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pharmacology > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

What are the + symptoms of schizophrenia and psychosis?

A

“Acting out”

  • Delusions
  • Agitation
  • Hallucinations
  • Disorganized thinking
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2
Q

+ symptoms are associated with…?

A

“Typical antipsychotics” and Mesolimbic

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3
Q

What are the - symptoms of schizophrenia and psychosis?

A

“Depressed mood”

  • Apathy
  • Social isolation
  • Poor speech
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4
Q
  • symptoms are associated with…?
A

“Atypical antipsychotics” and Mesocortical

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5
Q

What is the dopamine (DA) hypothesis?

A

DA hypothesis says that excess DA in causes schizophrenic and psychotic behaviors.

Homovanillic acid is a metabolite of DA. There is an increased amount of urinary homovanillic acid in psychotic/schizophrenic patients.

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6
Q

What kind of drugs induce psychotic behavior?

A

Drugs that ↑ DA (AMANTADINE) and drugs that inhibit the reuptake of DA (AMPHETAMINE)

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7
Q

Mesolimbic pathway responsible for?

A
  • Arousal
  • Memory
  • Behavior
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8
Q

Nigrostriatal pathway responsible for?

A
  • Modulation of EPS
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9
Q

Tuberoinfundibular pathway responsible for?

A
  • Regulation of prolactin
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10
Q

Mesocortical pathway responsible for?

A
  • Cognition

* Socialization

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11
Q

MOA of Typical antipsychotics?

A

D2 receptor antagonists; blocks D2&raquo_space;> 5-HT2

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12
Q

Blockade of D2 in mesocortical pathway leads to…?

A

Worsens the - symptoms

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13
Q

Blockade of D2 in the nigrostriatal pathway leads to…?

A

EPS, Parkinsonism

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14
Q

Blockade of D2 in the tuberoinfundibular pathway leads to…?

A

Prolactin release (Ex: men might have gynecomastia; milk discharge even when not pregnant)

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15
Q

When to use typical antipsychotics?

A
  • Schizophrenia (Haloperidol)
  • Drug-induced psychosis
  • Tourette’s (haloperidol, pimozide)
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16
Q

What are the typical antipsychotics?

A
  • Chlorpromazine (low potency)
  • Fluphenazine (high potency)
  • Haloperidol (high potency)
  • Thioridazine
  • Loxapine
  • Trifluoperazine
  • Thiothixene
  • Pimozide (Tourette’s)

High potency = very strong antagonist of the D2 receptor. Most D2 blockade.

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17
Q

What are the typical antipsychotic toxicities?

A
  • M, H1, alpha1 blockade
  • EPS (dystonia, pseudoparkinsonism) - Treat with anticholinergics
  • Akathisia - treat with Propranolol
  • Menstrual irregularities, prolactin release
  • Tardive dyskinesia
  • Neuroleptic malignant syndrome (NMS)
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18
Q

Blockade of Muscarinic (M) receptor cause…?

A
  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention (pt. has problem with urination)
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19
Q

Blockade of H1 receptor causes…?

A

Sedation

20
Q

Blockade of alpha1 receptor causes…?

A

Orthostatic hypotension

21
Q

Tardive Dyskinesia

A

IRREVERSIBLE

Happens months - yrs. later

Tongue protrusion, lip smacking, abnormal movements, “Rabbit syndrome”

22
Q

Neuroleptic malignant syndrome (NMS)

A

Different from Serotonin syndrome b/c occurs WEEKS - MONTHS later. No GI effect.

  • Muscle rigidity, loss of consciousness, tachycardia, high fever, ↑ creatine kinase (b/c of muscle injury due to prolonged contraction), diaphoresis
  • Decreased reflexes
  • Normal Pupils
23
Q

Which drug is used to treat NMS?

A

Dantrolene = a muscle relaxant

24
Q

How does Dantrolene (for NMS) work?

A

Binds to ryanodine receptors and prevents Ca2+ release from the sarcoplasm ⤑ inhibits muscle contractions

25
Q

Toxicity of chlorpromazine and thioridazine?

A

Both have the MOST muscarinic, histamine, and alpha1 blockade.

Both are LOW potency.

26
Q

Toxicity of thioridazine?

A

~ Highest QT interval increase * Pigment retinopathy.

Frequent eye exam is needed

27
Q

Toxicity of chlorpromazine?

A

Corneal deposits

Frequent eye exam is needed

28
Q

What drugs can be used to treat dystonia and Parkinsonism?

A

Anticholinergics like Benztropine and diphenhydramine

29
Q

How does LSD mimic schizophreia?

A

By stimulating 5-HT2a receptor

30
Q

Serotonin inhibits DA release in the nigrostriatal pathway. This causes…

A

⇣EPS

31
Q

5-HT2a block in tuberoinfundibular pathway…

A

⇣ release of Prolactin

32
Q

In the Mesolimbic pathway, blocking 5-HT2a…

A

Does not increase DA levels

33
Q

In the Mesocortical pathway, blocking 5-HT2a…

A

Increases DA ⤏ improves the - symptoms

34
Q

Atypical antipsychotics target which neurotransmitter?

A

Serotonin.

5-HT2&raquo_space;> D2;
Some D3 and D4 blocks

35
Q

MOA of Atypical antipsychotics?

A

⇡ DA release to relieve negative (-) and some positive (+) symptoms of psychosis

  • All Atypical antipsychotics prolong QT interval
36
Q

What are the Atypical antipsychotics?

A
  • Aripiprazole
  • Olanzapine
  • Quetiapine
  • Risperidone
  • Ziprasidone
  • Clozapine
37
Q

Aripiprazole

A
  • Partial D2 and 5-HT1a agonist
  • 5-HT2a antagonist
  • used for: bipolar disease, irritability in autism
  • In the mesolimbic pathway: ⇣DA
  • In the mesocortical pathway: ⇡ DA
38
Q

Clozapine

A

alpha1 = D4 > 5-HT2a > D2 = D1

*Can cause orthostatic hypotension since alpha1 blockade is stronger

Causes: Night time “drooling” (paradox)

Weight gain (b/c of block of 5-HT 2c?)

Causes agranulocytosis. Hence, weekly blood count for the 1st 6 months of treatment, then every 3 weeks thereafter

39
Q

Locaserin is used for…

A

Weight loss.

Agonist of 5-HT2c

40
Q

Olanzapine

A
  • Less ANS effects
  • Blocks D3, D4
  • Fewer EPS
  • Weight Gain
  • Sedation

~ Can use in combo with fluoxetine for mania ~

5-HT2a > H1 > D4…

41
Q

Quetiapine

A
  • D2 blocker, but binds for a short time
  • H1 > alpha1 > M1,3…
  • most sedation
  • Minimal muscarinic blocks,
42
Q

Risperidone and Paliperidone

A
  • alpha1 blockade ⤑ hypotension.
  • Increased prolactin, hyperlipidemia, hyperglycemia

Paliperidone is an active metabolite of risperidone (24 hr. dosing)

43
Q

Ziprasidone

A
  • Blocks 5-HT nd NE reuptake

* Skin rxn, eosinophilia

44
Q

Adverse effects of 1st generation anti-psychotics?

A

Neurologic side effects

45
Q

Adverse effects of 2nd generation anti-psychotics?

A

Metabolic side effects

46
Q

What does the glutamate hypothesis say?

A
  • PCP and ketamine cause psychosis and block NMDA receptor

* NMDA receptor found on GABA neurons, increases GABA release

pharmacology (3 decks)

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