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Pharmacology > Antipsychotic Drugs > Flashcards

Antipsychotic Drugs Flashcards

1
Q

What tract is the source of psychosis?

A

Mesolimbic Tract

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2
Q

What is thought to be the cause of schizophrenia?

A

Too much DOPA activity

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3
Q

What about the medications used to treat schizophrenia supported the dopamine hypothesis?

A

The greater the D2 antagonistic binding affinity of a drug, the less of that drug that was needed to reach a therapeutic dose in schizophrenia.

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4
Q

What were the problems with the 1st generation treatments of schizophrenia?

A

They only treated the positive symptoms and a large proportion of patients did not respond to treatment.

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5
Q

What was the first antipsychotic medication?

A

Chlorpromazine

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6
Q

What is the main MOA of 1st generation antipsychotic drugs?

A

Blockage of D2 receptors in the mesolimbic tract

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7
Q

What other receptors can chlorpramazine (low potency antipsychotic) bind to that leads to other SE?

A
  • Muscarinic
  • Adrenergic
  • Histamine
  • Non-mesolimbic dopamine (nigrostriatal, tuberoinfundibular)
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8
Q

Chlorpromazine Ocular SE

A

Corneal deposits

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9
Q

Thioridazine Ocular SE

A

Retinal deposits

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10
Q

Chlorpramazine SE

A

DOPA - increased prolactin
M1 - blurred vision/urinary retention/dry mouth
α1 - orthostatic hypotension
H1 - sedation/weight gain

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11
Q

What is the cholinergic activity of the low potency antipsychotics like chlorpramazine?

A

Anti-cholinergic

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12
Q

What is the normal action of DOPA on ACh activity?

A

Inhibitory

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13
Q

What are the high potency antipsychotics?

A
  • Haloperidol

- Fluphenazine

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14
Q

What other receptors can haloperidol (high potency antipsychotic) bind to that leads to other SE?

A
  • Non-mesolimbic dopamine
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15
Q

Haloperidol SE

A
  • Parkinsonian-like effects
  • Akathesia
  • Tardive dyskinesia
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16
Q

What patients are at greater risk for acute/tardive dyskinesia on haloperidol?

A

Young males

17
Q

What are the classic tardive dyskinesia movements?

A

Oro-facial movements of blinking and tongue movements

18
Q

What are the SE that occur due to action of antipsychotics on the tuberoinfundibular tract?

A

Increased prolactin leads to galactorrhea with interruption of menstruation and osteopenia.

19
Q

What are the most important 1st generation antipsychotics?

A
  • Chlorpromazine
  • Thiothixene
  • Haloperidol
20
Q

What is the MOA of the 2nd generation antipsychotics?

A

5HT and DOPA dual antagonism blocking the dopamine and serotonin receptors

21
Q

How does serotonin antagonism reverse DOPA antagonism?

A

Serotonin normally acts on pre-synaptic DOPA neurons to inhibit the release of DOPA. Blockage of this receptor will cause the pouring out of DOPA from the presynaptic terminal.

22
Q

Risperidone SE

A
  • Exrapyramidal effects
  • Orthostatic hypotension
    NO M1 or H1 effects
23
Q

Ziprasidone SE

A
  • Extrapyramidal effects
  • Orthostatic hypotension
  • Sedation
24
Q

Quetiapine SE

A
  • Orthostatic hypotension
  • Anticholinergic effects
  • Sedation
25
Q

Olanzapine SE

A
  • Extrapyramidal effects
  • Orthostatic hypotension
  • Anticholinergic effects
  • Sedation
26
Q

Clozapine SE

A
  • Agranulocytosis
  • Myocarditis
  • Increased seizures
  • Orthostatic hypotension
  • Anticholinergic effects
  • Sedation
27
Q

What is a side effect that all of the 2nd generation antipsychotics have?

A

Metabolic syndrome - weight gain/glucose intolerance

28
Q

Aripiprazole MOA

A

Partial agonist of the D2 receptors that is unique because it will keep less than 80% of the D2 receptor blocked but also more than 65% by switching from agonist to antagonist

29
Q

What is a unique benefit of clozapine?

A

Decreases risk of suicide

30
Q

Neuroleptic Malignant Syndrome

A

DOPA systems goes haywire leading to fever, muscle rigidity and tremor and increased CPK

31
Q

What is the treatment for neuroleptic malignant syndrome?

A

Stop the DOPA blocker - use dantrolene as treatment but it’s still controversial

32
Q

What is a rare SE of antipsychotics in the elderly with dementia?

A

Rare increase in sudden death

33
Q

Which of the 2nd generation antipsychotic has the longest half life?

A

Aripiprazole - around 3 days

34
Q

What 2nd generation antipsychotic can increase the QT interval?

A

Ziprasidone

35
Q

What is a unique SE of lurasidone?

A

Akathesia

36
Q

What is the metabolite of risperidone?

A

Palliperidone

37
Q

What is an advantage of haloperidol over chlorpromazine?

A

Haloperidol does not have any of the muscarinic, adrenergic or histamine related side effects.

38
Q

Hit and Run Concept

A

Atypical drug-induced blockade of DA2 receptors is looser and not as long-lasting as with typical drugs. The blockade is present long enough to have the antipsychotic therapeutic effect but not long enough to cause side effects.

Pharmacology (74 decks)

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