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Pharmacology 2 EXAM > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

What causes schizophrenia?

A

Dysfunction of the mesolimbic or mesocortical dopaminergic neuronal pathway.

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2
Q

List the positive symptoms of schizophrenia. Why are they called that way?

A
  1. Delusions.
  2. Hallucinations (mostly auditory).
  3. Speech and thinking disturbances.
  4. Inappropriate emotions.

Positive symptoms are abnormal experiences or behaviors added to normal functioning.

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3
Q

List the negative symptoms of schizophrenia. Why are they called that way?

A
  1. Blunted emotions.
  2. Anhedonia.
  3. Lack of feeling.

Negative symptoms are the loss or reduction of normal functions.

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4
Q

Which type of hallucinations is most common in schizophrenia?

A

Auditory hallucinations.

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5
Q

What are the consequences of negative symptoms in schizophrenia?

A
  1. Loss of motivation.
  2. Social withdrawal.
  3. Suicidal ideation.
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6
Q

Does a schizophrenic person have insight into their disorder?

A

No, they do not believe they are schizophrenic.

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7
Q

Name two cognitive consequences of schizophrenia.

A

Impaired processing of new learning and memory issues.

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8
Q

What percentage of the general population has schizophrenia?

A

1%.

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9
Q

When does schizophrenia typically affect people?

A

During late adolesence or early adulthood.

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10
Q

Is the prevalence of schizophrenia equal in men and women?

A

Yes, it is equal.

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11
Q

What is a key characteristic of schizophrenic regarding genetics?

A

It has a strong genetic component.

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12
Q

What does the dopamine hypothesis of schizophrenia suggest?

A

Increased dopamine activity can lead to schizophrenia-like symptoms.

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13
Q

Which drugs can cause stimulant-induced psychosis?

A

Amphetamines and cocaine.

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14
Q

What effect do amphetamines have on people with schizophrenia in remission?

A

Low doses can trigger psychotic reactions.

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15
Q

How does stress relate to schizophrenia?

A

Stress can induce psychotic episodes in people who have recovered from amphetamine addiction.

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16
Q

What names do antipsychotics go by?

A
  • Neuroleptics.
  • Major tranquilizers.
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17
Q

What is the primary use of antipsychotics?

A

To treat schizophrenia.

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18
Q

Do antipsychotics cure schizophrenia?

A

No, they only decrease symptoms by reducing dopaminergic and/or serotonergic neurotransmission.

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19
Q

What do antipsychotics decrease in schizophrenia patients?

A

The intensity of hallucinations and delusions.

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20
Q

How are antipsychotics classified?

A
  • First-generation antipsychotics:
    1. Low potency.
    2. High potency.
  • Second-generation antipsychotics.
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21
Q

What does the classification of first-generation antipsychotics indicate?

A

The affinity for the dopamine D2 receptor, and the adverse effect profile, not clinical effectiveness.

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22
Q

What is the mechanism of action for first-generation antipsychotics?

A

Competitive blocking of D2 dopamine receptors.

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23
Q

Name the most common side effect associated with first-generation anti-psychotics.

A

Movement disorders (EPS).

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24
Q

What is an example of a common high potency 1st generation antipsychotic that causes EPS due to binding tightly to dopaminergic neuroreceptors?

A

Haloperidol.

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25
Q

What is an example of a common low potency 1st generation antipsychotic that binds weakly to dopaminergic neuroreceptors and is less likely to cause EPS symptoms?

A

Chlorpromazine.

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26
Q

Is any one first-generation antipsychotic more effective than another?

A

No, no one drug is clinically more effective than another.

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27
Q

What are the most common low potency first-generation antipsychotics?

A
  • Chlorpromazine.
  • Prochlorperazine.
  • Thioridazine.
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28
Q

What are the most common high potency first-generation antipsychotics?

A
  • Fluphenazine.
  • Haloperidol.
  • Pimozide.
  • Thiothixene.
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29
Q

What are the most common second-generation antipsychotics?

A
  • Aripiprazole.
  • Clozapine.
  • Olanzapine.
  • Quetiapine.
  • Risperidone.
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30
Q

What are second-generation antipsychotics also known as?

A

Atypical antipsychotics.

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31
Q

What is the side effects profile of second-generation antipsychotics?

A

Fewer EPS symptoms compared to first-generation antipsychotics. However, they are associated with a higher risk of metabolic side effects, such as:
- Diabetes.
- Hypercholesterolemia.
- Weight gain.

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32
Q

What affects the drug selection of antipsychotics?

A
  • The risk of movement disorders (1st gen > 2nd gen).
  • Individual patient response.
  • Comorbid conditions.
  • The non-interchangeable nature of second-generation antipsychotics.
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33
Q

What is the mechanism of action of second-generation antipsychotics?

A
  1. Dopamine-receptor blocking activity in the brain.
  2. Serotonin-receptor blocking activity in the brain.
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34
Q

How many types of dopamine receptors are there? And which are excitatory and which are inhibitory?

