Mental health + Parkinsons Flashcards
How is schizophrenia seen in an MRI scan of the brain?
Ventricular dilation due to loss of brain tissue
What are the three main types of symptoms in schizophrenia?
Cognitive
Positive
Negative
State some positive symptoms of schizophrenia
Hallucinations
Delusions
Disorganised speech
State some negative symptoms of schizophrenia
Reduced motivation
Reduced emotion
Lack of interest
Lack of pleasure
State some cognitive symptoms of schizophrenia
Lack of attention
Lack of working and verbal memory
What are the four dopaminergic pathways in the brain?
Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular
What is the mesolimbic pathway associated with?
Mediates pleasure, reward, motivation
Hyperactivity of dopamine mediates positive psychotic symptoms
D2 antagonists treat positive symptoms
What is the mesocortical pathway associated with?
Cognitive function, emotion
Decreased dopamine responsive for negative symtpoms
What is the nigrostriatal pathway associated with?
Motor control
Parkinsonian symptoms
What is the tuberoinfundibular pathway associated with?
Inhibition of prolactin release
Malfunction in which brain circuit are cognitive symptoms associated with?
Dorsolateral prefrontal cortex
What is the dopamine theory for schizophrenia?
Increased dopamine in subcortical pathways -> psychotic symptoms
Agonists of dopamine e.g. amphetamine induce psychotic symptoms
What is the glutamate theory of schizophrenia?
NMDA hypofunction is induced by genetic and non-genetic factors instilled in the brain in early development triggers psychosis in adulthood.
NMDA antagonist phencyclidine lead to positive, negative, cognitive and affective symptoms
Which of the two classes of antipsychotics causes most EPS?
Typicals
Name a typical antipsychotic
Haloperidol
Name an atypical antipsychotic
Clozapine
What are the major side effects of atypicals?
Weight gain
CVD
Diabetes
Which class of antipsychotics is ineffective at managing negative symptoms?
Typical
Which class of antipsychotics is associated with motor side effects and why?
Typicals because they have high affinity for dopamine D2 receptors not only in areas needed but else where so can affect motor function and cause tardive dyskinesia
What percentage of receptor occupancy is required for effective antipsychotic effect?
> 65%
What is the effect of >78% D2 receptor occupancy?
EPS
What is the effect of over 70% D2 receptor occupancy?
Hyperprolactinaemia
Which antipsychotic is associated with most weight gain?
Olanzapine
What are the treatment options for a schizophrenic patient in the prodromal phase?
Offer CBT +/- family intervention. Do not offer antipsychotic
What are the treatment options for patient with first episode of schizophrenia?
Offer antispsychotic in conjunction with CBT after ruling out other causes of symptoms
How is a subsequent actue episode of schizophrenia treated?
Treated as first episode schizophrenia. May need to switch therapy e.g. from typical to atypical
What is “treatment resistant schizophrenia” defined as and how is it treated?
Schizophrenia resistant to treatment with two different antipsychotics, one of which being an atypical
What are the 4 different types of EPSE?
Pseudo-parkinsonism
Akathisia
Dystonia
Tardive dyskinesia
Which type of EPSE are anticholinergics not useful for?
Akathisia and tardive dyskinesia
What side effects are associated with clozapine?
VTE Constipation Sedation Hypersalivation Myocarditis and cardiomyopathy neutropenia and agranulocytosis Metabolic syndrome
Describe the pathophysiology of Parkinson’s disease
Chronic, progressive neurodegenerative disease
Degeneration of dopaminergic neurones in the nigro-striatal pathway
Presence of Lewy bodies in neurones
Changes in GABA glutamate pathway
What are the motor symptoms associated with Parkinson’s disease?
Tremor
Rigidity
Bradykinesia
List some non-motor symptoms associated with Parkinson’s
Swallowing and speech problems Constipation Urinary problems Drooling, loss of smell Lewy body dementia
When should drug treatment be initiated in Parkinson’s?
When motor symptoms affect patients ability to function on a daily basis
What does drug treatment for Parkinson’s aim to do?
Increase dopamine levels in the brain
What are the main 3 initial treatment options for parkinson’s disease?
Levodopa - most effective
MAO-B inhibitor
Dopamine agonists
Why does levodopa need to be combined with dopa-decarboxylase?
To prevent the peripheral metabolism of levodopa to dopamine
Name a MAO-B inhibitor
Rasagiline
How do MOA-B inhibitors work?
Inhibit the metabolism of dopamine -> increase of dopamine at receptors
What are the two classes of dopamine agonists used in Parkinson’s?
Ergot and non-ergot
What are some of the side effects associated with dopamine agonists?
Sudden sleep onset
N + V
rarely, dopamine dysregulation syndrome (gambling, hypersexuality, binge eating)
Which drug are COMT inhibitors used in combination with and how do they work?
Levodopa. They prevent the metabolism of levodopa to 3-O-methyldopa
Name a COMT inhibitor
Entacapone
Which class of drugs in Parkinson’s disease is avoided in elderly due to risk of falls
Anticholinergics
In which circumstances is duodopa used?
For PD with severe motor fluctuations and dyskinesia
How is duodopa administered?
It is an intestinal gel administered using pump via PEG tube i.e. invasive
Which dopamine agonist can be given as a subcut injection?
Apomorphine - useful for on-off fluctuations
How can early morning bradykinesia in PD be treated?
Dispersible levodopa taken on wakening or night-time dose of dopamine agonist or MR levodopa
How can dyskinesia be treated in PD?
Reduce levodopa dose
Add amantadine
What is amantadine used for in PD?
Treatment of dyskinesia in late disease. It is a glutamate antagonist at NMDA receptor
Which drug in the treatment of bipolar disorder can’t be used in mania?
Lamotrigine
Which drug in the treatment of bipolar disorder can’t be used in women of child-bearing potential?
Valproate
Can lithium be used in pregnancy?
Yes - sometimes taking pregnant woman off lithium can lead to them becoming manic during pregnancy so plan needs to be made
How often do lithium levels need to be taken?
12hrs post dose, check weekly until stable then 3 monthly for first year
How is lithium cleared?
Kidneys so can lead to nephrotoxicity
What is the maximum level of lithium that should be given?
1mmol/l
Ideally range of 0.4-0.8mmol/l
Which class of antidepressants interacts with tyramine (found in cheese)?
Monamine oxidase inhibitors
What is the monoamine hypothesis in depression?
Depressive disorders are due to a depletion and mania to an excess provision of monoamine neurotransmitters at one or more CNS sites
Antidepressants correct this depletion by increasing the availability of monoamines at post-synaptic receptors
When taking antidepressants, the effects on transmitters are immediate and antidepressant effects take several weeks to arise. Why?
Because when you first start taking antidepressants, transporters are blocked. This increases serotonin around the cell body which increases the activation of autoreceptors. This then reduces cell firing and reduces the release of serotonin. This is the opposite to what you want. However, after taking antidepressants for a few weeks, there is chronic activation of the autoreceptors and they become downregulated.
Inhibition on cell-firing is lost so cell-firing is increased
What is the first line class of antidepressants?
SSRIs
Name a SSRI
Sertraline
Citalopram
Fluoxetine
Name a SNRI
Venlafaxine
Which antidepressant drug can be used if first-line doesn’t work?
Mirtazapine - considered to be a better tolerated antidepressant
Which two side effects are linked to mirtazapine?
Sedation
Weight gain
Which class of antidepressants does amitriptyline belong to?
Tricyclics
Which class of antidepressants requires strict dietary requirements?
Monoamine oxidase inhibitors - cannot eat food containing tyramine
How long does it take for improvement in depressive symptoms to take place after starting an antidepressant?
4 weeks for full effect, 6 weeks in the elderly
What is the most common combination of antidepressants?
mirtazapine and venlafaxine
Antipsychotics can be used on their own in depression. True or false?
False
What is meant by augmentation in depression?
Adding lithium or an antipsychotic e.g. olanzapine
Is St John’s Wort recommended in depression?
No
How is antidepressant treatment stopped?
Continued for 6 months after patient gets better at the dose they got better at. May need to continue for longer depending on history, side effects and risk of relapse. Then gradual reduction needed to prevent discontinuation symptoms
What are the 7 adverse effects of clozapine?
VTE Sedation Hypersalivation Constipation Myocarditis and cardiomyopathy Metabolic syndrome Neutropenia and agranulocytosis
How are myocarditis and cardiomyopathy treated?
Stop treatment and refer
How are myocarditis and cardiomyopathy monitored?
Daily RR, pulse, BP and temp
Weekly FBC, CRP, ECG
How are neutropenia and agranulocytosis monitored?
Flu-like symptoms
How many brands of clozapine are there and can the patient switch between them?
3 brands - bioequivalent so yes can switch without dose adjustment
Does the risk of agranulocytosis increase or decrease with prolonged clozapine use?
Decreases
Describe the traffic light system for dispensing clozapine
Red - stop, FBC daily until stable
Amber - continue but monitor FBC twice weekly
Green - dispense
How often are FBC needed for clozapine?
1 weely for first 18 weeks, fortnightley for 34 weeks. Monthly until stopped
How much clozapine can be dispensed in weekly FBC monitoring?
10 days from last blood count
How much clozapine can be dispensed in fortnightly FBC monitoring?
21 days from last blood count
How much clozapine can be dispensed in monthly FBC monitoring
42 days from last blood count
What does the patient need to be told if they miss a dose of clozapine?
If missed for more than 48hrs, re-titrate dose, can’t continue maintenance
If missed more than 3 days, blood test frequency may need to be changed
