Case of unfair diagnosis Flashcards
activation of transmembrane tyrosine kinase receptors?
growth factor binds to receptor causing dimerisation and autophosphorylation causing downstream activation of signalling cascade
mutations causing dysregulation of tyrosine kinase receptor?
ligand independent firing, autocrine growth factors
which tyrosine kinase growth factors are altered in human tumours?
erb b2, her2, neu, egfr
common mechanism of resistance to TKIs?
T790 mutation
first line for tyrosine kinase mutations?
osimertinib
lung cancers can often present with?
recurrent chest infections
pleural effusion
how to geta biopsy for lung cancer?
EBUS and tbna
appearance of adenocarcinoma?
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
squamous cell carcinoma signs?
centrally, bronchial trees, squamous cell keratinisation, desmosomes
p40+. p63+, CK5/6+
PDL1 mutation
cavitate and sometime haemorrhage
small cell (neuroendocrine cells)
very blue cells, small cells, smudged nuclei
CD56, chromogranin positive
TTF1 nuclear - usually present in lungs
mesothelioma?
WT-1, calretinin positive
TTF-1, MOC31, napsin, p40 negative
aggressive, encasement of lung
Metastasis to the lungs?
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
pseudogenes?
shares a large amount of DNA with another gene
14 hallmarks of cancer?
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
MEN2 is caused by which gene mutation?
RET
medullary thyroid cancer -90%
phaechromocytoma-50
parathyroid adenoma- 20-30%
familial medullary thyroid cancer- 100% risk
MEN2B?
same risk for medullary thyroid/phaechromocytoma
but other abnormalities 40-40
mucosal neuromas
marfanoid
toxic megacolon
>95%= always de novo
most frequent somatic mutation?
LOF- TP53 85% of tumours
most frequent somatic mutation?
LOF- TP53 85% of tumours somatic
BRCA1 is?
more common as germline
BRCA1?
BREAST CANCER ER NEGATIVE 80% OF THE TIME
Li Fraumeni syndrome?
inherited alteration in TP53
role of TP53?
DMA damage repair
induction of apoptosis
cellular metabolism
transcription
induction of G1 arrest
treatment for angiogenesis?
inhibitors of VEGF signalling
treatment for invasion/metastasis?
inhibitors of HGF/c-met
treatment for promoting inflammtion?
selective anti-inflammatory drugs
target for replicative immortality?
telomerase inhibitors
target for avoiding immune destruction
immune activating anti-CTLA4 mAB
target for evading growth suppressors?
cyclin-dependent kinase inhibitors
target for proliferative signaling?
EGFR inhibitors
target for deregulating cellular epigenetics?
aerobic glycolysis inhibitors
target for resisting cell death?
proapototic BH3 mimetics
target for genome instability?
PARP inhibitors
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
dotheipin requires?
more ecg monitoring as it is cardiotoxic
anticholinergic effects
constipation
urinary retention
cognitive effects
dry mouth
akathisia can be treated with?
propanolol
EXAMPLES OF SSRIS?
fluoxetine, paroxetine, setraline, citalopram, escitalopram
indications for SSRIs?
depression, anxiety disorders, panic disorder, obsessive compulsive disorder, PTSD
half life of ssris?
paroxetine-20 hours
fluoxetine-2/4days
fluoxetine side effect
agitation
mirtazapine is?
noradrenergic and specific serotonergic antidepressant
alpha 2 receptor antagonist
helps with insomnia
make neurons activated
downside of mirtazapine?
more hungry
mirtazapine helps by?
antidepressant, anxiolytic, sleep restoring, no sexual dysfunction no gi problems
adverse effects of tricyclics?
dry mouth, constipation, urinary retention, cognitive effects, psychotropic effects agitation and nightmares, sexual dysfunction, akathisia, muscle twitches, cardiac arrhythmias
overdose of tricyclics?
confusion, tachycardia/arrhythmias, hypotension, mydriasis seizures, coma and cardiorespiratory arrest
what is particularly effective for mixed depression and anxiety?
