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Positive and negative symptoms of schizophrenia
- Positive symptoms: hallucinations (auditory/visual), delusions, disorganized speech (formal thought disorder)
- Negative symptoms: lack of emotional response, lack of motivation, lack of interaction
Medications that we learn about help (positive/negative) symtpoms of schizophrenia more
Subtypes of schizophrenia
- Catatonic: alternating periods of immobility and excited agitation
- Paranoid: delusions of grandeur
- Hebephrenic: silly and immature emotionality with disorganized behavior
- Undifferentiated: doesn't meet criteria of other subtypes
Disorganization of cells in which brain region is found in schizophrenia?
Dopaminergic cells are very commonly found in which two brain structures?
Mesostriatal dopaminergic cells: What are they, what illnesses associated with them?
- Go from substantia nigra to striatum
- Associated with Parkinson's
Mesolimbic dopaminergic cells: What are they, what illnesses associated with them?
- Go from VTA to limbic system
- Schizophrenia and drug abuse
Mesocortical dopaminergic cells: What are they, what illnesses associated with them?
- Go from VTA to cortex
- Negative symptoms of schizophrenia
Antipsychotics tend to be antagonists of which 2 receptors?
D1 and D2 receptors are (ionotropic/metabotropic)
Neurodevelopmental model of schizophrenia and how it explains positive and negative symptoms
- Decrease in innervation of VTA from PFC (reduced mesocortical function), associated with negative symptoms
- This removes inhibitory feedback on limbic structures, causing positive symptoms
Blockade of both D2 and 5-HT2 receptors - advantage?
- In striatum, 5-HT stimulation of 5-HT2 receptors blocks dopamine. So 5-HT2 blockade increases dopamine in striatum
- 5-HT2 blockade doesn't have much effect in limbic system
- D2 blockade in striatum leads to movement disorder side effects; a drug that blocks 5-HT2 and D2 antagonizes dopamine in limbic system but not as much in striatum; REDUCED MOVEMENT DISORDER SIDE EFFECTS
D2 blockade leads to ___________ side effects
In which brain area does D2 blockade lead to movement disorder side effects?
- Phenothiazines (such as chlorpromazine)
- Butyrophenones (such as halperidol)
Side effects of old antipsychotics
- Orthostatic hypotension
- Anticholinergic effects
- Extrapyramidal side effects
4 extrapyramidal side effects associated with old antipsychotics
- Akathisia: internal restlessness
- Acute dystonia: spasming of a muscle group
- Parkinsonism: tremor, muscle rigidity
- Tardive dyskinesia: late acting, repetitive, uncontrollable movements (often in face)
To reduce Parkinsonian side effects, use ____________. Why does this work? These drugs also help with what other side effect of old antipsychotics?
- Blocking D2 with antipsychotic like the degeneration of DA cells in substantia nigra in Parkinson's, leading to Parkinsonian side effects
- Loss of DA in substantia nigra --> less inhibition of ACh in striatum
- Anticholinergics block ACh, reducing symptoms
- Anticholinergics also help with acute dystonic reactions
Compazine: What is it?
Old generation phenothiazine
Compazine: What does it do?
Reduces nausea/vomiting by blocking D2 receptors
Someone gets an acute dystonic reaction but never had psychosis. What was this person on and why? How do you reduce these side effects?
- Reduce nausea and vomiting
- Reduce acute dystonia with anticholinergics
Haldol-D: What is it? What are advantages and disadvantages?
- Haldol-decanoate; slow IM form of Haldol, has a very long half-life (couple of weeks or so)
- Advantages: Ensures patient receives medication, allows you to give ~1 injection per month (easier than a pill everyday)
- Disadvantages: You can't stop once you're on it; if you have a severe side effect, sucks to suck
Common side effect of new generation antipsychotics?
Metabolic syndrome side effects (weight gain and other risk factors for heart disease/diabetes)
A "truly different" antipsychotic; helpful, but many side effects and potentially dangerous
A new generation antipsychotic that has also been approved by the FDA for depression treatment