is the function of tumor-treating fields (TTFields) in glioblastoma management?
To disrupt cancer cell division using electric fields.
32
Fill in the blank: The use of ______ therapy is being investigated as a potential treatment for glioblastoma.
immunotherapy
33
Multiple Choice: Which imaging technique is commonly used to monitor glioblastoma treatment response? A) X-ray B) MRI C) Ultrasound D) CT scan
B) MRI
34
What is a common challenge in treating glioblastomas?
Their tendency to recur and infiltrate surrounding brain tissue.
35
True or False: Glioblastomas can often be completely removed through surgery.
False
36
What is the importance of multidisciplinary care in glioblastoma treatment?
To provide comprehensive management involving neurosurgeons, oncologists, and supportive care teams.
37
Fill in the blank: Patients with glioblastoma often experience ______ cognitive deficits.
progressive
38
What is a key factor influencing the prognosis of glioblastoma patients?
Age at diagnosis and performance status.
39
Multiple Choice: Which of the following is a potential future direction for glioblastoma treatment? A) Genetic therapy B) Herbal remedies C) Homeopathy D) Traditional chemotherapy
A) Genetic therapy
40
What is the role of supportive care in glioblastoma treatment?
To manage symptoms and improve quality of life.
41
True or False: Glioblastoma treatment is solely focused on extending survival.
False
42
what is the problem with the MGMT promoter being methylated?
it means theres MGMT protein expression and the effects of the alkylating agents (alkylating mismatch) will be reversed leading to tumors resistant to TMZ and worse survival
43
what does MGMT stand for?
suicide enzyme methylguanine-DNA methyltransferase
44
why is MMR crutial to TMZ cytotoxicity?
DNA mismatch repair is crutial for TMZ cytotoxicity therefore downregulaing MMR or upregulating MGMT production leads to TMZ ineffectiveness
45
what is the role of VEGF in glioblastomas?
it makes the tumor highly vascularised due to hypoxic regions and is a potent angiogenic factor leadind to vascular endothelial proliferation
46
what drug targets VEGF?
bevacizumab is a neutralising VEGF Ab which inhibits angiogenesis and vascularisarion, has been shown to prolong pregression free survival but not overall survial
47
what countries is bevacinumab indicated for the treatment of glioblastomas?
japan, US and canada
48
what effect does mutant IDH1 have?
it breaks alpha-ketoglutarate down to 2-HG which acts as an antagonist of α-KG to competitively inhibit the activity of α-KG-dependent dioxygenases which play many roles in tumorogenesis
49
why can preexisting EGFR antagonists not be used for the treatment of glioblastomas?
as the mutation is in the extracellular domain rather than the kinase domain like in small cell lung cancers and theyve got little BBB permeability
50
what is regorafinib?
its a multi-target tyrosine kinase inhibitor targeting angiogenesis genes- VEGFR-1-3 and TIE2 oncogenesis genes- KIT, RAF1, RET and BRAF TME- PDGFR, FGFR and CSF-1
51
what are the risk factors for brain tumors?
chemical exposure, radiation exposure and rare inherited diseases i.e. digeorge, lynch syndrome (mutations in MMR genes), p53 mutations (involved in DNA repair
52
what are the cardiovascular side effects from alkylating agants?
increased oxidative stress leads to emdothelial capilary damage which leads to cardiomyocyte death and heart failure arachidonic pathway leads to increased platelet reactivity and risk of thrombolytic events which can cause MIs
53
what chemo drug cause nephrotoxicity?
alkylating agents such as chlorpromazine, temozolomide and lomustine
54
why are alkylating agents associated with high mobidity and mortality?
becuase of their cv toxicity
55
why is the use of VEGF inhibitors limited?
becuase of their hypertenisve effects due to their effects on PLA2 > PGs and PI3K leading to the production of NO up to 80%
56
what are the epigenetic changes that occur in glioblastomas?
epigenetic changes are changes in DNA expression and commonly occur in CpG islands where promoters become hypermethylated leading to changes in genes associated with angiogenesis, supression of DNA repair, inhibition of apoptosis, cell cycle regulation and tumor supression
57
what are the side effects of TKIs? | give reasons for the side effects
the inhhibition of the PI3K and PGI2 pathways leads to inhbition of vascular tone and vasodilation leading to 40-60% of patients becoming hypertensive on these also renal toxicity and decreased lymophgenesis leading to salt sensitivity and protein urea microvascular rarefaction leads to decreased angiogenesis and a greater risk of heart failure all the side effects lead to an increased risk of CVD, MI and heart failure
58
how do you treat the side effects of TKIs?
with antihypertensives, if >160/90, then give ACEi or ARB like losartan or ramipril + a CCB like amlodipine if <160/90, then only give an ARB or ACEi
59
what are the side effects of alkylating agents?
they affect the NFkB (cardiac remodelling), NOS (endothelial injury and inc extravasation) and AA (inc plateley activity and thrombolytic effects=MI) (AA+ NOS ^ MI risk) pathways leading to cardiotoxic side effects ending in heart failure 32% of patients have CV side effects
60
what are the side effects of immune checkpoint inhibitiors?
60-80% of patients have immune related adverse events with myocarditis being the most common but also vascular injury, arrhythmias, pricardial disease, myocardial damage and
61
what are the side effects of cisplatin, a platinum based chemo?
its taken up in the renal tubule and activated when hydrated leading to primary nephrotoxicity side effects, then secondary side effects are cardiovascualr side effects which is linked with the risks seen in environmental heavy metal contaminants, the inc risk of CVD contributes massively to the morbidity and mortality seen in those treated with platinim-based chemos
62
what are the treatments to the side effects seen due to immune checkpoint inhibitors?
treating the underlying issues of immune activation with prednisolone for mild symptoms and methylprednisolone for severe if still unaffected, consider immunosupressants like mycophenolate mofetil or aziothioprine
63

pharmacology sem 2 (5 decks)

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