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Pharmacology > Antipsychotic Drugs > Flashcards

Antipsychotic Drugs Flashcards

1
Q

Describe the dopamine hypothesis theory of Schizophrenia

A

Abnormality of brain fxn is due to OVERACTIVITY in brain DA pathways, esp. mesolimibic pathway

**Virtually all anti-psychotic drugs block D2 receptors

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2
Q

Drugs that increase dopaminergic activity that can aggravate or produce de novo schizophrenia

A
  1. Levodopa- Dopamine precursor

2. Cocaine-amphetamine- dopamine releaser

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3
Q

Most effective way to tx positive and negative sx

A

positive: D2 blockers on mesolimbic system

Negative: atypical antipsychotics (clozapine or olanzapine) via additional block of 5HT2A receptors on mesocortical pathway

**Use 5HT2A and D3 blockers to help + and - sx

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4
Q

What causes pseudoparkinson’s SE ( hypoactivity, bradykinesia, tremor)

A

loss of dopamine (via D2 blocking drugs) in the nigrostriatal pathway (basal ganglia)

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5
Q

EPS symptoms caused by anti-psychotics are due to DA in what pathways

A
  1. pseudoparkinson’s SE ( hypoactivity, bradykinesia, tremor)
    * * decrease DA in nigrostriatal pathway
  2. Hyperprolactinemia
  3. Poikilothermia
  4. Weight gain
    * *2-4: decrease of DA in tuberoinfundibular pathway
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6
Q

Which statement about the pathophysiologic basis of schizophrenia is most accurate?
A.  All clinically effective antipsychotic drugs have high affinity for dopamine D2 receptors
B.  Dopamine receptor-blocking drugs are used to alleviate psychotic symptoms in parkinsonism
C.  Drug-induced psychosis can occur without activation of brain dopamine receptors
D.  Serotonin receptors are present at lower than normal levels in brains of untreated schizophrenic patients
E.  The clinical potency of olanzapine correlates well with its dopamine receptor-blocking activity

A

C.  Drug-induced psychosis can occur without activation of brain dopamine receptors

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7
Q

Positive symptoms of schizophrenia (delusions, hallucinations) are believed to result from:
A.  Underactivity of norepinephrine neurons in the cortex
B.  Overactivity of dopamine neurons in the mesolimbic system
C.  Underactivity of serotonin neurons in the cortex
D.  Underactivity of dopamine neurons in the nigrostriatal pathway
E.  Overactivity of cholinergic neurons in the cortex
F.   Underactivity of glutamate neurons in the prefrontal cortex

A

B.  Overactivity of dopamine neurons in the mesolimbic system

F.   Underactivity of glutamate neurons in the prefrontal cortex
(causes hyperactivity in mesolimbic pathway= + sx and
causes hypoactivitiy in mesocortical pathway= - sx)

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8
Q

What are examples of 2nd generation Atypical antipsychotics

A
  1. Aripiprazole (Abilify)
  2. Risperidone (Risperdal)
  3. Olanzapine (Zyprexa)
  4. Clozapine (Clozaril)
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9
Q

What are examples of 1st generation Typical antipsychotics

A
  1. Haloperidol (Haldol)
  2. Chlorpromazine (Thorazine)

(“-azine” + Haldol)

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10
Q

How does serotonin (5HT2) cause schizophrenia symptoms?

A
  1. Activation of 5HT2A receptors on DA neurons in PFC–> decrease DA release= neg. sx
  2. Activation of 5HT2a receptors on glutamate pyramidal cels in PFC–> increase DA in mesolimibic system–> positive sx
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11
Q 
Which of the following antipsychotics is considered to be the most potent and thus have the highest risk of extrapyramidal symptoms? 
A.  Thioridazine
B.  Chlorpromazine 
C.  Haloperidol 
D.  Clozapine 
E.  Olanzapine
A

C.  Haloperidol

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12
Q

What is the most potent antipsychotic?

