BB2Revision9 Flashcards
Peak age of MS onset is between [] years.
The rate of MS in [males / females] is increasing rapidly while the [female / male] rate of MS has remained stable.
Peak age of MS onset is between 20-40 years.
The rate of MS in females is increasing rapidly while the male rate of MS has remained stable.
Deficiency in which vitamin is associated with MS? [1]
Vitamin D - theres a geographical distribution
Describe the histopathological changes that occur in MS [3]
- Perivenular inflammation
- Demyelination: ingested by macrophages
- Gliosis (axons replaced by scar tissue)
Which viral infection is assocaited with MS? [1]
Infection from Epstein-Barr Virus
(no evidence of infection means have minimal chance of MS)
What are oligoclonal bands and how are they used in the diagnosis
Oligoclonal bands:
- IgG unique to CSF: indication that there is an immune process being driven in the CNS.
- Very consistent finding for patients with MS
- Take samples from CSF (lumbar puncture) & blood and compare
The effect of which genetic region dwarfs that of any other genetic region associated with MS? [1]
HLA
(But still very multi-gene implicated)
Describe the signs and symptoms of MS [8]
Motor - spasticity, weakness and gait abnormalities.
Sensory - positive (pins & needles) and negative sensory phenomena (loss of sensation).
Cerebellum - inco-ordination and unsteady gait.
Brain Stem - diplopia, vertigo, nystagmus, dysarthria
Optic Nerves - optic neuritis (blurred vision)
Bladder and Bowel - incontinence
Higher Functions - depression, poor concentration, forgetfulness, etc.
Fatigue
All patients present differently. Not going to be all of them
Describe the different clinical subtypes of MS [3]
Primary progressive MS:
* Steady increase in disability without attacks
Relapsing-remitting MS
* Unpredicatable attacks which may or maynot leave permanent deficits followed by periods of remission
Secondary progressive MS
* Initial relapsing-remitting MS that suddenly begins to have a decline without periods of remission
Describe the approaches of treatment for MS [2]
Immunomodulatory/immunosuppressant:
* Mainstay of traditional treatment
* dampens down the immune system
Induction therapy
* “Reset” the immune system
* Higher risk (in the short term)
* Long-lasting disease remission off treatment
A 26 year old female, with previous history of myelitis, presents with double vision on looking to the left.
Internuclear ophthalmoplegia
To meet the criteria for diagnosis of schizophrenia, the patient must have experienced at least two of the which symptoms :[5]
What else needs to occur? [1]
Two of the following:
* Delusions
* Hallucinations
* Disorganized speech
* Disorganized or catatonic behaviour
* Negative symptoms (i.e. affective flattening, avolition…)
At least one of the symptoms must be the presence of delusions, hallucinations, or disorganized speech.
The problems reported must not be attributable to another condition.