A

There are 5 types of dopamine receptors: D1, D2, D3, D4, and D5:
- D1 and D5 are excitatory.
- D2, D3, and D4 are inhibitory.

Neuroleptic drugs bind to these receptors to varying degrees.

35
Q

Which dopamine receptor subtype blocking is associated with the clinical efficacy of antipsychotics?

A

The ability to block D2 receptors in the mesolimbic system is associated with antipsychotics’ clinical efficacy.

36
Q

Compare haloperidol and chlorpromazine in their potency towards the D2 receptor.

A

Haloperidol is 100 times more potent towards D2 receptor than chlorpromazine.

37
Q

Describe the affinity of clozapine.

A

The atypical antipsychotic clozapine has a higher affinity for the D4 receptor and lower affinity to D2 receptor.

38
Q

Which drugs antagonize the actions of antipsychotic drugs? And how do they do that?

A
  • Levodopa.
  • Amphetamines.
  • Bromocriptine.
    They increase dopamine activity, counteracting the dopamine receptor blocking effect of antipsychotics.
39
Q

Which 5-HT serotonin receptor subtype is most commonly inhibited by second-generation antipsychotics?

A

5-HT2A.

40
Q

Which receptors does clozapine have a high affinity for?

A

D1, D4, 5-HT2, muscarinic, and alpha-adrenergic.
Also, a weak dopamine D2 receptor antagonist.

41
Q

What is the primary receptor blocked by risperidone?

A

5-HT2A receptors (more than D2 receptors).

42
Q

What receptors does aripiprazole partially agonize and block?

A

Partial agonist at D2 receptors and 5-HT1A receptors; but a blocker of 5-HT2A receptors.

43
Q

What receptors does quetiapine primarily block?

A

D2 receptors (more than 5-HT2A receptors).

44
Q

What are the antipsychotic actions of antipsychotics due to?

A

The blocking of dopamine and/or serotonin receptors.

45
Q

How do antipsychotics affect schizophrenia symptoms?

A

They primarily reduce the positive symptoms, such as hallucinations and delusions.

They reduce the negative symptoms associated with schizophrenia (such as anhedonia, blunted affect, etc.) to a lesser extent.

46
Q

Why do the effects of antipsychotics usually take several days to weeks to occur?

A

The therapeutic effect is related to secondary changes in the corticostriatal pathway.

47
Q

Which second-generation agents ameliorate the negative symptoms of schizophrenia to some extent?

A

Clozapine.

48
Q

All of second-generation antipsychotics have a calming effect and reduce spontaneous physical movement.

A

True.

49
Q

In what way are antipsychotics better than CNS depressants such as barbiturates?

A

They do not depress the intellectual functioning of the patient as much, and motor coordination difficulties are minimal.

50
Q

What are the extrapyramidal effects associated with antipsychotics?

A
  1. Dystonia: sustained contraction of muscles leading to twisting and distorted posture.
  2. Akathisia: motor restlessness.
  3. Tardive dyskinesia: involuntary movements of the tongue, lips, neck, trunk, and limbs.
51
Q

What causes the extrapyramidal effects associated with antipsychotics?

A

Blocking of dopamine receptors in the nigrostriatal pathway probably causes these unwanted movement symptoms.

52
Q

Which antipsychotic drugs lack antiemetic effects?

A
  • Aripiprazole (partial D2 agonist).
  • Thioridazine.
53
Q

How do antipsychotics also exert an antiemetic effect?

A

By blocking D2-dopaminergic receptors of the chemoreceptor trigger zone of the medulla.

54
Q

What are the anticholinergic effects associated with antipsychotics?

A
  • Blurred vision.
  • Dry mouth.
  • Confusion.
  • Constipation.
  • Urinary retention.
55
Q

Which antipsychotic increases salivation?

A

Clozapine.

56
Q

Which antipsychotic most commonly causes constipation and urinary retention?

A

Chlorpromazine.

57
Q

Which antipsychotics are associated with anticholinergic effects?

A

Thioridazine.
Chlorpromazine.
Clozapine.
Olanzapine.

58
Q

What side effects, aside from anti-cholinergic, do antipsychotics exhibit?

A
  1. Orthostatic hypotension and light-headedness due to the blocking of alpha-adrenergic receptors.
  2. Poikilothermia.
  3. Increased prolactin release due to D2 receptor blocking in the pituitary gland.
  4. Sedation due to histamine receptor antagonism (chlorpromazine, olanzapine, clozapine).
  5. Sexual dysfunction.
59
Q

Why do antipsychotics cause orthostatic hypotension and light-headedness?

A

Due to the blocking of alpha-adrenergic receptors.

60
Q

Why do antipsychotics release prolactin release?

A

Due to D2 receptor blocking in the pituitary gland.

61
Q

Why do antipsychotics cause sedation?