What is the least potent antipsychotic?

A

Haloperidol

Chlorpromiazine

But!
Clozapin, Olanzapine, Quetiapine, and Ziprasidone have the least EPS.

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13
Q 
Which of the following antipsychotics has been shown to be a partial agonist at the dopamine D2 receptor? 
A.  Thioridazine 
B.  Risperidone 
C.  Haloperidol
D.  Aripiprazole 
E.  Quetiapine
A

D.  Aripiprazole

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14
Q

Consistent with the dopamine theory of schizophrenia, ____ explains the most significant pharmacologic effects of antipsychotic agents.
BUT efficacy has been found in antipsychotic agents that ___ (thus reduced extrapyramidal side effects).

A

blockade of dopamine D2 receptors

block 5HT2 receptors without possessing potent blockade of D2 receptors

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15
Q

Describe Typical antipsychotics

A
  1. HIGH 2/5HT2A ratio–> good D2 block and good efficacy agains + sx
  2. High D2 block= high EP toxicity
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16
Q

Describe how high vs low CLINLCAL potencies of TYPICAL antipsychotics affect EPSE and other ADRs

A
  1. High potency: high D2 SE (EPSE) but less ADRs via M-H2-alpha1 block (ex. Haloperidol)
  2. Low potency: low EPSE but high ADRs from M-H1-alpha1 block (ex. Chlorpromazine)

**M (dry mouth, sedation), H1 (sedation), Alpha1 (hypotension)

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17
Q

Which of the following statements regarding typical antipsychotic agents is correct?
A.  Clinical potency correlates with binding to dopamine D2 receptors
B. Long-term treatment increases the firing rate of dopamine neurons
C.  Long-term treatment results in the supersensitivity of dopamine neurons
D.  The drugs differ in efficacy and potency

A

A.  Clinical potency correlates with binding to dopamine D2 receptors***

C.  Long-term treatment results in the supersensitivity of dopamine neurons

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18
Q

Describe Atypical antipsychotic agents

A
  1. LOW D2/5HT2A ratio–> reduced incidence of EPSE
  2. poor D2 block–> good efficacy in schizo
  3. Good 5HT2A block–> good efficacy against neg. sx
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19
Q

Which of the following actions distinguishes newer (atypical) antipsychotics from typical antipsychotics?
A.  Low incidence of extrapyramidal effects
B.  Selective effect on mesolimbic vs nigrostriatal dopamine neurons
C.  Little hyperprolactinemia
D.  Lower incidence of sedation
E.  Less expensive

A

A.  Low incidence of extrapyramidal effects
B.  Selective effect on mesolimbic vs nigrostriatal dopamine neurons
C.  Little hyperprolactinemia

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20
Q 
An adolescent male is newly diagnosed with schizophrenia. Which of the following antipsychotic agents may have the best chance to improve his apathy and blunted affect? 
A.  Chlorpromazine 
B.  Fluphenazine 
C.  Haloperidol 
D.  Olanzapine 
E.  Thioridazine 
F.   Clozapine
A

D.  Olanzapine
F.   Clozapine

*Atypicals are good at neg. sx

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21
Q

What are the ADRs of muscarinic block?

A

(increased w/ typical-low potency– ie. Chlorpromazine)
*No see, no pee, no spit, no shit (fast and tired)

  1. Blurred vision
  2. Urination difficulty
  3. Dry mouth
  4. Constipation
  5. Tachycardia
  6. Sedation
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22
Q

What are the ADRs of alpha1 block

A

(increased w/ typical-low potency– ie. Chlorpromazine)

1. orthostatic hypotension

23
Q

What are the ADRs of H1 histamine block

A

(increased w/ typical-low potency– ie. Chlorpromazine)