venlafaxine
side effects on SNRI venlafaxine?
headache, nausea, hypertension, discontinuation syndrome
duloxetine - no concerns of hypertension
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.
how does NASSA work mirtazaoine?
release of seretonin and noradrenaline via alpha 2 receptors on presynaptic neurone
SNRI examples?
venlafaxine, duloxetine
MAOI examples?
moclebamide, phenelzine
What does dopamine control?
executive function, lactation, motivation, motor control, reward, nausea
dopamine pathways?
mesocortical- prefrontal cortex motivation negative symptoms
mesolimbic-nucleus accumbens
positive symptoms
nigrostriatal- caudate nucleus/putamen
parkinsonian symptoms
tuberoinfundibular-pituitary gland- hyperprolactinaemia
typical antipsychotics are?
d2 receptor antagonist so help with positive symptoms
typical antipsychotic side effects?
too little dopamine in tuberofundibular- hyperprolactinaemia
amenorrhoea, sexual function, galactorrhoea and osteoporosis
nigrostriatal- extrapyramidal effects
seretonin hypothesis?
hallucinogenic drugs LSD structurally similar to serotonin
glutamate hypothesis?
Phencyclidine- glutamate agonist which produces schizophrenia like symptoms, abnormal glutamate activity in schizophrenia
typical antipsychotics neurological side effects?
extrapyramidal symptoms- parkinsonism, akathisia, dystonia
tardive dyskinesia
typical antipsychotic examples?
haloperidol, chlorpromazine
atypical antipsychotics details?
not specific for d2 receptors, can act on seretonin
risperidone, olanzapine, quetiapine, aripiprazole
what are the problems with atypicals?
weight gain and metabolic syndrome particularly olanzapine
muscarinic side effects?
dry mouth, constipation, urinary retenion, blurred vision, dry eyes, tachycardia, dyspepsia, dizziness, impaired cognition/memory
side effects of adrenergic antagonist alpha blockers?
orthostatic hypotension, palpitation, sexual dysfunction and vertigo
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
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
Clozapine binds with high affinity to?
M1, 5HT21, H1, a1 and a2
rapid tranquilisation when patient aggressive?
antipsychotics- haloperidol, olanzapine
benzos- lorazepam or midazolam
mood stabiliser?
lithium
valproate
lamotrigine
carbamazepine
lithium method of action?
second messenger- inhibition of inositol,
regulation of gene expression, protein kinase c
lithium side effects?
polydipsia, polyuria
nauseau
fine tremor
loose stools
renal impairment
hypothyroidism
weight gain
acne
lithium toxicity?
0.4-1 mmol/l
coarse tremor, n/v, ataxia and cerebellar signs and confusion
precipitants of lithium toxicity?
dehydration
Thiazides, NSAIDs
deteriotating renal function
how does valproate work?
inhibition of ca/na channels, which enhances inhibitory GABA and reduces excitatory glutamate
when is valproate effective?
acute mania
valproate side effects?
vomiting
alopecia
liver dysfunction
pancreatitis
retention of fat
oedema
appetite increase
tremor
enzyme inducer
carbamazepine side effects?
CYP4%0 inducer
Atazia, diplopia
Bone marrow suppressor
Steven Johnson
Aplastic anaemia
Na- hyponatraemia
Teratogenic
benzos used for?
anxiolytics, hypnotics, minor tranquiliser, alcohol withdrawal, anticonvuslant, muscle relaxant
benzos bind to?
BZP at GABA A receptor
abrupt withdrawal of benzos can cause?
delirium, convulsions, nausea, dizziness, hyperacusis, tinnitus, depersonalisation
additional aids to maintain abstinence?
acamprosate- reduce cravings
naltrexone
disulfiram- induces severe reaction if consumed
risk of fulminating hepatitis
pregabalin is used for?
anxiolytics, seizures and neuropathic pain, binds to voltage gated calcium channels
buspirone is used for?
anxiolytic GAD, partial agonist 5HT1a receptors