A

Due to histamine receptor antagonism (chlorpromazine, olanzapine, clozapine).

62
Q

Describe the efficacy of antipsychotics in the treatment of schizophrenia.

A

Not all patients response to the treatment in the same way; complete normalization of behavior is seldom achieved.

First-generation antipsychotics alleviate the positive symptoms of schizophrenia MORE than second-generation antipsychotics.

Second-generation antipsychotics alleviate the negative symptoms MORE than first-generation antipsychotics (but not consistent).

Patients resistant to first-generation antipsychotics are advised to switch to second-generation antipsychotics.

63
Q

Why is clozapine reserved for the treatment of schizophrenics who do not respond to other neuroleptics?

A

Because it is associated with blood dyscrasia, and other severe side effects, such as bone marrow suppression, which causes severe agranulocytosis, so white blood cell # should be monitored.

64
Q

Which antipsychotic is most commonly used for severe drug-induced nausea?

A

Prochlorperazine.

65
Q

What are we recommended to use to treat nausea and vomiting instead of antipsychotics?

A

Scopolamine.

66
Q

How can we use antipsychotics to treat chronic pain with severe anxiety?

A

By combining them with narcotic analgesics.

67
Q

Which antipsychotic is used to treat intractable hiccups?

A

Chlorpromazine.

68
Q

Which antipsychotic is used to treat pruritis?

A

Promethazine due to its antihistamine effect.

69
Q

Which antipsychotics are used to treat the motor and phonic tics of Tourette’s disorder?

A
  • Pimozide.
  • Haloperidol.
70
Q

Which antipsychotics are used to treat disruptive behavior and irritability secondary to autism?

A
  • Risperidone.
  • Aripiprazole.
71
Q

What are the pharmacokinetics of antipsychotics?

A

They have a variable absorption and readily pass into the brain. They have a large volume of distribution.

They are also available as long-acting injectables (LAIs) that have a duration of up to 2 to 4 weeks. They are often used to treat outpatients who are noncompliant with oral medications.

72
Q

How are long-acting injectable (LAIs) antipsychotics better in their side effect profile?

A

They exhibit lower extrapyramidal symptoms and little physical dependence.

73
Q

How do the extrapyramidal effects associated with antipsychotics occur on the physiological level?

A

The inhibitory effects of dopaminergic neurons is normally balanced by the excitatory actions of cholinergic neurons in the striatum.

However, when dopamine receptors are blocked by antipsychotics, a relative excess of cholinergic influence occurs; resulting in extrapyramidal motor effects.

74
Q

What affects the types and severity of extrapyramidal symptoms associated with antipsychotics?

A

Time and dose:
- Dystonia: few hours to days.
- Akathisia: days to weeks.
- Second-Parkinsonism: weeks to months.
- Tardive dyskinesia: months to years.

75
Q

How can we reduce ESP symptoms in patients who take antipsychotics?

A

By blocking cholinergic activity through the administration of anticholinergic drugs such as benztropine.

76
Q

Why are clozapine and risperidone ahead of old agents in treating schizophrenia and lower tardive dyskinesia?

A

Because of the 5-HT2A antagonizing effect.

77
Q

Which second-generation antipsychotic is used as a first line?

A

Risperidone.

78
Q

Is tardive dyskinesia reversible?

A

Sometimes, a prolonged holiday diminishes tardive dyskinesia, however, sometimes it is irreversible and may not diminish even after discontinuing the drug.

79
Q

How does the tardive dyskinesia associated with antipsychotics occur on the physiological level?

A

The tardive dyskinesia is a compensatory response to longer neuroleptic treatment as a result of increased number of dopamine receptors and neuron supersenstivity, which results overpowers cholinergic input and causes excess movement.

80
Q

What is antipsychotic malignant syndrome?

A

A potentially fatal syndrome that manifests in muscle rigidity, fever, altered mental status, stupor, unstable blood pressure, and myoglobinemia.

81
Q

How is antipsychotic malignant syndrome treated?

A
  • Drug must be discontinued.
  • Dantrolene or bromocriptine may be helpful.
82
Q

What are the side effects of antipsychotics associated with the hypothalamus?

A
  • Amenorrhea.
  • Galactorrhea.
  • Gynecomastia.
  • Infertility.
  • Impotence.
83
Q

What are the cautions and contraindications of antipsychotics?

A

Acute agitation that accompanies withdrawal from alcohol or other drugs may be aggravated by the use of antipsychotics.

All antipsychotics have the potential to lower the seizure threshold, so they should be used with caution in patients who have seizure disorders.

Additionally, the use of clozapine carries a risk of agranulocytosis.

84
Q

What is the maintenance treatment of antipsychotics like?

A
  • Two or more psychotic episodes -> maintenance therapy for at least 5 years.
  • Higher doses -> lower relapse.
  • 2nd generation -> lower relapse.

Pharmacology 2 EXAM (6 decks)

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