Antipsychotic drugs Flashcards

0
Q

What are the two main classes of drugs?

A

1) Typical: D2 receptor antagonists but with multiple sites of action
eg. phenothiazines, butyrophenones, cholorpromazine, haloperidol

2) Atypical: serotonin and D2 antagonists
e. g. clozapine, risperidone, aripriprazole

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1
Q

What are the antipsychotic drugs?

A
  • used to control behavioural disorders such as schizophrenia
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2
Q

What are the distinction between typical and atypical antipsychotic drugs?

A
  • not well defined but mainly based on receptor profile, incidence of extrapyramidal side effects (less in the atypical group)
  • efficacy against negative symptoms

*other sites of actions may include Alpha1, mAChR, Histamine receptor and other serotonin receptors

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3
Q

What are the symptoms shown from a schizoprenia patient?

A

1) Positive symptoms: delusions, hallucinations, disorganised thoughts and abnormal behaviours
2) Negative symptoms: blunted emotions, poverty of speech, attention impairment, loss of motivation
3) Mood Symptoms: depression, anxiety, impulse control
4) Cognition: memory, executive functions

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4
Q

What are the causes for schizophrenia?

A
  • not well understood: both environmental and genetic factors
  • pregnancy complication: flu? deliver? gestational diabetes?
  • stress
  • drugs
  • disease of hypoglutamatergic or hyperdopaminergic altering input to the cortex
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5
Q

Theory purposed that dopamine might have been the cause leads to schizophrenia

A
  • A disease of hyperdopaminergic dysfuction

- positive correlation seen between D2 receptor blockade and antipsychotic efficacy

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6
Q

Theory purposed that glutamate might have been the cause leads to schizophrenia

A
  • disease of hypoglutamatergic dysfunction
  • NMDA antagonists produce psychotic symptoms
  • reduced glutamate and glutamate receptor densities found in schizophrenic patients
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7
Q

Theory purposed that 5-HT- DA might have been the cause leads to schizophrenia

A
  • 5-HT2A has important influences on DA pathways
  • Atypical antipsychotic drug target serotonin and DA systems= better treatment and side effect profile

-inputs from Raphe (i.e. 5-HT) to dopaminergic cell bodies and terminals

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8
Q

What are the old treatments for schizophrenia?

A
  • insulin induced coma therapy, prefrontal lobotomy, electroconvulsive shock therapy
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9
Q

The main categories of drugs for schizophrenia.

A
  • first generation (typical): chloropromazine, haloperidol, fluphenazine, flupenthixol, clopenthixol
  • second generation (atypical): clozapine, risperidone, sertindole, quetiapine, amisulpride, aripiprazole, zotepine
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10
Q

Atypical antipsychotics (D2 and 5HT2 antagonism)

A
  • these are second generation of antipsychotics with improved efficacy and side effects
  • antagonise D2 and 5HT2 receptors
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11
Q

Effects of D2 receptor blockade drugs

A
  • mesolimbic: reduces positive symptoms
  • mesocortical: increases negative symptoms, cognitive deficits
  • nigrostriatal: induces motor side effects (parkinsonism)
  • tuberoinfundibular: effects on hormone secretion (hyperprolactinaemia)

= major side effects and high doses can acutely provide behavioural control e.g. haloperidol

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12
Q

Aripiprazole

A
  • partial agonist at D2 receptor and 5-HT2A antagonist
  • no mACh receptor efficacy, 5-HT1A and 5-HT2C partial agonists
  • moderate affinity for 5-HT transporter, histamine and alpha adrenergic receptors

= partial agonists mean will antagonise D2 receptors when there’s excessive activation (mesolimbic DA hyperactivity); agonise D2 receptors where dopamine is low (mesocortical DA hypoactivity) and prevent total blockade of D2 receptors so conserve some nigrostriatal functionsk

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13
Q

Side Effects from receptor blockade

A
  • D2: prolactin elevation
  • M1: anti-muscarinic effects
  • H1: sedation, weight gain, dizziness
  • alpha 1: hypotension
  • 5-HT2C: satiety blockade
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14
Q

What are the extra-pyramidal disturbances of the drugs? (blockade of DA2 receptors in nigrostriatal pathway)

A
  • parkinsonian
  • acute dystonia
  • akathisia
  • tardive dyskinesia

= incidence can be reduced with atypical drugs

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15
Q

What is the pharmacokinetics of the schizophrenic drugs?

A
  • absorbed from blood (oral administration)
  • variability in peak plasam conc due to varied tissue binding
  • 90% plasma protein bound
  • 15 to 30 hours half life
  • rapid dissociation makes atypicals less able to achieve total blockade
  • often admin as slow release depot
16
Q

What is the clinical efficacy for these drugs?

A
  • 30% of patients fail to respond
  • little difference in efficacy between drugs on positive symptoms
  • typical drugs are ineffecive at relieving negative symptoms
  • atypical drugs= 1st line treatment: RISPERIDONE, QUETIAPINE, ZOTEPINE
  • 2nd line: CLOZAPINE (risk of agranulocytosis)
17
Q

What is the clinical efficacy for antipsychotics drugs?

A
  • 30% of patients fail to respond
  • little difference in efficacy between drugs on positive symptoms
  • typical drugs ineffective at relieving negative symptoms
18
Q

What is the 1st line treatment for atypical drugs?

A
  • Risperidone, quetiapine, zotepine
19
Q

What is the 2nd line treatment of drugs?

A
  • Clozapine

* there is a risk of agranulocytosis

20
Q

When would haloperiodol be used?

A
  • in severe psychotic patients
21
Q

What are the side effects from typical drugs?

A
  • muscarinic side effects
22
Q

What are the side effects of atypical drugs?

A
  • weight gain, insomnia, sedation
23
Q

What are the anti-psychotics with multiple therapeutic mechanisms?

A
  • improved efficacy

- eg risperidone, quetiapine, olanzapine, clozapine

24
Q

What are the anti-psychotics with single selective mechanisms?

A
  • a bit of side effects

- eg Haloperidol

25
Q

What are the anti-psychotics with multiple mechanisms?

A
  • lots of side effects

- eg chlorpromazine