schizophrenia

Question 1

what is schizophrenia (scz)

Answer 1

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

Question 2

What is Scz characterized by

Answer 2

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

Question 3

what is Epidemiology of Schizophrenia and what is it linked to?

Answer 3

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.

Question 4

What are is the meaning of positive and negative symptoms

Answer 4

Positive: presence of symptoms that are not normally there

Negative: Absence of normal symptoms

Question 5

List some of the negative symptoms of SCZ

Answer 5

Reduced expression of emotion

Poverty of speech

Difficulty in initiating goal-directed movements

Cognitive/Memory impairment

Question 6

What are the subtypes of SCZ

Answer 6

1.Paranoid schizophrenia

2. Disorganised

3.Cationic: agitated, purposeless movement

Question 7

what is Paranoid schizophrenia

Answer 7

Delusion and hallucination
-thought disorder, disorganized behaviour, and mood flattening are absent

Question 8

what is disorganised schizophrenia

Answer 8

thought disorder and mood flattening

Question 9

what is catatonic schizophrenia

Answer 9

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

Question 10

What are the causes of SCZ

Answer 10

Environmental factors

Genetics

Question 11

What are the environmental factors that can lead to SCZ

Answer 11

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

Question 12

What are the pathophysiological theories of Schizophrenia

Answer 12

1.Dopamine hypothesis

2.Glutamate hypothesis

3.GABA hypothesis

Question 13

What is the Dopamine hypothesis

Answer 13

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

Question 14

What is the evidence behind the dopamine theory

Answer 14

1. Most antipsychotics block D2 receptors
2. Drugs that increase dopaminergic activity aggravate or produce sycosis
3. 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)

Question 15

What the evidence against the dopamine hypothesis

Answer 15

Antipsychotic drugs only partially effective for most patients

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

Question 16

What is the glutamatergic hypothesis of schizophrenia

Answer 16

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

Question 17

What is the GABAergic hypothesis of SCZ

Answer 17

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

Question 18

what are the main targets of antipsychotic drugs

Answer 18

Dopamine receptor and serotonin receptor

Question 19

What are the positive symptoms of SCZ

Answer 19

Delusions
Hallucinations
Disorganised speech
Grossly disorganized or catatonic behaviour

Question 20

What is the brain regions and systems included in the dopamine hypothesis for schizophrenia

Answer 20

Substantial nigra

VTA

Tuberohypohyseal systems

Question 21

What is the proposed mechanism of the glutaminergic hypothesis

Answer 21

Hypofunction of NMDA receptors on GABAergic interneuron

Leads to less inhibition of principal glutaminergic cells

Activates dopamine expressing cells

More dopamine release

Question 22

What is the mechanism of the GABAergic synthesis

Answer 22

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

Question 23

which dopamine receptors does not have a role in psychosis

Answer 23

D1 receptos

Question 24

What are the main dopamine pathways

Answer 24

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

Question 25

What are the two families of dopamine receptors

Answer 25

D1-like: D1 and D5 D2-like: D2,D3 and D4 They are all metabotropic (G-protein)

Question 26

What are the mechanism of D1 and D5 receptors

Answer 26

D1: Increase cAMP by Gs-coupled of adenylyl cyclase expressed in the putamen, Nucleus Accumben, olfactory tubercle

Question 27

How to D2 receptors work

Answer 27

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

Question 28

What is difference between typical and Atypical anti-psychotics

Answer 28

-Receptor profile -Incidence of extra pyramidal side-effects -Efficacy in 'treatment-resistance' groups -Efficacy against negative symptoms

Question 29

What are the main classes of typical antipsychotics

Answer 29

-Phenothiazine class -Butyrophenone class

Question 30

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

Answer 30

Group 1: chlorpromazine; levomepromazine; promazine Group 2: pericyazine; pipotiazine Group 3: Fluphenazine and Prochlorperazine

Question 31

What are the side effects of the Phenothiazine groups

Answer 31

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

Question 32

What are the drugs in group 1 phenothiazines

Answer 32

chlorpromazine; levomepromazine; promazine

Question 33

What are the drugs in group 2 phenothiazines

Answer 33

pericyazine; pipotiazine

Question 34

What are the drugs in group 3 phenothiazines

Answer 34

fluphenazine; prochlorperazine

Question 35

What drug is under the class of Butyrophenone

Answer 35

Haloperidol Benperidol

Question 36

List some typical anti-psychotic drugs

Answer 36

Clozapine Risperidone Aripirazole

Question 37

Properties of Haloperidol

Answer 37

Use is limit due to severe (Extra pyramidal symptoms) EPS -High D2 receptor affinity -Potent -Has hypotensive side effects

Question 38

What are the positive properties of Clozapine

Answer 38

-Greater affinity to 5-HT than D2 -Potent D4 antagonist -Efficient in 'Treatment-resistant' patient -No EPS

Question 39

What are the negative symptoms associated with Clozapine

Answer 39

Risk of agranulocytosis Lowers seizure threshold: Easier for seizures to occur Weight gain Only licenced for unresponsive patients

Question 40

Properties of Risperidone

Answer 40

-Affinty:5-HT2 > D2 -Broad efficacy and more potent than Clozapine -Little to No EPS, ANS and cardiac S/E at low doses

Question 41

Properties of Aripiprazole

Answer 41

-A fairly new drug -Partial agonist at D2 -limited S/E -Long 1/2t for better compliance

Question 42

What advantages does 2nd gen have over 1st gen

Answer 42

-Little or no EPS -Treating positive and negative symptoms -Treatment resistant patients

Question 43

What are some non-psychiatric indications for antipsychotics

Answer 43

Anti-emetics: -In older agents - Blocks Dopamine receptor centrally and peripherally in the stomach Sedative -Blocks H1 receptor (Promethazine)

Question 44

What can Extra pyramidal reactions cause/ side effects

Answer 44

-Acute dystonia; Parkinsonian >Early onset >Reversible -Tardive Dyskinesia: Repeated uncontrollable movement >Late onset >More serious >Often irreversible

Question 45

What are the effects of the Autonomic Nervous system effects

Answer 45

Anti-Muscarinic effects >Loss of accommodation >Dry mouth >Difficulty urinating >Constipation Adreno-receptor blocking effects >Orthostatic hypotension >Impotence

Question 46

What are metabolic and endocrine side effects

Answer 46

Weight gain Hyperglycaemia secondary to insulin resistance Hyperprolactic aemia

Question 47

What are the cardiac side effects of anti-psychotics

Answer 47

-Thioridazine: Ventricular arrythmia, cardiac conduction block, sudden death

Question 48

What are the toxic effects of Anti-psychotics

Answer 48

Agranulocytosis Jaundice Skin eruption

Question 49

What are the Behavioural effects of Anti-psychotics

Answer 49

Older agents unpleasant to take Pseudo depression Toxic confusional state

Question 50

What affects does smoking have on anti-psychotics

Answer 50

Increases the metabolism of the anti-psychotics -Found in the cigarette not the Tobacco

Question 51

Name some other classes of Anti-psychotics and their drugs.

Answer 51

Thioxanthenes: Flupentixol and Zuclopenthixol Diphenylbutylpiperidines: