Antipyschotics

Question 1

What are positive symptoms, give 5 examples?

Answer 1

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

Question 2

What are negative symptoms, give 4 examples?

Answer 2

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

Question 3

What are cognitive symptoms?

Answer 3

• Cognitive symptoms: Deficits in memory

and cognitive control of behaviour.

Question 4

Biological basis for symptoms in schizophrenia?

Answer 4

• 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.

Question 5

• There are 4 well-defined dopamine

pathways in the brain: what are they?

Answer 5

1. MESOLIMBIC PATHWAY
2. NIGROSTRIATAL PATHWAY
3. MESOCORTICAL PATHWAY
4. TUBEROINFUNDIBULAR PATHWAY

Question 6

MESOLIMBIC PATHWAY projects from, role, and symptoms involvement?

Answer 6

• 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.

Question 7

MESOCORTICAL PATHWAY projects from and symptoms involvement?

Answer 7

• 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.

Question 8

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

Answer 8

• 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).

Question 9

TUBEROINFUNDIBULAR PATHWAY projection and role?

Answer 9

• 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.

Question 10

List 4 CLASSICAL antipsychotics drugs?

Answer 10

• Chlorpromazine
• Fluphenazine
• Haloperidol
• Thioridazine

Question 11

List 5 atypical antipsychotic drugs?

Answer 11

• Clozapine
• Risperidone
• Olanzapine
• Quetiapine
• Aripiprazole

Question 12

Classical antipsychotics are subclassified

according to their potency:

Answer 12

• 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.

Question 13

MOA of CLASSICAL ANTIPSYCHOTIC DRUGS?

Answer 13

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

Question 14

MECHANISM OF ACTION OF

ANTIPSYCHOTICS atypical

Answer 14

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.

Question 15

COMMON PROPERTIES OF ATYPICAL ANTIPSYCHOTICS

Answer 15

• 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.

Question 16

PROPERTIES OF SOME ATYPICAL ANTIPSYCHOTIC AGENTS?

Answer 16

• 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.

Question 17

ACTIONS OF ANTIPSYCHOTIC DRUGS

Answer 17

• ANTIPSYCHOTIC

* ANTIEMETIC

Question 18

ANTIPSYCHOTIC ACTIONS of antipsychotic drugs?

Answer 18

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

Question 19

ANTIEMETIC EFFECTS of antipsychotic drugs?

Answer 19

• 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.

Question 20

METABOLISM of antipsychotic drugs?

Answer 20

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

Question 21

EXTRAPYRAMIDAL REACTIONS with antipsychotics?

Answer 21

• 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.

Question 22

EPRs include:

Answer 22

• Parkinsonism
• Dystonia
• Akathisia
• Tardive Diskynesia

Question 23

NEUROLOGIC EFFECTS

PARKINSONISM:?

Answer 23

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

Question 24

Dystonia and akathisia with antipsychotic use?

Answer 24

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.

Question 25

Tardive dyskinese with antipsychotic use?

Answer 25

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

Question 26

Tardive dyskinese management with antipsychotic use?

Answer 26

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.

Question 27

Describe neuroleptic malignant syndrome

Answer 27

``` 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. ```

Question 28

Sedation with antipsychotic use?

Answer 28

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

Question 29

Describe blockade actions of antipsychtoics in regards to AE?

Answer 29

• 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.

Question 30

TOXIC OR ALLERGIC REACTIONS with antipyschotics?

Answer 30

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

Question 31

ENDOCRINE & METABOLIC EFFECTS with antipsychotics?

Answer 31

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.

Question 32

CARDIAC TOXICITY with antipsychotics?

Answer 32

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

Question 33

OCULAR COMPLICATIONS with antipsychotics?

Answer 33

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

Question 34

ANTIPSYCHOTICS: USES?

Answer 34

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.

Question 35

NON-PSYCHIATRIC INDICATIONS of antipsychotics?

Answer 35

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

Question 36

ANTIPSYCHOTICS IN PREGNANCY

Answer 36

• 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.

Question 37

DRUG CHOICE with antipsychotics drugs?

Answer 37

• 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.