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Case of unfair diagnosis Flashcards

1
Q

activation of transmembrane tyrosine kinase receptors?

A

growth factor binds to receptor causing dimerisation and autophosphorylation causing downstream activation of signalling cascade

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2
Q

mutations causing dysregulation of tyrosine kinase receptor?

A

ligand independent firing, autocrine growth factors

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3
Q

which tyrosine kinase growth factors are altered in human tumours?

A

erb b2, her2, neu, egfr

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4
Q

common mechanism of resistance to TKIs?

A

T790 mutation

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5
Q

first line for tyrosine kinase mutations?

A

osimertinib

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6
Q

lung cancers can often present with?

A

recurrent chest infections
pleural effusion

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7
Q

how to geta biopsy for lung cancer?

A

EBUS and tbna

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8
Q

appearance of adenocarcinoma?

A

located peripherally columnar glandular cells

BerEP4+, MOC31+, TTF-1 markers
associated with. EGFR, ALK, PDL1 ROS1 changes

lymphovascular invasion- which is why they have hilar lymph nodes involved

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9
Q

squamous cell carcinoma signs?

A

centrally, bronchial trees, squamous cell keratinisation, desmosomes
p40+. p63+, CK5/6+

PDL1 mutation

cavitate and sometime haemorrhage

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10
Q

small cell (neuroendocrine cells)

A

very blue cells, small cells, smudged nuclei

CD56, chromogranin positive
TTF1 nuclear - usually present in lungs

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11
Q

mesothelioma?

A

WT-1, calretinin positive
TTF-1, MOC31, napsin, p40 negative
aggressive, encasement of lung

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12
Q

Metastasis to the lungs?

A

colon- CK20, CDX-2, SATB2 positive
Breast- ER/PR, GATA3 positive
Prostate- PSA positive
Melanoma- s-100, melan A, SOX-10

usually bilateral multiple, appearance like origin, sharply outlined, rapidly growing and necrotic
lymphangitic carcinomatosis

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13
Q

pseudogenes?

A

shares a large amount of DNA with another gene

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14
Q

14 hallmarks of cancer?

A

sustain proliferative signalling
deregulating cellular metabolism
resisting cell death
genome instability and mutation
inducing or accessing vasculature
activating invasion and metastasis
tumour promoting inflammation
enabling replicative immortality
avoiding immune destruction
evading growth suppressors
senescent cells
polymorphic microbiomes
nonmutational epigenetic reprogramming
unlocking phenotypic plasticity

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15
Q

MEN2 is caused by which gene mutation?

A

RET
medullary thyroid cancer -90%
phaechromocytoma-50
parathyroid adenoma- 20-30%
familial medullary thyroid cancer- 100% risk

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16
Q

MEN2B?

A

same risk for medullary thyroid/phaechromocytoma
but other abnormalities 40-40
mucosal neuromas
marfanoid
toxic megacolon
>95%= always de novo

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17
Q

most frequent somatic mutation?

A

LOF- TP53 85% of tumours

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17
Q

most frequent somatic mutation?

A

LOF- TP53 85% of tumours somatic

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18
Q

BRCA1 is?

A

more common as germline

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19
Q

BRCA1?

A

BREAST CANCER ER NEGATIVE 80% OF THE TIME

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20
Q

Li Fraumeni syndrome?

A

inherited alteration in TP53

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21
Q

role of TP53?

A

DMA damage repair
induction of apoptosis
cellular metabolism
transcription
induction of G1 arrest

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22
Q

treatment for angiogenesis?

A

inhibitors of VEGF signalling

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23
Q

treatment for invasion/metastasis?

