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Phar 301 > Psychosis > Flashcards

Psychosis Flashcards

1
Q

What is Chlorpromazine? What does it do?

A

First typical antipsychotic
Similar to Reserpine
Blocks DA-1 and DA-2 receptors (incl. autoreceptors)
Strongly inhibits cAMP production from DA

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2
Q

What is haloperidol? What does it do?

A

A typical antipsychotic
Very weakly inhibits cAMP production from DA (equally as effective as eg CPZ)
Binds DA-2 preferrentially

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3
Q

What is clozapine? What does it do?

A

An atypical antipsychotic (in the clozet)
Little or no ACUTE EPS
Pros:
Works in more patients than classical neuroleptics
No EPS or prolactin surge
No tardive dyskinesia
Cons:
Severe, infrequent adverse effect on blood cells
Weight gain (diabetes?)
Risk of seizures
Therefore: not first line

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4
Q

What is Phencyclidine? What does it do?

A

PCP

NMDA glutamate receptor agonist

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5
Q

Define EPS

A

ExtraPyramidal Symptoms i.e. Parkinson-like Motor impairment

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6
Q

Define APD

A

Antipsychotic Drug

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7
Q

Define A neuroleptic

A

An antipsychotic that produces EPS, especially catalepsy

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8
Q

Define the mesolimbic dopamine pathway and what happens when its DA receptors are blocked

A

Ventral tegmental area to nucleus accumbens

Block postsynaptic DA receptors : inhibit psychosis

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9
Q

Define the nucleus accumbens

A

Main terminal area for mesolimbic DA pathway

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10
Q

Define Positron emission tomography

A

PET scan, allows to test for brain activity

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11
Q

Name 3 of the 7 positive symptoms of schizophrenia

A 
Delusions
hallucination
thought disorders
agitation
grandiosity
suspiciousness
hostility
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12
Q

Name 3 of the 5 negative symptoms of schizophrenia

A 
Blunted emotions (flattened affect)
Emotional and social withdrawal
Poor rapport
passive/apathetic
lack of spontaneity
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13
Q

Define the 2 cognitive symptoms of schizophrenia

A

Poor memory

Poor abstract thinking, etc

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14
Q

What causes schizophrenia?

A

We have no idea

high inheritability, twins have 50% chance of both having

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15
Q

What do MRI scans of Schizophrenic patients reveal?

A

Larger ventricle (less cortical matter)

Related somehow to DA

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16
Q

What do MRI scans of Schizophrenic patients reveal?

A

Larger ventricle (less cortical matter)

Related somehow to DA

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17
Q

True false? Neuroleptics keep the “crazy” at bay by locking it up and lot letting the patient express it

A

False

Not a chemical straightjacket, takes the crazy away

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18
Q

What is a common side effect of neuroleptics?

A

Parkinson’s-like symptoms

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19
Q

What are 4 problems with antipsychotic drugs?

A

Provide only symptomatic relief (doesn’t cure the crazy)
Need to be taken long term
Are often not taken (can forget due to cognitive deficiency)
Block DA receptors (leads ot dysphoria)

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20
Q

What are the two types of DA receptor and what does each one do to cAMP levels when activated?

A

D1 subtype increases cAMP

D2 subtype decreases cAMP

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21
Q

If drug A has a lower IC50 than Drug B, what can be implied about its potency?

A

drug A is more potent

22
Q

It was discovered that typical Neuroleptics have a suspiciously strong correlation between Average Daily dose and IC50 value for which type of DA receptor?

A

D2 receptor

correlation falls apart when you look at newer drugs

23
Q

What are the two subtypes of DA receptor and what does each one do to cAMP levels when activated?

A

D1-like subtype increases cAMP (D1 and D5)

D2-like subtype decreases cAMP (D2, D3, D4)

24
Q

It was discovered that typical Neuroleptics have a suspiciously strong correlation between Average Daily dose and IC50 value for which type of DA receptor?

A

D2 receptor

correlation falls apart when you look at newer drugs

25
Q

What are symptoms of Amphetamine induced psychosis?

A

Ideas of reference, paranoid delusions
ONLY POSITIVE SYMPTOMS
neuroleptics rapidly reverse symptoms
Schizophrenics are more on the edge for amphetamines

26
Q

What are some symptoms of PCP induced psychosis?

