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IC Part 2 > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

Antipsychotics

A

Primarily used in treatment of schizophrenia but used for any disorder involving psychotic symptoms

  • major tranquilizer is the original name (barbs and benzos minor tranquilizers) - antipsychotic effects were discovered when major tranquilizers were used to quiet institutionalized mental pts
  • called neuroleptics- based on tendency to produce neurological side effects
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2
Q

Schizophrenia positive symptoms

A

hallucinations (auditory), delusions (inappropriate beliefs), disorganized

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3
Q

Schizophrenia negative symptoms

A

flat or inappropriate effect, social isolation or withdrawal, alogia (poverty of speech), avolition, anhedonia, cognitive deficits

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4
Q

Pathogenesis of schizophrenia

A
  • neurodevelopmental
  • 50% heritability
  • likely involves aberrant dopaminergic, glutamatergic, and/or serotonergic activity
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5
Q

Dopamine neurochemical hypothesis

A
  • positive symptoms arise from hyperactivity of CNS dopamine systems- mesolimbic and mesocortical (from ventral tegmental area to cortical and limbic areas)
  • thought to be because L-DOPA can cause psychosis (too much dopamine), amphetamine (releases and blocks reuptake of dopamine) can cause psychosis and makes schizophrenics worse
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6
Q

Serotonin hypothesis

A

5-HT2a and 5-HT2c receptors mediate hallucinogenic effects

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7
Q

Glutamate

A

-phencyclidine and ketamine produce effects that resemble aspects of schizophrenia and exacerbate symptoms in schizophrenics

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8
Q

Mechanism of action of antipsychotics

A

true mechanism is unknown

  • all are D2 dopamine receptor antagonists
  • serotonin receptors and/or novel D2 like receptors (D3 or D4) may be involved
  • also interact with other receptors (a1. Ach, histamine, etc) which contributes to side effects and varies with each drug- dirty drugs
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9
Q

Pharmacological effects of antipsychotics

A

initial- sedation, decreased agitation

In schizophrenics- positive symptoms improve over weeks to months of treatment (problem with dopamine hypothesis because of compensatory changes leading to upregulation of dopamine receptors lead to antipsychotic effects)

Negative symptoms- improved by newer drugs, but older typical drugs have little effect

In normal persons- dysphoria, disinterest, blunted affect

Antiemetic- blockage of dopamine receptors in CTZ, not useful for motion sickness

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10
Q

Early side effects

A

Neurological- extrapyramidal effects (EPS)- can cause dystonia (1-5 days), akathisia (5-60 days),

parkinsonian symptoms (tremor, rigidity, bradykinesia; 5-30 days) due to blockage of striatal dopamine receptors –can be treated with anticholinergics

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11
Q

More side effects

A

increased prolactin release due to blockade of D2 receptors- amenorrhea, gynecomastia, galactorrhea (dopamine inhibits prolactin release)

Weight gain, metabolic syndrome, diabetes

anti-histaminergic effects- sedation
orthostatic hypotension and sexual dysfunction- alpha adrenergic

anticholinergic effects (dry mouth)

CV alterations- prolonged QT

Blurred vision, retinitis pigmentosa (thioridazine)

neuroleptic malignant syndrome- treated with dantrolene- malignant hyperthermia due to impaired muscle activity and sweating

decreased seizure threshold

poikilothermy- can lead to hypothermia

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12
Q

long term side effects

A

tardive dyskinesia- abnormal movements and facial disfigurement, frequently irreversible
-may be due to long term dopaminergic receptor blockade

perioral tremor (rabbit syndrome)

blood dyscrasias- agranulocytosis can occur with clozapine and some phenothiazines

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13
Q

What drug causes agranulocytosis

A

clozapine

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14
Q

pharmacokinetics

A

IM, IV, PO

Highly lipophilic so can get into brain

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15
Q

Drug interactions

A

potentiate CNS depressants- barbiturates

  • block dopamine agonists
  • modify cv drugs
  • inc risk of seizures with other drugs
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16
Q

Typical antipsychotics

A
  • Effective against positive, but not negative symptoms
  • Produce EPS and tardive dyskinesia
  • all are D2 antagonists and are antagonists at variety of other receptors- confers unique SE
17
Q

Phenothiazines

A

typical antipsychotics
Chlorpromazine- first antpsychotic
Fluphenazine
Thioridazine

18
Q

Haloperidol

A

typical antipsychotic

most widely prescribed antipsychotics
relatively more selective for dopamine receptors- highest incidence of EPS

also used for tourettes, huntingtons

19
Q

Thiothixene

A

Other structure of typical antipsychotic

20
Q

Atypical antipsychotic

A
  • No EPS or tardive dyskinesia, antagonist at 5HT2 receptors
  • Clozapine- 5HT2>D2
  • activity at lots of receptors
  • some effect on negative symptoms as well as positive symptoms

agranulocytosis in abt 3% of pts

approved ONLY for treatment resistant pts who must receive regular blood tests

21
Q

Newer antipsychotic

A
  • trying to achieve atypical profile
  • significant 5-HT2 antagonist activity
  • generally improved side effects because of fewer extraneous receptor interactions
22
Q

Resperidone

A
  • newer antipsychotic
  • 5HT2=D2
  • EPS at higher doses, does not effect negative symptoms
23
Q

Lurasidone

A

5HT2, D2, 5HT7
-newer antipsychotic
less incidence of EPS

also used for depression in bipolar disorder

24
Q

Olanzepine

A 
newer 
even less EPS 
5HT2> D2
high incidence of weight gain and metabolic syndrome
may improve negative symptoms
25
Q

Quetiapine

A

newer antipsychotic
5Ht2=D2
high incidence of weight gain and metabolic syndrome
may improve negative symptoms

26
Q

Ziprasidone

A

newer antipsychotic
D2, 5-HT2A, 5-HT1d antagonist
5-HT1a agonist

27
Q

Aripiprazole

A

D2, 5HT1a partial agonist
5-HT2A antagonist
partial agonism at D2 receptors may allow for sufficient stimulation to prevent EPS while preventing over stimulation

used for refractory depression

28
Q

Other uses of antipsychotics

A

management of agitation and psychotic symptoms in acute mania and bipolar disorder, delirium, depentia, alcoholic hallucinosis (during heavy drinking, not withdrawal because of inc risk of seizures)
-maintenance of bipolar disorder
dopamine agonist induced psychotic symtpoms- parkinson’s

tourettes, huntingtons, refractory depression, depression in bipolar disease

IC Part 2 (27 decks)

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