A

inhibitors of HGF/c-met

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24
treatment for promoting inflammtion?
selective anti-inflammatory drugs
25
target for replicative immortality?
telomerase inhibitors
26
target for avoiding immune destruction
immune activating anti-CTLA4 mAB
27
target for evading growth suppressors?
cyclin-dependent kinase inhibitors
28
target for proliferative signaling?
EGFR inhibitors
29
target for deregulating cellular epigenetics?
aerobic glycolysis inhibitors
30
target for resisting cell death?
proapototic BH3 mimetics
31
target for genome instability?
PARP inhibitors
32
SSRI discontinuation syndrome?
agitation, anxiety, dizziness balance problems, nausea diarrhoea, flu like symptoms commonest with paroxetine- either reassure/ monitor, reintroduce drug and taper or consider alternative
33
dotheipin requires?
more ecg monitoring as it is cardiotoxic
34
anticholinergic effects
constipation urinary retention cognitive effects dry mouth
35
akathisia can be treated with?
propanolol
36
EXAMPLES OF SSRIS?
fluoxetine, paroxetine, setraline, citalopram, escitalopram
37
indications for SSRIs?
depression, anxiety disorders, panic disorder, obsessive compulsive disorder, PTSD
38
half life of ssris?
paroxetine-20 hours fluoxetine-2/4days
39
fluoxetine side effect
agitation
40
mirtazapine is?
noradrenergic and specific serotonergic antidepressant alpha 2 receptor antagonist helps with insomnia make neurons activated
41
downside of mirtazapine?
more hungry
42
mirtazapine helps by?
antidepressant, anxiolytic, sleep restoring, no sexual dysfunction no gi problems
43
adverse effects of tricyclics?
dry mouth, constipation, urinary retention, cognitive effects, psychotropic effects agitation and nightmares, sexual dysfunction, akathisia, muscle twitches, cardiac arrhythmias
44
overdose of tricyclics?
confusion, tachycardia/arrhythmias, hypotension, mydriasis seizures, coma and cardiorespiratory arrest
45
what is particularly effective for mixed depression and anxiety?
venlafaxine
46
side effects on SNRI venlafaxine?
headache, nausea, hypertension, discontinuation syndrome duloxetine - no concerns of hypertension
47
MAOIs interaction?
food-cheese, red wine, yeast production liver, broad bean pods, tyramine, which is not broken down by MAO. causes hypertensive crisis moclebamide lower risk Seretonin syndrome- autonomic hyperactivity (hypertension tachycardia), muscle rigidity, fever, confused.
48
how does NASSA work mirtazaoine?
release of seretonin and noradrenaline via alpha 2 receptors on presynaptic neurone
49
SNRI examples?
venlafaxine, duloxetine
50
MAOI examples?
moclebamide, phenelzine
51
What does dopamine control?
executive function, lactation, motivation, motor control, reward, nausea
52
dopamine pathways?
mesocortical- prefrontal cortex motivation negative symptoms mesolimbic-nucleus accumbens positive symptoms nigrostriatal- caudate nucleus/putamen parkinsonian symptoms tuberoinfundibular-pituitary gland- hyperprolactinaemia
53
typical antipsychotics are?
d2 receptor antagonist so help with positive symptoms
54
typical antipsychotic side effects?
too little dopamine in tuberofundibular- hyperprolactinaemia amenorrhoea, sexual function, galactorrhoea and osteoporosis nigrostriatal- extrapyramidal effects
55
seretonin hypothesis?
hallucinogenic drugs LSD structurally similar to serotonin
56
glutamate hypothesis?
Phencyclidine- glutamate agonist which produces schizophrenia like symptoms, abnormal glutamate activity in schizophrenia
57
typical antipsychotics neurological side effects?
extrapyramidal symptoms- parkinsonism, akathisia, dystonia tardive dyskinesia
58
typical antipsychotic examples?
haloperidol, chlorpromazine
59
atypical antipsychotics details?
not specific for d2 receptors, can act on seretonin risperidone, olanzapine, quetiapine, aripiprazole
60
what are the problems with atypicals?
weight gain and metabolic syndrome particularly olanzapine
61
muscarinic side effects?
dry mouth, constipation, urinary retenion, blurred vision, dry eyes, tachycardia, dyspepsia, dizziness, impaired cognition/memory
62
side effects of adrenergic antagonist alpha blockers?
orthostatic hypotension, palpitation, sexual dysfunction and vertigo
63
why is clozapine reserved for treatment resistant cases?
haematological side effects low EPS, but can cause hypotension, hypersalivation and weight gain and can cause constipation
63
why is clozapine reserved for treatment resistant cases?
haematological side effects low EPS, but can cause hypotension, hypersalivation and weight gain and can cause constipation
64
Clozapine binds with high affinity to?
M1, 5HT21, H1, a1 and a2
65
rapid tranquilisation when patient aggressive?
antipsychotics- haloperidol, olanzapine benzos- lorazepam or midazolam
66
mood stabiliser?
lithium valproate lamotrigine carbamazepine
67
lithium method of action?
second messenger- inhibition of inositol, regulation of gene expression, protein kinase c
68
lithium side effects?
polydipsia, polyuria nauseau fine tremor loose stools renal impairment hypothyroidism weight gain acne
69
lithium toxicity?
0.4-1 mmol/l coarse tremor, n/v, ataxia and cerebellar signs and confusion
70
precipitants of lithium toxicity?
dehydration Thiazides, NSAIDs deteriotating renal function
71
how does valproate work?
inhibition of ca/na channels, which enhances inhibitory GABA and reduces excitatory glutamate
72
when is valproate effective?
acute mania
73
valproate side effects?
vomiting alopecia liver dysfunction pancreatitis retention of fat oedema appetite increase tremor enzyme inducer
74
carbamazepine side effects?
CYP4%0 inducer Atazia, diplopia Bone marrow suppressor Steven Johnson Aplastic anaemia Na- hyponatraemia Teratogenic
75
benzos used for?
anxiolytics, hypnotics, minor tranquiliser, alcohol withdrawal, anticonvuslant, muscle relaxant
76
benzos bind to?
BZP at GABA A receptor
77
abrupt withdrawal of benzos can cause?
delirium, convulsions, nausea, dizziness, hyperacusis, tinnitus, depersonalisation
78
additional aids to maintain abstinence?
acamprosate- reduce cravings naltrexone disulfiram- induces severe reaction if consumed risk of fulminating hepatitis
79
pregabalin is used for?
anxiolytics, seizures and neuropathic pain, binds to voltage gated calcium channels
80
buspirone is used for?
anxiolytic GAD, partial agonist 5HT1a receptors

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