Schizophrenia and antipsychotics

Question 1

What is schizophrenia?

symptoms

Answer 1

A disorder of abnormal thought, perception, behaviour mood and attention. Chronic psychosis

Positive: Hallucinations (auditory) and delusions
Negative: lowered mood, withdrawal

Question 2

What dopamine system is typically impaired in schizophrenia?

Evidence?

Answer 2

Ventral tegmental area to the frontal cortex and limbic system (involved in emotions etc).
Overactive

Thus blocking dopamine receptors is what antipsychotics do

amphetamines increase dopamine release and cause schiz like symptoms. Blocked by ^

Question 3

What is the evidence for the role of glutamate in schizophrenia?

Answer 3

A decrease can lead to.

Phenylcyclidine (angel dust, PCP) models best psychosis symptoms. We know is blocks NMDA, so glutamate decrease.

So maybe increase of DA and decrease of Glutamate = schiz symptoms

Glycine agonists in trials improved negative symptoms

Question 4

Types of anti-psychotics and what each focuses on

Answer 4

1) typical: chlorpromazine (TC, dopamine antagonisy) and haloperidol. Mainly focus on positive symptoms.
2) Atypical: Clozapine. Affects posotve and negative

Nowadays: risperidone and olanzepine; apriprazole and quetiapine then clozapine

Question 5

Clozapine side effect

Answer 5

Can cause agranulocytosis, a decrease in circulating neutrophils

Question 6

All anti-psychotics are _____ antagonists?

where are these found

haloperidol and clozapine affinity

Answer 6

dopamine receptor. (D1-D5)

D1: in striatum, increase cAMP
D5: D1 like

D2: Gi so decrease in cAMP, striatum
D3: D2 like but in limbic system
D4: D2 like but in cortex and limbic

Haloperidol: D2 and D4
Clozapine: 10x for D4 than D2

Question 7

Why are haloperidol and chlorpromazine typical

Answer 7

They exhibit extrapyramidal effects such as parkinsonism. (EPS’s)

Question 8

Concept of up and down regulation

Answer 8

Upregulation: chronic use of an antagonist will cause an increase in the number of receptors
Down regulation: Chronic agonist use will cause there to be fewer receptors

E.g. with haloperidol chronically, increase of D2 in striatum and cortex but with clozapine, only cortex

Question 9

What are the two types of depression

Answer 9

1) unipolar where mood and apetite lowered, negative self concept. Endogenous (unknown) or reactive causes
2) Bipolar or manic depression, where mood fluctuates between depression and mania. Strong genetic basis.

NB Mania is heightened mood/ euphoria, irritability, poor insight

Question 10

What is the biochemical theory behind depression and what is the evidence?

problem?

Answer 10

Simple monoamine theory: depression is a result in a decrease in brain monoamines (serotonin, dopamine, noradrenaline)

Evidence: Reserpine depletes monoamines can cause depression; amphetamine.cocaine raise mood by blocking re uptake; AD’s increase brain monoamines by blocking re uptake or metabolism

AD’s increase monoamines immediately but therapeutic action occurs 2-6 weeks later. Potentially change in brain chem?

Question 11

How are monamines inactivated

Answer 11

• Reuptake

- Break down by MOA’s, MOAa for serotonina and noradrenaline, MOAb for dopamine. COMT also breaks down

Question 12

First generation antidepressant drugs

Answer 12

-Tricyclics: Amitryptyline, imipramime.
Block noradrenaline and serotonin reuptake. Can cause anti-muscarinic actions

-MAO inhibitors. Phenelzine. Irreversibly inhibits MAO’s

Question 13

Second generation antidepressant dugs

Answer 13

• Moclobemide- reversible MAOa inhibitor, acute increase in serotonin and noradrenaline
• Fluoxetine- SSRI, potent selective serotonin reuptake inhibitor

Question 14

What is the drug of choice for manic depression

Answer 14

Lithium carbonate. strangle no effect on unipolar depression. Overdose can cause seizure, tremor

-Also use of carbamazepine