genetic pathophysiology of schizophrenia
Name three genes that are strongly implicated with schizophrenia [3]
Schizophrenia is a complex polygenic disorder:
- Dysbindin
- Neuregelin I
- DISC 1
- BDNF (brain derived neurotrophic factor)
- COMT (catechol-O –methyltransferase)
- DAOA (D-amino acid oxidase activator)
genes associated with schizophrenia
Describe the role of neuregulin 1, DISC 1 and dysbindin [3]
Neuregulin 1 – involved in synaptic plasticity and myelination
Dysbindin – may affect dopamine D2 receptor levels and glutamate and GABA transmission
DISC1 – associated with neurodevelopment and also signalling in corticolimbic areas
Describe the structural changes of brain in schizophrenia patients [3]
Larger ventricles and
smaller mesial temporal lobe structures:
- Ventricular enlargement is around 25%
- Overall reduction in brain volume of around 2%
- Greater reduction in grey matter compared to normal populations
Schizophrenic patients often have a decreased activation in which part of the brain? [1]
Decreased activation mainly in dorsolateral prefrontal area
What is the name of this test [1]
Wisconsin Card Sorting Test
Failure to properly pass the Wisconsin Card Sorting Test would indicate what? [1]
What does Wisconsin Card Sorting Test test? [1]
Frontal lobe dysfunction
assess preservation and abstract thinking in subjects
Pathophysiology of schizophrenia
Describe the impact of schizophrenia on synaptic pathways [2]
Neurodevelopmental link:
Associated with decreased synaptic spines and decreased dendritic complexity in the cortex
This occurs due to abnormalities in the formation and maturation of brain circuits
C
Pathophysiology of schizophrenia
Describe the link between schizophrenia and neuroinflammation:
- During pregnancy? [2]
- In specific areas of the brain? [1]
- Which cell types become activated in SCH patients? [1]
During pregnancy:
* Prenatal viral infection and increased level of cytokines during pregenacny increase risk of SCH in offspring
- Pro-inflammatory cytokines are elevated in the prefrontal cortex of SCH patients
- Activated microglia are present in the brains of SCH patients within a few years of the disease onset
Schizophrenia, white matter and myelination
Describe the relationship between SCH and white matter myelination in the brain [2]
Reduced oligodendrocyte density in SCH
Key molecules regulating myelination are differentially expressed in SCH (e.g. neuregulin 1 – which is also a genetic hit)
Dopaminergic pathways in the central nervous system
Describe the effect of SCH on mesocortical and mesolimbic patients
Mesolimbic is hyperactive
Mesocortical is hypoactive
SCH management
All drugs used at present to treat SCH
act as [agonist or antagonist] at that which receptors? [2]
All drugs used at present to treat SCH
act as antagonist at that D2 receptors
Gray matter loss is widespread in adolescents with schizphrenia.
What does this mean abnormalities in? [2]
Patients have abnormalities in:
- maturation of the brain
- the stabilisation of neural networks
30% schizophrenic patients do not respond to treatment. Which drug would you provied for those who have drug resistance? [1]
Clozapine
Name a risk of clozapine treatment [2]
agranulocytosis: increases chance of infection
Non-pharmacological approaches for SCH? [3]
- Cognitive Behavioural Therapy
- Cognitive remediation
- Family therapy
These do not replace the pharmacological treatment
Non-pharmacological approaches for SCH? [3]
- Cognitive Behavioural Therapy
- Cognitive remediation
- Family therapy
These do not replace the pharmacological treatment
Typically how long does drug treament for SCH take before symptoms are relieved? [1]
What is key to note about drug treatment and SCH? [1]
Improvement of symptoms takes 2-3 weeks
30% of patients do not respond to treatment - drug resistance.
·
The drugs used to treat schizophrenia are [] receptor antagonists [1]
They can be divided into typical and atypical drug treatments; what are the difference between them?
The drugs used to treat schizophrenia are D2 (dopamine) receptor antagonists
Typical:’ are older and cause generalised dopamine receptor blockade.
Atypical: are more selective in their dopamine blockade and also block serotonin 5-HT2 receptors.
Atypical antipsychotic drugs target which receptor/s
D1 receptors
D2 receptors
D1 & D2 receptors
D1 & 5-HT2 receptors
D2 & 5-HT2 receptors
Atypical antipsychotic drugs target which receptor/s
D1 receptors
D2 receptors
D1 & D2 receptors
D1 & 5-HT2 receptors
D2 & 5-HT2 receptors
Name 5 typical antipyschotics
chlorpromazine, thioridazine,
fluphenazine, haloperidol, flupenthixol
Why are typical anti-pyschotics commonly have poor compliance? [1]
The lack of selectivity of action of the drugs used, results in a wide range of unwanted effects, which decrease compliance.
Describe the effect of typical anti-physchotics on positive and negative symptoms [1]
Improve positive symptoms
Little/no efficacy on negative symptoms
Clozapine blocks [] receptors with high affinity
Aripiprazole is a partial [] at presynaptic D2 receptors but an [] at D2 postsynaptic receptors
Clozapine blocks D4 receptors with high affinity
Aripiprazole is a partial agonist at presynaptic D2 receptors but an antagonist at D2 postsynaptic receptors
Name 2/6 atypical anti-psychotics used to treat SCH [6]
risperidone, olanzapine, clozapine, quetiapine, paliperidone, aripiprazole
Atypical anti-psychotics target which receptors? [2]
Antagonists at:
- D2 receptors
- 5-HT2A receptors
Name 3 extrapyramidal effects that occur due to antipsychotic drugs. [3]
Why do these occur? [1]
Extrapyramidal effects (EPS):
* acute dystonias
* parkinsonism
* tardive dyskinesia
Approx. 60% D2 receptor occupancy required for
antipsychotic efficacy; if >80% D2 receptors are blocked, then potential for EPS
Explain why antipsychotic drugs may cause sexual dysfunction, galactorrhoea or amenorrhoea?
Block dopamine receptors; causes a rise in prolactin
Which anti-psychotics can be adminstered by IM injections? [2]
fluphenazine decanoate
haloperidol decanoate
Describe the difference in AEs between atypicals and typical anti-pyschotics
Atypicals
* Less EPS
* Less cardiac toxicity (QT segment prolongation)
* Less hyperprolactinaemia
* Weight gain
* Hyperglycaemia, diabetes
* Insulin resistance
* Dyslipidaemia
* Cardiovascular disease
Typicals:
EPS (dystonia, parkinsonism…)
Tardive dyskinesia
Weight gain
QT interval prolongation
Sudden death
Hyperprolactinaemia
Describe the difference in AEs between atypicals and typical anti-pyschotics
Atypicals
* Less EPS
* Less cardiac toxicity (QT segment prolongation)
* Less hyperprolactinaemia
* Weight gain
* Hyperglycaemia, diabetes
* Insulin resistance
* Dyslipidaemia
* Cardiovascular disease
Typicals:
EPS (dystonia, parkinsonism…)
Tardive dyskinesia
Weight gain
QT interval prolongation
Sudden death
Hyperprolactinaemia
Explain what tardive dyskinesia is and the length of the AE [2]
Involuntary movements of the lips, jaw, face; grimacing, constant chewing, tongue thrusting; rapid involuntary limb movements
typical antipsychotics,
taken for longer than a few months/years
In some patients it may be possible to overcome it
Describe what neuroleptic malignant syndrome is a combination of [6]
Due to typical anti-psychotics
hyperpyrexia
muscle rigidity
tremor
confusion
autonomic instability
Explain what future SCH drug targers are [3]
The NMDA glutamate receptor:
- Decreased glutamatergic transmission in SCH- hypoglutamatergic state in cortex
- May be possible to potentiate activity of glutamatergic receptors in future
Prolonged used of typical anti-psychotics may leda to which syndrome? [1]
neuroleptic malignant syndrome
Alchohol / ethanol decreases the effect of which channel to cause psychodepression?
Na+
K+
Cl-
Ca2+
H+
Alchohol / ethanol decreases the effect of which channel to cause psychodepression?
Na+
K+
Cl-
Ca2+
H+
DOES NOT act on a single specific receptor protein.
Which of the following inhibits dopamine uptake?
Caffeine
MDMA
Alcohol
Cannabis
Cocaine
Which of the following inibits dopamine uptake?
Caffeine
MDMA
Alcohol
Cannabis
Cocaine
What does the yellow rectangle represent?
Caffeine
MDMA
Alcohol
Cannabis
Cocaine
What does the yellow rectangle represent?
Caffeine
MDMA
Alcohol
Cannabis
Cocaine
Which of the following is an adenosine antagonist?
Caffeine
MDMA
Alcohol
Cannabis
Cocaine
Which of the following is an adenosine antagonist?
Caffeine: adenosine promotes sleep
What are the 3 mechanisms of acton of MDMA use? [3]
3 key functions:
I. Stimulate release of catecholamines
II. Inhibit catecholamine recapture by the uptake system
III. Inhibit monoamine oxidase (MAO) activity
Which specific receptors do atypical anti-pyschotics target?
5-HT1A
Na
5-HT2A
D1
Which specific receptors do atypical anti-pyschotics target?
5-HT1A
Na
5-HT2A strong antagonists; weak D2 receptors
D1
Which of the following anti-pyschotics is particularly useful for negative symptoms?
Risperidone
Quetiapine
Aripiprazole
Clozapine
Olanzapine
Which of the following anti-pyschotics is particularly useful for negative symptoms?
Risperidone
Quetiapine
Aripiprazole
Clozapine
Olanzapine
Which of the following anti-pyschotics is a partial agonist at pre-synaptic D2 but an antagonist at post-synaptic D2?
Risperidone
Quetiapine
Aripiprazole
Clozapine
Olanzapine
Which of the following anti-pyschotics is a partial agonist at pre-synaptic D2 but an antagonist at post-synaptic D2?
Risperidone
Quetiapine
Aripiprazole
Clozapine
Olanzapine
Which of the following may cause an increased risk of infection?
Risperidone
Quetiapine
Aripiprazole
Clozapine
Olanzapine
Which of the following may cause an increased risk of infection?
Risperidone
Quetiapine
Aripiprazole
Clozapine
Olanzapine
Clozapine targets which receptor
D1
D2
D3
D4
Clozapine targets which receptor
D1
D2
D3
D4
Which statement best explains the pathophysiology of schizophrenia?
A. It is due to a lack of dopamine
B. It is due to antibodies to the dopamine receptors
C. It is due to a lack of sensitivity of dopamine receptors
D. It is due to excess dopamine
Which statement best explains the pathophysiology of schizophrenia?
A. It is due to a lack of dopamine
B. It is due to antibodies to the dopamine receptors
C. It is due to a lack of sensitivity of dopamine receptors
D. It is due to excess dopamine
Schizophrenia is believed to be due to excess dopamine in the area of the mesolimbic system.
A 30-year-old female presents to the clinic complaining of irregular menses. She has been having irregular menstrual cycles for the past two years. The patient has a history of schizophrenia but has been stable on her current antipsychotic medication. She discontinued oral contraceptives and has abstained from both alcohol and nicotine for approximately one year as she and her husband are planning to start a family. The physical exam is unremarkable and the patient denies suicidal or homicidal ideations, denies auditory or visual hallucinations, cognition and judgment are intact. What is the most likely hormonal abnormality causing this patient’s symptoms?
A. Increased gonadotropin hormone secretion
B. Decreased human growth hormone secretion
C. Increased prolactin secretion
D. Decreased thyroid hormone production
A 30-year-old female presents to the clinic complaining of irregular menses. She has been having irregular menstrual cycles for the past two years. The patient has a history of schizophrenia but has been stable on her current antipsychotic medication. She discontinued oral contraceptives and has abstained from both alcohol and nicotine for approximately one year as she and her husband are planning to start a family. The physical exam is unremarkable and the patient denies suicidal or homicidal ideations, denies auditory or visual hallucinations, cognition and judgment are intact. What is the most likely hormonal abnormality causing this patient’s symptoms?
A. Increased gonadotropin hormone secretion
B. Decreased human growth hormone secretion
C. Increased prolactin secretion
D. Decreased thyroid hormone production
Which area of the brain sets the urgency with which a movement is chosen and executed?
Prefrontal cortex
Premotor cortex
Posterior parietal cortex
Primary motor cortex
Supplementary motor area
Which area of the brain sets the urgency with which a movement is chosen and executed?
Prefrontal cortex
Premotor cortex
Posterior parietal cortex
Primary motor cortex
Supplementary motor area
