Schizophrenia Flashcards by Fehintoluwa Bamgbade

\what is schizophrenia

Oscillation between normal and abnormal sense of reality and sense of reality

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What is Scz characterized by

Loss of contact with reality
Disruption of thought
-Perception
-Mood
-Movement

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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: This is when the prefrontal cortex usually develops.

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What are is the meaning of positive and negative symptoms

Positive: presence of symptoms that are not normally there
Negative: Absence of normal symptoms

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List some of the positive symptoms of SCZ

Delusions

Hallucinations

Disorganised speech

Grossly disorganized or catatonic behaviour

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List some negative symptoms of SCZ

Reduced expression of emotion

Poverty of speech

Difficulty in initiating goal-directed movements

Cognitive/Memory impairment

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What are the subtypes of SCZ

Paranoid schizophrenia: Delusion and hallucination
-thought disorder, disorganized behaviour, and mood flattening are absent
Disorganised: though disorder and mood flattening
Cationic: agitated, purposeless movement

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What are the causes of SCZ

Environmental factors

Genetics

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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

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What are the pathophysiological theories of Schizophrenia

1.Dopamine hypothesis

2.Glutamate hypothesis

3.GABA hypothesis

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What is the Dopamine hypothesis

That excess dopaminergic NTission in mesolimbic and striatal brain region results in schizophrenic symptoms

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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
Increase D receptor density
Successful treatment changed levels of homovanillic acid (dopamine metabolite)

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What the evidence against the dopamine hypothesis

Antipsychotic drugs only partially effective for most patients

NMDA receptor (glutamate receptor) antagonists (phencyclidine) more potent

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What is the glutamatergic hypothesis of schizophrenia

NMDA receptor antagonist are potent dopamine releasers
-This caused psychotic symptoms in a health human

The treatment of SCZ with D-serine, glycine and sarcosine (NMDA receptor modulators) have therapeutic benefits

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What is the GABAergic hypothesis of SCZ

Decrease in GABA leads to enhanced DA neuron activation there for more DA release

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what are the main targets of antipsychotic drugs

Dopamine receptor and serotonin receptor

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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

D5: increase cAMP in hippocampus and hypothalamus

How to D2 receptors work

Decrease cAMP in Gi-Coupled inhibition of adenylyl cyclase
-Inhibit Ca2+ channels: decrease neuronal activity
-Opens K+ channels

Increases motor activity and stereotypical behaviour in rats

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 two main classes of typical antipsychotics

-Phenothiazine class
-Butyrophenone class

How many groups of the class phenothiazide drugs are there and list some examples

Group 1: chlorpromazine; levomepromazine; promazine

Group 2: pericyazine; pipotiazine

Group 3:What are the drugs in group 2 phenothiazines

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

List some typical anti-psychotic drugs

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 Clonazpine

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 -Ziprasidone: Great risk of ECG effects

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