A

low doses mimic some positive and negative symptoms

27
Q

True/False? LSD can cause schizophrenia-like experiences

A

False

28
Q

What is the DA hypothesis of schizophrenia? What evidence is there for it (4) and what are its issues (3)?

A

Excess DA causes schizophrenia
Evidence:
Stimulant psychosis and reversal by DA receptor blockers
Antipsychotics block DA receptors
Increased Brain DA release during acute psychosis
DA receptor abnormalities?

Issues:
Therapeutic delay (unexplained)
Non-responders to antipsychotic drugs
Clozapine (low D2 receptor affinity but still neuroleptic)

29
Q

Where are D1-like receptors located?

A

Postsynaptically ONLY

30
Q

Where are D2-like receptors located?

A

Autoreceptors on dendrites
Autoreceptors on terminals
AND postynaptic receptors

31
Q

What is a typical symptom of atypical antipsychotics?

A

The inhibition of D2 receptors leads to increase of prolactin, which (can) lead to milk secretion

recall DA = “prolactin inhibitory hormone”

32
Q

True/False? Atypical neuroleptics produce Tardive Dyskinesia

A

False

33
Q

What kind of blockade do atypical antipsychotic administration cause?

A

Mesolimbic DA blockade

no Nigrostriatal blockade

34
Q

Is there a [Nigrostriatal, Mesolimbic] blockade when given [typical, atypical] antipsychotics?

A

Classical: NS inhib, ML inhib
Atypical: NS no, ML inhib

35
Q

Is there a [Nigrostriatal, Mesolimbic] blockade when given [typical, atypical] antipsychotics?

A

Classical: NS inhib, ML inhib
Atypical: NS no, ML inhib

36
Q

What receptor needs to be blocked to cause EPS? What level of blockade is required?

A

D2 receptors

EPS occurs at around 80% blockade

37
Q

Define Clozapine’s affinity for each DA terminal area

A

Equal

same for striatum as mesolimbic

38
Q

True/False? Clozapine provides good blockade aof D2 receptors at low concs

A

True

39
Q

True/False? Clozapine has a high affinity for D3 receptors

A

False

D3 antagonists are not effective antipsychotics

40
Q

D4 DA receptors have unusually high affinity for clozapine. Are selective D4 antagonists antipsychotic?

A

No

41
Q

True/False? Many antipsychotic drugs have high selectivity for DA receptors

A

False
Antipsychotics are promiscuous - they bind all over the place
Other targets include muscarinic and adrenergic receptors

42
Q

Compared to classical antipsychotics, atypicals block (more/fewer) D2 receptors, and block (more/fewer) 5HT2A receptors

A

Fewer D2 (less EPS)
More 5HT2A
NOT ALWAYS TRUE
but general rule

43
Q

What is the most promising theory for antipsychotics?

A

The Depolarization inactivation theory

Explains why antipsychotic drugs take a while to work as well as EPS vs no EPS

44
Q

What is the Depolarization inactivation theory?

A

Depolarization inactivation occurs selectively in mesolimbic system
CHRONIC action is what counts!
(recall nigrostriatal pathway is not blocked by atypicals)

45
Q

DA D2 agonists hyperpolarize DA cells by _____

A

Stimulating autoreceptors

Cells fire slower (or stop firing)

46
Q

True/False? DA cells have pacemaker activity

A

True

47
Q

DA D2 antagonists depolarize DA cells by _____

A

Blocking autoreceptors

When antagonist is given acutely, the DA cell fires Faster

48
Q

What happens to DA cells during CHRONIC Antagonist treatment?

A

DA cells may no longer be able to fire (Silent)
“Depolarization block”
Typical APDs do this to mesolimbic AND nigrostriatal cells
Atypical APDs do this to mesolimbic NOT nigrostriatal cells (reason not known)

49
Q

Acute APDs Increase cell firing in which pathways?

A

Nigrostriatal AND mesolimbic pathways

50
Q

How do atypical APDs, given chronically, preferentially inactivate MESOLIMBIC DA neurons?

A

¯_(ツ)_/¯

Phar 301 (23 decks)

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