  1. Sedation
  2. Weight gain–> risk of DM2
24
Q

Which of the following therapeutic actions or side effects of antipsychotic agents does NOT result from blockade of dopamine receptors?
A.  Anti-emetic action
B.  Xerostomia
C.  Hyperprolactinemia
D.  Parkinson-like rigidity
E.  Alleviation of hallucinations and delusions
F.   Poikilothermia (interference with hypothalamic temperature regulation)
G.  Orthostatic hypotension

A

G.  Orthostatic hypotension

*caused by A1 block

25
Q

Low potency typical antipsychotic agents like chlorpromazine can have significant alpha-adrenergic receptor blocking activity. Therefore, if a patient taking chlorpromazine for schizophrenia is given epinephrine to increase blood pressure following anaphylactic shock in the clinic, one is likely to observe:
A.  Seizures
B.  Additive CNS depression
C.  A paradoxical decrease in BP due to EPI reversal
D.  Severe Parkinsonian side effects such as muscle rigidity
E.  An exaggerated, life-threatening hypertensive response

A

C.  A paradoxical decrease in BP due to EPI reversal

26
Q

What med causes increase QT interval/arrhythmias

least common w/?

A

Ziprasidone

*least w/ aripiprazole

27
Q

EPSE are highest w/ what meds

A

typical-high potency/ high D2 block (ie. Haloperidol)

28
Q

Extrapyramidal SE

A
  1. Acute dystonia (onset: 1-5 days)– totricollis, trismus, opisthmotonos
  2. Akathisia (onset 6-60days)– restless
  3. Pseduoparkinsonism (onset 5-90 days)– tremor, bradykinesia, rigidity, shuffling gait
  4. Tardive dyskinesia (onset 3-6 months)– involuntary repetitive movement of lips, tongue, arms, legs (choreathetoid movements)
  5. Piokilothermia
  6. Hyperprolactinemia
29
Q

Tx of acute dystonia seen w/ EPSE

A
  1. Anticholinergic agents (diphenhydramine-benztropine)
30
Q

Tx of akathisia seen w/ EPSE

A
  1. reduce dose
  2. change drug
  3. try anticholinergic, BB, or benozo
31
Q 
A 35-year-old male patient who is treated with haloperidol for his diagnosis of schizophrenia is considered to be well-managed symptomatically for his psychotic symptoms. However, he is reporting restlessness, the inability to sit still at the dinner table, and his family notices that he is pacing up and down the hallway frequently. Of the following, which is the best medication to treat his antipsychotic-induced akathisia? 
A.  Benztropine 
B.  Levodopa 
C.  Diphenhydramine 
D.  Dantrolene 
E.  Propranolol
A

E.  Propranolol

*tx akathisia w/ Anticholinergic, BB or benzo (or try reducing or changing)

32
Q

Tx of pseudoparkinsonism seen w/ EPSE

A
  1. anticholinergic agents
33
Q

Tx of Tardive dyskinesia seen w/ EPSE

A

rarely effective, prevention best strategy

34
Q

Tardive dyskinesia is thought to result from which of the following?
A.  Depolarization blockade of dopamine receptors
B.  Blockade of 5HT2 serotonin receptors
C.  Anticholinergic properties of the drugs
D.  Dopamine receptor supersensitivity

A

D.  Dopamine receptor supersensitivity

35
Q 
Antipsychotic agents exert both therapeutic actions and side effects as a result of dopaminergic receptor blocking activities in various brain regions.  Appetite increase, weight gain and diabetes are common side effects of antipsychotic use that result from block of dopamine receptors at which site? 
A.  Mesolimbic system 
B.  Nigrostriatal pathway 
C.  Mesocortical system 
D.  Hypothalamus 
E.  Locus ceruleus 
F.   Pituitary
A

D.  Hypothalamus

  • block of hypothalamic DA receptors
  • *Especially w/ atypical agents
36
Q

ADRs or Clozapine

A
  1. Agranulocytosis *
  2. Lower seizure threshold

*dose-related (restricted use - CBC required prior to dispensing)

37
Q

Weight gain and DM2 SE is most common w/ what drugs

A
  • especially w/ atypical agents

* monitor weight, Blood glucose and lipids

38
Q

Other ADRs from antipsychotics

A
  1. photosensitivity
  2. lowered seizure threshold
  3. Retinopathy- w/ .thioridazine
  4. Neuroleptic malignant syndrome
39
Q

How do you tx neuroleptic malignant syndrome

A
  1. dantrolene sodium

* medical emergency!

40
Q 
Which of the following side effects of antipsychotic drugs is a medical emergency and should be treated immediately? 
A.  Mild slowing of gait 
B.  Production of breast milk 
C.  Neuroleptic malignant syndrome 
D.  Constipation 
E.  Acute dystonia
A

C.  Neuroleptic malignant syndrome

41
Q 
Which antipsychotic has the most sedative potential and is sometimes used questionably as a hypnotic agent in certain clinical settins? 
A.  Haloperidol 
B.  Chlorpromazine 
C.  Quetiapine 
D.  Aripiprazole 
E.  Risperidone
A

C.  Quetiapine

42
Q

Describe the absorption and distribution of antipsychotics

A
  1. most are incompletely absorbed and undergo significant 1st pass effect
  2. extensively protein bound, can cross the placenta to exert effects in the fetus
43
Q

___ agents preferred if negative symptoms and cognition deficits plus decreased risk for EPSE

A

Atypical agents

44
Q

Use __ if refractory to other drugs

A

Clozapine

45
Q

Most patients experience equal control of positive symptoms with ___

A

either typical or atypical agents

46
Q

Weight gain and metabolic SE are highest with:

are minimal with:

A

Highest: Olanzapine, clozapine, quetiapine

Minimal: aripiprazole, lurasidone

47
Q

EPS are highest w/ __ and lower with ____

A

Highest: risperidone

Lower w/ quetiapine, iloperidone

48
Q

Sedation is minimal w/

A

aripiprazole- risperidone

*Quetiapine or olanzapine if insomina or agitation

49
Q 
Agranulocytosis (low white blood cell count) can predispose  patients to infections.  Which of the following agents used in the pharmacotherapy of mental illnesses is associated with the highest incidence of agranulocytosis as a side effect?
A.  Amitriptyline (Elavil ®) 
B.  Chlorpromazine (Thorazine®) 
C.  Clozapine (Clozaril®) 
D.  Fluoxetine (Prozac®) 
E.  Haloperidol (Haldol®)
A

C.  Clozapine (Clozaril®)

50
Q

Which statement concerning the adverse effects of antipsychotic agents is accurate?
A.  Acute dystonic reactions occur commonly with olanzapine
B.  Akathisias due to antipsychotic drugs are managed by increasing the drug dose
C.  Blurring of vision and urinary retention are common adverse effects of haloperidol
D.  The late-occurring choreoathetoid movements caused by typical antipsychotic drugs are alleviated by atropine
E.  Acute dystonic reactions occur commonly with haloperidol

A

E.  Acute dystonic reactions occur commonly with haloperidol

51
Q 
Haloperidol is NOT an appropriate drug for management of: 
A.  Acute mania 
B.  Amenorrhea-galactorrhea syndrome 
C.  Phencyclidine intoxication 
D.  Schizoaffective disorders 
E.  Tourette’s syndrome
A

B.  Amenorrhea-galactorrhea syndrome

52
Q

What are psychiatric uses of anti-psychotics

A
  1. Schizo
  2. Schizoaffective disorders
  3. Manic episode in bipolar affective disorder
  4. Tourette syndrome
  5. Tx resistant depression
53
Q

What are non-psychiatric uses of anti-psychotics

A
  1. Antiemetic (block DA receptors in CTZ)– Compazine
  2. relief of pruritis (H1 blocking)– promethazine/Phenergan
  3. preoperative sedative (H1 blocking)– promethazine/Phenergan
  4. Intractable hiccoughs (Chlorpromazine)

Pharmacology (31 decks)

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