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Antipsychotics > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

Positive symptoms of schizophrenia

A
  • active auditory hallucinations
  • paranoia
  • delusions
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2
Q

Negative symptoms of schizophrenia

A
  • depressive-like symptoms
  • flat affect
  • withdrawn
  • amotivational
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3
Q

Dopamine hypothesis of schizophrenia

A

(1963) psychoses are the result of excessive dopamine activity in CNS; based in the observations that:
(1) dopamine antagonists alleviate psychosis
(2) sympathomimetics which cause dopamine release can induce psychosis

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4
Q

General characteristics of all antipsychotics

A
  • orally administered (IM may be an additional option for some to be used in cases of acute exacerbation)
  • extensive first-pass hepatic metabolism
  • extensively plasma protein bound 95-98%; therefore very high potential for drug interactions with other plasma bound drugs
  • generally long to very long half life (ex. chlorpromazine = 30 hrs)
  • 70% of patients respond well to these drugs
  • 1st generation antipsychotics all have anti-emetic effect (ex: promethazine, compazine)
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5
Q

“B-52” combination drug therapy

A
  • haloperidol, lorazepam, diphenhydramine
  • sometimes given IM for acute psychosis
  • produces an acute neuroleptic syndrome of effects
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6
Q

neuroleptic syndrome

A
  • sedation
  • emotional quieting
  • psychomotor slowing
  • affective indifference / flat affect
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7
Q

neuroleptic malignant syndrome

A
  • results from decreased dopamine activity
  • pt’s nervous system becomes supersentitized to dopamine, this effect may not be reversible
  • muscular rigidity, difficulty breathing/diaphragm rigidity, autonomic hyperactivity, high fever
  • treatment is dilantin
  • only occurs in 1% of pts taking antipsychotics, but among those affected 20-30% fatality
  • unpredictable: may occur with therapeutic dosing; can happen with first dose or after chronic use
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8
Q

tardive dyskinesia

A
  • an IRREVERSIBLE complication of LONG TERM use of dopamine antagonist therapy
  • system becomes supersensitized to dopamine
  • uncontrollable motor problems: facial fasciculations, lip smacking
  • effects are opposite to parkinson’s; in parkinson’s pts have trouble moving, with t.d. pts have trouble not moving
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9
Q

Common side-effects of antipsychotics (list of 9)

A
  • akathisias / nervous energy (common reason for noncompliance)
  • dystonias (disorders of muscle tone)
  • dyskinesias (disorders of muscle movement); includes tardive dyskinesia
  • akinesia (absence of movement)
  • drug induced parkinsonism
  • neuroleptic malignant syndrome
  • blood disorders in general (agranulocytosis with clozapine)
  • endocrine: increased prolactin
  • cardiovascular: orthostatic hypotension, similar effects to quinidine (class 1a anti-arrythmic, blocks Na channels, slows action potential, prolonged QT)
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10
Q

Effect of dopamine on prolactin

A
  • dopamine normally inhibits prolactin

- dopamine antagonists increase prolactin levels (leads to a/dysmenorrhea and gynecomastia)

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11
Q

Common drug interactions with antipsychotics (list of 4)

A
  • potentiation with CNS depressants
  • interaction with OTC antihistamines (2nd generation antipsychotics have antihistamine effect; together produce synergistic sedation, slowed metabolism, increased appetite, and weight gain)
  • caution with anti-emetics (some anti-emetics are 1st gen antipsychotics)
  • interaction with other drugs that are highly plasma protein bound
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12
Q

1st generation antipsychotics

A

“typical” antipsychotics
- better for positive symptoms of schizophrenia, may exacerbate negative symptoms

MOA: dopamine type D2 receptor antagonists

3 classes: 
[NOTE: classes included for organizational purposes only, do not *need* to know for test]
- phenothiazines
- butyrophenones (haldol)
- thioxanthenes

contraindications: blood dyscrasias, parkinsonism, chronic alcoholism, liver disease

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13
Q

Phenothiazines

A
  • class of 1st gen antipsychotics
  • structurally similar to tricyclic antidepressants; share many characteristics
  • MOA: predominantly dopamine D2 antagonists, but also block alpha1, muscarinic, histamine receptors as well
  • less D2 selectivity means greater alpha1 and muscarinic affinity (less motor/extrapyramidal effects, more autonomic effects)
  • higher D2 selectivity means less alpha1/muscarinic affinity (more motor/extrapyramidal effects, less autonomic effects)
  • low D2 selectivity phenothiazines
  • moderate D2 selectivity phenothiazines
  • high D2 selectivity phenothiazines
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14
Q

Low dopamine type 2 selectivity phenothiazines (list of 3)

A
  • most autonomic effects among phenothiazines
  • least extrapyramidal effects among phenothiazines
  • chlorpromazine
  • promazine (least effective)
  • trifluopromazine
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15
Q

Moderate dopamine type 2 selectivity phenothiazines (list of 2)

A
  • mesoridazine
  • thioridazine
  • seldom used, black box warning in usa, quinidine-like effect on heart
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16
Q

High dopamine type 2 selectivity phenothiazines (list of 3)

A
  • least autonomic effects among phenothiazines
  • most extrapyramidal effects among phenothiazines
  • fluphenazine (decanoate formulation available/ very long acting ~2 months)
  • perphenazine
  • trifluoperazine
17
Q

Haloperidol

A
  • high to intermediate D2 selectivity

- decanoate formulation available

18
Q

Thioxanthenes (list of 2)

A

chlorprothixene
thiothixene

  • potent D2 receptor antagonists
  • commonly used
19
Q

2nd generation antipsychotics

A

“atypical” antipsychotics

  • only weakly antidopaminergic
  • 1st choice drugs for schizophrenia
    • treat both positive and negative symptoms
  • bc less effect on dopamine, less risk for tardive dyskinesia, neuroleptic malignant syndrome, and extrapyramidal effects

3 classes:

  • heterocyclic antipsychotics
  • serotonin 5HT-2A receptor antagonists
  • partial dopamine receptor agonists
20
Q

Heterocyclic antipsychotics (list of 6)

A
  • clozapine: associated with impaired clotting and agranulocytosis; requires regular scheduled blood draws to assess drug level and granulocytes/wbc’s
  • olanzapine: some incidents of sleepwalking; commonly given with a mood stabilizer for bipolar depression
  • loxapine
  • molindone
  • pimozide: also indicated for tourette’s
  • quetiapine: widely used, assoc with weight gain
21
Q

5HT-2A receptor antagonists (list of 3)

A
  • effective for controlling hallucinations, particularly auditory
  • 5HT-2A agonists produce hallucinations (psychedelics i.e.. LSD, psilocybin etc)
  • at higher doses can have haloperidol-like effects
  • risperidone
  • paliperidone: metabolite of risperidone; thought to antagonize 5HT-2A and D2 receptors
  • ziprasidone
22
Q

partial dopamine receptor agonists

A
  • aripiprazole *

MOA: a partial agonist in the presence of a full agonist (excess dopamine) is an antagonist! so blocks enough excess dopamine to reduce psychosis but bc is a partial agonist reduces risk of extrapyramidal effects and neuroleptic malignant syndrome

  • often used as an adjunct with another 2nd generation antipsychotic
  • sometimes used as an adjunct for monopolar depression (unclear MOA and effectiveness in this context)

Antipsychotics (1 decks)

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