schizophrenia Flashcards
what is schizophrenia (scz)
Oscillation between normal and abnormal sense of reality and sense of reality
What is Scz characterized by
Loss of contact with reality
Disruption of thought
-Perception
-Mood
-Movement
what is Epidemiology of Schizophrenia and what is it linked to?
1/100 lifetime risk in the general population.
Signs show at around the age of 15-25(Men): This is when the prefrontal cortex usually develops.
What are is the meaning of positive and negative symptoms
Positive: presence of symptoms that are not normally there
Negative: Absence of normal symptoms
List some of the negative symptoms of SCZ
Reduced expression of emotion
Poverty of speech
Difficulty in initiating goal-directed movements
Cognitive/Memory impairment
What are the subtypes of SCZ
1.Paranoid schizophrenia
- Disorganised
3.Cationic: agitated, purposeless movement
what is Paranoid schizophrenia
Delusion and hallucination
-thought disorder, disorganized behaviour, and mood flattening are absent
what is disorganised schizophrenia
thought disorder and mood flattening
what is catatonic schizophrenia
Rare scz disorder. Symptoms can involve flipping between hyperactivity and under activity
> underactivity : significant reductions in voluntary movement
> hyperactivity: agitated, purposeless movement, exhibit unusual styles and levels of physical movement
What are the causes of SCZ
Environmental factors
Genetics
What are the environmental factors that can lead to SCZ
Social stress
-especially early in life (Post or pre natal)
Prenatal infection and famine
Obstetric and perinatal complications
Older paternal age
Cannabis use/ substance misuse
What are the pathophysiological theories of Schizophrenia
1.Dopamine hypothesis
2.Glutamate hypothesis
3.GABA hypothesis
What is the Dopamine hypothesis
That excess dopaminergic NTission in mesolimbic and striatal brain region results in schizophrenic symptoms
What is the evidence behind the dopamine theory
- Most antipsychotics block D2 receptors
- Drugs that increase dopaminergic activity aggravate or produce sycosis
- D receptor numbers increase in post-mortem brain of schizophrenics
4.Increase D receptor density
5.Successful treatment changed levels of homovanillic acid (dopamine metabolite)
What the evidence against the dopamine hypothesis
Antipsychotic drugs only partially effective for most patients
NMDA receptor (glutamate receptor) antagonists (phencyclidine) more potent
What is the glutamatergic hypothesis of schizophrenia
NMDA receptor antagonist are potent dopamine releasers
-This caused psychotic symptoms in a health human and exacerbation in patients
The treatment of SCZ with D-serine, glycine and sarcosine (NMDA receptor modulators) have therapeutic benefits in negative symptoms
What is the GABAergic hypothesis of SCZ
Decrease in GABA leads to enhanced DA neuron activation there for more DA release
what are the main targets of antipsychotic drugs
Dopamine receptor and serotonin receptor
What are the positive symptoms of SCZ
Delusions
Hallucinations
Disorganised speech
Grossly disorganized or catatonic behaviour
What is the brain regions and systems included in the dopamine hypothesis for schizophrenia
Substantial nigra
VTA
Tuberohypohyseal systems
What is the proposed mechanism of the glutaminergic hypothesis
Hypofunction of NMDA receptors on GABAergic interneuron
Leads to less inhibition of principal glutaminergic cells
Activates dopamine expressing cells
More dopamine release
What is the mechanism of the GABAergic synthesis
Deficiency in signalling in the TrkB neurotrophin receptors leads to reduced GABA synthesis in Parvalbumin-containing GABA neurons
– enhanced excitability of the pyramidal neurons in dorsal PFC
–Enhanced activation of DA neurons
which dopamine receptors does not have a role in psychosis
D1 receptos
What are the main dopamine pathways
Meso-cortical limbic pathways: Behaviour
-Nigro-striatal pathways: Voluntary movements
-Tuberoinfundibular system: Dopamine released to inhibit prolactin release
