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Pharmacology > Antipyschotics > Flashcards

Antipyschotics Flashcards

1
Q

What are positive symptoms, give 5 examples?

A 
• Positive symptoms: reflect an excess of
normal functions.
• Hallucinations and delusions
• Thought disorder
• Perceptual disturbances
• Incongruous mood
• Increased motor function
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2
Q

What are negative symptoms, give 4 examples?

A 
• Negative symptoms: reflect diminution or
loss of normal functions.
• Blunted affect
• Poverty of speech
• Diminished motivation
• Social withdrawal
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3
Q

What are cognitive symptoms?

A

• Cognitive symptoms: Deficits in memory

and cognitive control of behaviour.

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4
Q

Biological basis for symptoms in schizophrenia?

A

• Positive symptoms are believed to be linked to
overactivity of the mesolimbic pathway.
• Negative and cognitive symptoms may be due to
hypoactivity of the mesocortical pathway.

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5
Q

• There are 4 well-defined dopamine

pathways in the brain: what are they?

A
  1. MESOLIMBIC PATHWAY
  2. NIGROSTRIATAL PATHWAY
  3. MESOCORTICAL PATHWAY
  4. TUBEROINFUNDIBULAR PATHWAY
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6
Q

MESOLIMBIC PATHWAY projects from, role, and symptoms involvement?

A

• Projects from midbrain to limbic system.
• Important role in emotional behaviours.
• Hyperactivity of this pathway is thought to cause
positive psychotic symptoms.
• Blockade of D2 receptors in this pathway
decreases positive symptoms.

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7
Q

MESOCORTICAL PATHWAY projects from and symptoms involvement?

A

• Projects from midbrain to prefrontal cortex.
• Negative and cognitive symptoms may be due to
reduced activity of this pathway.
• Blockade of D2 receptors in this pathway
may cause or worsen negative and cognitive
symptoms.

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8
Q

NIGROSTRIATAL PATHWAY projects to, role, receptors and ae related to this pathway?

A

• Projects from substantia nigra to basal ganglia.
• It controls motor movements.
• Blockade of D2 receptors in this system may
lead to disorders of movement.
• This pathway is part of the extrapyramidal
nervous system.
• Motor adverse effects associated with blockade
of dopamine receptors in this system are called
extrapyramidal reactions (EPR).

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9
Q

TUBEROINFUNDIBULAR PATHWAY projection and role?

A

• Projects from hypothalamus to anterior pituitary.
• Dopamine released from these neurons inhibits
prolactin secretion.
• Blockade of dopamine receptors in this
system will increase prolactin levels.
• This may cause galactorrhea.

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10
Q

List 4 CLASSICAL antipsychotics drugs?

A
  • Chlorpromazine
  • Fluphenazine
  • Haloperidol
  • Thioridazine
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11
Q

List 5 atypical antipsychotic drugs?

A
  • Clozapine
  • Risperidone
  • Olanzapine
  • Quetiapine
  • Aripiprazole
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12
Q

Classical antipsychotics are subclassified

according to their potency:

A

• High-potency drugs: Fluphenazine and
haloperidol. More likely to produce EPRs.
• Low-potency drugs: Chlorpromazine and
thioridazine. Less likely to produce EPRs and
more likely to produce sedation and postural
hypotension.

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13
Q

MOA of CLASSICAL ANTIPSYCHOTIC DRUGS?

A

CLASSICAL ANTIPSYCHOTIC DRUGS
• The efficacy of the traditional neuroleptic drugs
correlates closely with their ability to block D2
receptors in the mesolimbic pathway.

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14
Q

MECHANISM OF ACTION OF

ANTIPSYCHOTICS atypical

A

ATYPICAL ANTIPSYCHOTIC DRUGS
• Atypical antipsychotic drugs have higher
affinities for other receptors than for the D2
receptor. For example:
• Clozapine has high affinity for D1, D4, 5HT2,
muscarinic and alpha-adrenergic receptor, but it is
also a D2 blocker.
• Risperidone blocks 5HT2 to a greater extent
than it does D2.

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15
Q

COMMON PROPERTIES OF ATYPICAL ANTIPSYCHOTICS

A

• Dual antagonism at 5-HT2A and D2 receptors.
• Part of their action is due to 5HT receptor
blockade.
• Less likely to cause EPRs than classical agents.
• Less likely to cause tardive dyskinesia
• Less likely to cause increases in prolactin
• More effective at treating negative symptoms.
• Effective in refractory populations.

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16
Q

PROPERTIES OF SOME ATYPICAL ANTIPSYCHOTIC AGENTS?

A

• Clozapine is the prototype of the atypical agents.
• Risperidone causes EPR. Rare at therapeutic doses.
• Clozapine and quetiapine are the agents least
likely to induce EPR.
• Aripiprazole is a partial agonist at D2 and 5HT1A
receptors and an antagonist at 5HT2A receptors.

17
Q

ACTIONS OF ANTIPSYCHOTIC DRUGS

A
  • ANTIPSYCHOTIC

* ANTIEMETIC

18
Q

ANTIPSYCHOTIC ACTIONS of antipsychotic drugs?

A
  • Reduce hallucinations and agitation.
  • Have a calming effect.
  • Do not depress intellectual function.
  • Motor incoordination is minimal.
  • Onset of antipsychotic action is ≤ 24 h.
19
Q

ANTIEMETIC EFFECTS of antipsychotic drugs?

A

• With the exception of aripiprazole and
thioridazine, most antipsychotics have
antiemetic effects.
• Mediated by blockade of D2 receptors of the
chemoreceptor trigger zone of the medulla.

20
Q

METABOLISM of antipsychotic drugs?

