P: Antipsychotics - Week 10 Flashcards
Is schizophrenia homogenous or heterogenous among the population?
Heterogenous. Not all schizophrenia is the same and people experience it differently
Classify schizophrenia into 5 groups based on number of episodes and level of recovery, ranking them from highest to lowest incidence
Multiple episodes, partial recovery: 28%
Chronic illness, clear deterioration: 23%
Multiple episodes, good recovery: 21%
Chronic illness, little deterioration: 20%
Single episode, good recovery: 8%
Why might drugs work for one schizophrenic patient but not another?
Because the schizophrenia can be different. Consider schizophrenia to be more like a ‘syndrome’ of disorders rather than an individual disorder
Name 4 ways we can modulate neurotransmitter function in CNS disorders (note there are others, just the one’s he mentioned though)
- modulate synthesis
- storage
- re-uptake
- receptors
What is the consequence of heavy amphetamine use? Explain (3)
Schizophrenia-like symptoms. This is evidence of the monamine theory of schizophrenia (dopamine involvement). It is though that an overabundance of dopamine NT is involved in schizophrenia, and amphetamines displace dopamine at storage centres encouraging more of it to release from nerve terminals
What incidence of the population is affected by schizophrenia? Does this differ based on culture or socioeconmic groups?
1%. No.
At what age does schizophrenia often develop?
Early age. Usually develops around the onset of puberty
Is schizophrenia generally acute or chronic?
chronic
How does having affected family members contribute to the incidence of schizophrenia development? (3)
1 affected 1st degree relative: higher
affected dizygotic twin: even higher
2 affected parents: even higher than that
If both of your parents had schizophrenic episodes, what is the likelihood you will develop it too?
about 50%
Is there an environmental aspect to the development of schizophrenia?
yes
How does the environment affect genes relating to schizophrenia?
Epigenetic mechanisms allow environmental factors to switch genes on and off and thus affect/modulate gene expression
Can recreational drug use lead to schizophrenia?
It can, but it depends on your genetic predisposition. If you are not genetically predisposed to schizophrenia it is extremely unlikely to acquire it from drugs
What proportion of schizophrenics respond well to anti-psychotic drugs?
28%
What proportion of schizophrenics respond with some/partial benefit to anti-psychotic drugs?
38%
What proportion of schizophrenics respond with little or no benefit to anti-psychotic drugs?
34%
Why might compliance be an issue with anti-psychotic drugs? (1)
Undesirable side effects such as depersonalization
What are the positive symptoms of schizophrenia? (3)
Delusions (often paranoid)
Hallucinations (voices)
Disordered thought
What symptom of schizophrenia does Randy Orton suffer from?
he hears VOICES in his head they council him they understand they talk to him
(so, hallucinations)
What are the negative symptoms of schizophrenia? (2)
Withdrawal from society/family
Flattened emotions
Which type of schizophrenia symptom responds better to medication? positive or negative?
positive
Define positive symptoms of schizophrenia
psychotic behaviours not seen in healthy people
Can schizophrenia affect movement?
Yes. Movement disorders: people with schizophrenia can have agitated body movements or catatonia (where the person does not move and does not respond to others)
Define negative symptoms of schizophrenia
associated with disruptions to normal emotion and behaviors
Define flat affect. What type of schizophrenia symptom is it
A negative symptom where a person’s face does not move or he/she talks in a dull or monotonous voice
Define avolition. What type of schizophrenia symptom is it
A negative symptom where there is a lack of ability to begin or sustain planned activities
Define Alogia. What type of schizophrenia symptom is it
A negative symptom where they speak little, even when forced to interact
What type of cognitive symptoms can schizophrenia result in? (3)
Poor executive functioning: which affects the understanding of information and decision making
Trouble focusing or paying attention
Problems with working memory: which impacts on the ability to use newly learned information
What is the proposed aetiology behind schizophrenia development?
“Dopamine Hypothesis”: schizophrenia is linked to a functional excess of dopaminergic activity
What is the pharmacological evidence for the “Dopamine Hypothesis”? (3)
Agents that enhance catecholamine release (amphetamine) can induce schizo-like symptoms
Dopamine (DA) depletion controls positive symptoms
Many useful antipsychotic drugs are antagonists at dopamine D2 receptors. (in limbic system)
What pathway do we believe makes the best target for schizophrenia treatment?
Limbic pathway (we want a blockade of D2 receptors in the limbic system)
What are 2 other neurotransmitters that have been implicated in the development of schizophrenia? Provide reasoning for both
Serotonin: LSD (agonist against CNS 5HT receptors) induced schizophrenia-like symptoms
Glutamate: several glutamate receptor antagonists have been shown to induce schizophrenia-like symptoms
How effective are anti-psychotic drugs at blocking 5HT receptors?
Effective
Do the drugs used to treat schizophrenia bind to a single receptor or many receptors?
Bind to many different kinds or receptors - this is why you get all these side effects
True/False: all anti-psychotic drugs target the dopamine D2 receptor
true. While they have different inhibitory profiles, all anti-psychotic drugs target the D2 receptor in some respect
Name 2 typical/classical anti-psychotic drugs. What generation of anti-psychotics are they?
Chlorpromazine
Haloperidol
They are 1st generation anti-psychotics
Where do typical anti-psychotic drugs act? (2)
Antagonists at D2 receptors
Also antagonists at other receptors
How long does the onset of anti-psychotic action take for typical anti-psychotics? What does this suggest?
Several weeks. This suggests that there are secondary changes to the receptor blockade (i.e. there are changes in neuronal wiring, which you wouldn’t see straight away)
Describe the spectrum of activity of atypical anti-psychotic drugs
Diverse
When are atypical antipsychotic drugs typically useful?
When ‘classical’ drugs are not appropriate or produce too many unwanted effects
Name 2 examples of atypical anti-psychotic drugs
Clozapine
Olanzapine
How do atypical anti-psychotics differ from typical in regards to receptor antagonism?
They tend to have more selective receptor antagonism
Are atypical anti-psychotics antagonists at dopamine D2 receptors?
yes
What receptor blockade is considered a “feature” of atypical anti-psychotics?
5HT receptor blockade
True/False: atypical anti-psychotics can be useful in tackling ‘negative’ symptoms of schizophrenia
True
How many unwanted effects can anti-psychotics cause?
Numerous
Name 2 conditions involving extrapyramidal motor disturbance and describe how they are caused
Parkinson’s-like syndrome: results from D2 antagonism in other brain regions (b/c parkinson’s is due to lack of dopamine)
Tardive Dyskinesia: involuntary movements (often face and tongue)
How can anti-psychotic drugs result in endocrine disturbance? (2)
dopamine is involved in inhibition of prolactin release.
anti-psychotic drugs therefore enhance prolactin release
What does increase prolactin release lead to? (3)
breast swelling, pain, lactation
Name 4 other notable side effects from anti-psychotic drugs
sedation: not necessarily bad
atropine-like effects: blurred vision, dry mouth, constipation
postural hypotension: alpha-adrenoceptor antagonism
weight gain: 5HT2 antagonism