-Medullary-periventricular pathway: feeding behaviour
-Incertohypothalamic pathways: Fear conditioning
What are the two families of dopamine receptors
D1-like: D1 and D5
D2-like: D2,D3 and D4
They are all metabotropic (G-protein)
What are the mechanism of D1 and D5 receptors
D1: Increase cAMP by Gs-coupled of adenylyl cyclase expressed in the putamen, Nucleus Accumben, olfactory tubercle
How to D2 receptors work
Decrease cAMP in Gi-Coupled inhibition of adenylyl cyclase
-Inhibit Ca2+ channels: decrease neuronal activity
-Opens K+ channels
What is difference between typical and Atypical anti-psychotics
-Receptor profile
-Incidence of extra pyramidal side-effects
-Efficacy in ‘treatment-resistance’ groups
-Efficacy against negative symptoms
What are the main classes of typical antipsychotics
-Phenothiazine class
-Butyrophenone class
How many groups of the class phenothiazine are there and list some examples
Group 1: chlorpromazine; levomepromazine; promazine
Group 2: pericyazine; pipotiazine
Group 3: Fluphenazine and Prochlorperazine
What are the side effects of the Phenothiazine groups
Group 1:
-Pronounced sedative effect
-Anti-muscarinic and extrapyramidal side effects
- Hypotensive side effects
-Low clinical potency
Group 2
-Moderate sedative effect
-Severe anti-muscarinic effects
-Pronounced extrapyramidal side effects
Group 3
-Fewer sedative and anti-muscarinic effects
-Pronounced extrapyramidal side effects
What are the drugs in group 1 phenothiazines
chlorpromazine;
levomepromazine;
promazine
What are the drugs in group 2 phenothiazines
pericyazine; pipotiazine
What are the drugs in group 3 phenothiazines
fluphenazine; prochlorperazine
What drug is under the class of Butyrophenone
Haloperidol
Benperidol
List some typical anti-psychotic drugs
Clozapine
Risperidone
Aripirazole
Properties of Haloperidol
Use is limit due to severe (Extra pyramidal symptoms) EPS
-High D2 receptor affinity
-Potent
-Has hypotensive side effects
What are the positive properties of Clozapine
-Greater affinity to 5-HT than D2
-Potent D4 antagonist
-Efficient in ‘Treatment-resistant’ patient
-No EPS
What are the negative symptoms associated with Clozapine
Risk of agranulocytosis
Lowers seizure threshold: Easier for seizures to occur
Weight gain
Only licenced for unresponsive patients
Properties of Risperidone
-Affinty:5-HT2 > D2
-Broad efficacy and more potent than Clozapine
-Little to No EPS, ANS and cardiac S/E at low doses
Properties of Aripiprazole
-A fairly new drug
-Partial agonist at D2
-limited S/E
-Long 1/2t for better compliance
What advantages does 2nd gen have over 1st gen
-Little or no EPS
-Treating positive and negative symptoms
-Treatment resistant patients
What are some non-psychiatric indications for antipsychotics
Anti-emetics:
-In older agents
- Blocks Dopamine receptor centrally and peripherally in the stomach
Sedative
-Blocks H1 receptor (Promethazine)
What can Extra pyramidal reactions cause/ side effects
-Acute dystonia; Parkinsonian
>Early onset
>Reversible
-Tardive Dyskinesia: Repeated uncontrollable movement
>Late onset
>More serious
>Often irreversible
What are the effects of the Autonomic Nervous system effects
Anti-Muscarinic effects
>Loss of accommodation
>Dry mouth
>Difficulty urinating
>Constipation
Adreno-receptor blocking effects
>Orthostatic hypotension
>Impotence
What are metabolic and endocrine side effects
Weight gain
Hyperglycaemia secondary to insulin resistance
Hyperprolactic aemia
What are the cardiac side effects of anti-psychotics
-Thioridazine: Ventricular arrythmia, cardiac conduction block, sudden death
What are the toxic effects of Anti-psychotics
Agranulocytosis
Jaundice
Skin eruption
What are the Behavioural effects of Anti-psychotics
Older agents unpleasant to take
Pseudo depression
Toxic confusional state
What affects does smoking have on anti-psychotics
Increases the metabolism of the anti-psychotics
-Found in the cigarette not the Tobacco
Name some other classes of Anti-psychotics and their drugs.
Thioxanthenes: Flupentixol and Zuclopenthixol
Diphenylbutylpiperidines:
