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LCRS 1 - Pharmacology > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

What are the principle neurotransmitter defects in schizophrenia?

A

Increased DA in mesolimbic pathway: positive symptoms –> hallucinations (mediated by D2Rs)

Reduced DA in mesocortical pathway: negative symptoms –> affective flattening (mediated by D1Rs)

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2
Q

How are drugs targeting the dopaminergic system utilised in treatment of schizophrenia?

A
  1. Chlorpromazine: possible D2R antagonist
  2. Haloperidol: potent D2R antagonist
  3. Clozapine: 5-HT2A R antagonist
  4. Risperidone: 5-HT2A R + D2R antagonist
  5. Quetiapine: H1R antagonist
  6. Aripiprazole: partial D2R + 5-HT1A agonist
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3
Q

Which symptoms do anti-psychotics treat?

A
  • Only positive symptoms
  • Bc they are D2 antagonists correcting over activity of dopamine in mesolimbic system and striatum but have no effect on the forebrain dopamine deficits where negative symptoms are produced
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4
Q

What are the side effects of chlorpromazine?

A
  • Anti-cholinergic: sedation (common)

- Extra-pyramidal (less common)

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5
Q

What are the symptoms of schizophrenia?

A

Positive:

  • Delusions - paranoia
  • Hallucinations (auditory + visual)
  • Thought disorder - denial about oneself

Negative:

  • Avolition/apathy - loss of motivation
  • Alogia - lack of speech
  • Affective flattening - lack of emotion
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6
Q

What cause the negative symptoms of schizophrenia?

A

Decreased mesocortical dopaminergic activity

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7
Q

What are the 1st generation anti-psychotics and how do they work?

A
  1. Chlorpromazine - possibly D2R antagonism

2. Haloperidol - potent D2R antagonism

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8
Q

Is chlorpromazine or haloperidol more potent?

A

Haloperidol is a 50x more potent D2R antagonist

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9
Q

What are the 2nd generation anti-psychotics and how do they work?

A
  1. Clozapine - potent 5-HT2A R antagonist
  2. Risperidone - potent 5-HT2AR + D2R antagonist
  3. Quetiapine - potent H1R antagonist
  4. Aripiprazole - partial D2R + 5-HT1A R agonist
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10
Q

Which symptoms does clozapine treat?

A 
Positive symptoms (like most anti-psychotics)
Some negative symptoms - only drug that does this
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11
Q

Which is the most effective anti-psychotic?

A

Clozapine

Treats positive and SOME NEGATIVE symptoms

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12
Q

What are the side effects of clozapine?

A
  • Potentially fatal neutropenia, agranulocytosis, myocarditis
  • Weight gain
  • Tf only given in drug-resistant schizophrenia
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13
Q

What are the side effects of risperidone?

A
  • Weight gain
  • EPS
  • Hyperprolactinaemia
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14
Q

What are the side effects of quetiapine?

A
  • EPS (but lower incidence than other anti-psychotics)
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15
Q

What are the side effects of aripiprazole?

A
  • Weight gain
  • Hyperprolactinaeima
  • But both less than other anti-psychotics
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16
Q

How does aripiprazole work?

A

Partial agonist of D2 + 5-HT1A Rs

  • Brings down too much activity (mesolimbic)
  • Brings up too little activity (mesocortical)
17
Q

Why do some anti-psychotics cause extra-pyramidal symptoms?

A

Blockade of dopamine receptors in the nigrostriatal system can induce “Parkinson” like side effects

18
Q

What are the general side effects of anti-psychotics?

A
  • Anti-emetic effects
  • Anti-histamine effects
  • Extra pyramidal motor disturbances: acute dyskinesias, tardive dyskinesias (20-30%)
  • Endocrine effects: hyperprolactinaemia
  • Anti-muscarinic effects
19
Q

When do acute dyskinesias develop? How can they be reversed and controlled?

A
  • At the onset of treatment
  • Reversible with drug withdrawal
  • Controlled by anticholinergics or muscle relaxants e.g. diazepam
20
Q

What exacerbates tardive dykinesias? How are they overcome? When do they occur?

A
  • Worsened by drug withdrawal and anti-cholinergics
  • Irreversible
  • Overcome by increasing dose of anti-psychotic
  • Occur after several months or years of treatment
21
Q

What causes the endocrine effects associated with anti-psychotic treatment?

A

Blockade of dopamine receptors in the tuberofundibular pathway (from hypothalamus to median eminence + pituitary gland)

22
Q

What might cause tardive dykinesias?

A
  • Proliferation of dopamine receptors (pre-synaptic) in the striatum
  • Toxicity of anti-psychotics
23
Q

What are the typical anti-muscarinic side effects?

A

Blurring of vision, increased intra-ocular pressure, dry mouth, constipation, urinary retention

LCRS 1 - Pharmacology (33 decks)

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