A

• Most antipsychotic drugs are almost completely
metabolized, mainly by CYP2D6, CYP1A2 and
CYP3A4.
• Antipsychotics do not interfere with the
metabolism of other drugs

21
Q

EXTRAPYRAMIDAL REACTIONS with antipsychotics?

A

• Associated with high D2 potency.
• Most likely to occur with high-potency conventional antipsychotics, such as haloperidol and fluphenazine, that have a high affinity for
D2-receptors.
• Less likely with low-potency conventional
antipsychotic drugs such as chlorpromazine or
thioridazine.
• EPRs are also less likely to occur with conventional agents with strong anticholinergic activity, such as thioridazine and
chlorpromazine.
• Atypical antipsychotic drugs have low potential
for causing EPRs.

22
Q

EPRs include:

A
  • Parkinsonism
  • Dystonia
  • Akathisia
  • Tardive Diskynesia
23
Q

NEUROLOGIC EFFECTS

PARKINSONISM:?

A

• Parkinsonism can be treated with antimuscarinic
drugs like benztropine or trihexyphenidyl, with
diphenhydramine, or with amantadine.
• Levodopa should never be used in these
patients.

24
Q

Dystonia and akathisia with antipsychotic use?

A

DYSTONIA
• Dystonia can be controlled with benztropine,
trihexyphenidyl, or diphenhydramine.

AKATHISIA
• Management requires reduction of dosage or a
change of the antipsychotic drug.
• The drugs most commonly used to manage
akathisia are clonazepam or propranolol.
25
Q

Tardive dyskinese with antipsychotic use?

A 
TARDIVE DYSKINESIA
• Late-occurring syndrome of abnormal
choreoathetoid movements.
• Most important unwanted effect of
antipsychotics.
• Potentially irreversible.
• May be due to dopamine receptor upregulation.
26
Q

Tardive dyskinese management with antipsychotic use?

A

TARDIVE DYSKINESIA: MANAGEMENT
• Discontinue antipsychotic drug or reduce dose.
• Eliminate all drugs with central anticholinergic
action.
• The VMAT inhibitors tetrabenazine or
valbenazine can be used to treat tardive
dyskinesia.
• Administration of a benzodiazepine may help.
• Clozapine is recommended for patients with
tardive dyskinesia who require antipsychotics.

27
Q

Describe neuroleptic malignant syndrome

A 
NEUROLEPTIC MALIGNANT SYNDROME
• Rare and life-threatening disorder.
• Rigidity, tremor, hyperthermia
• Altered mental status
• Autonomic instability
• Elevated WBC, elevated CK
• Myoglobinemia, with potential nephrotoxicity.
• Dantrolene or bromocriptine may be helpful.
28
Q

Sedation with antipsychotic use?

A

SEDATION
• More likely with low-potency antipsychotics and
with the atypical agents.
• Due to blockade of central H1 receptors.

29
Q

Describe blockade actions of antipsychtoics in regards to AE?

A

• Blockade of alpha1 receptors causes orthostatic
hypotension and impaired ejaculation.
• Some antipsychotics block muscarinic receptors,
producing anticholinergic effects.
• Antimuscarinic effects are beneficial in relation to EPRs.

30
Q

TOXIC OR ALLERGIC REACTIONS with antipyschotics?

A

• Clozapine causes agranulocytosis in 1-2% of
patients.
• Regular blood cell counts are mandatory.

31
Q

ENDOCRINE & METABOLIC EFFECTS with antipsychotics?

A

PROLACTIN SECRETION
• Blockade of D2 receptors in the pituitary leads to
increase in prolactin secretion.
• In women: amenorrhea-galactorrhea syndrome
and infertility.
• In men: loss of libido, infertility and impotence.
• Atypical antipsychotics are less likely to produce
prolactin elevations
WEIGHT GAIN
• Some atypical antipsychotics produce more weight gain and increases in lipids than some typical agents.
• Adverse effects of weight gain include type 2
DM, hypertension and hyperlipidemia.

32
Q

CARDIAC TOXICITY with antipsychotics?

A

• Thioridazine causes a high incidence of QTcand T-wave changes and may rarely produce ventricular arrhythmias and sudden death.

33
Q

OCULAR COMPLICATIONS with antipsychotics?

A

• Chlorpromazine causes deposits in the cornea
and lens.
• Thioridazine causes retinal deposits.

34
Q

ANTIPSYCHOTICS: USES?

A

PSYCHIATRIC INDICATIONS
• Schizophrenia.
• Bipolar disorder.
• Suppression of tics in Tourette’s disorder.
• Control of disturbed behavior in Alzheimer’s
disease.
• Adjuncts to antidepressants in treatmentresistant major depression.
• In combination with antidepressants in psychotic
depression.
• Irritability associated with autistic disorder.

35
Q

NON-PSYCHIATRIC INDICATIONS of antipsychotics?

A

• Nausea and vomiting.
• Droperidol is used in combination with fentanyl
in neurolept-anesthesia.

36
Q

ANTIPSYCHOTICS IN PREGNANCY

A

• Antipsychotic drugs are category C.
• Only clozapine is category B.
• The risk of hyperglycemia and weight gain,
which may be problematic in pregnancy, is
greater with atypical antipsychotics.

37
Q

DRUG CHOICE with antipsychotics drugs?

A

• Atypical drugs are preferred due to:
• Benefit for negative symptoms and cognition
• Diminished risk of EPRs and tardive dyskinesia
• Lesser increases in prolactin levels
• Aripiprazole is currently the most prescribed
antipsychotic in the US.
• Clozapine, because of its potential for
agranulocytosis is reserved for refractory patients.

Pharmacology (49 decks)

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