Antipsychotics

Question 1

There are 4 key pathways affected by dopamine int he brain;

1. Mesocortical
2. Mesolimbic
3. Nigrostriatal
4. Tuberoinfundibular

Expand on mesocortical

Answer 1

• projects from the ventral tegmentum (brain stem) to the cerebral cortex.
• This pathway is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise.
• Problem here for a psychotic patient, is too little dopamine

Question 2

There are 4 key pathways affected by dopamine int he brain;

1. Mesocortical
2. Mesolimbic
3. Nigrostriatal
4. Tuberoinfundibular

Expand on mesolimbic

Answer 2

• projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system.
• This pathway is where the positive symptoms come from (hallucinations, delusions, and thought disorders).
• Problem here in a psychotic patient is there is too much dopamine

Question 3

There are 4 key pathways affected by dopamine int he brain;

1. Mesocortical
2. Mesolimbic
3. Nigrostriatal
4. Tuberoinfundibular

Expand on nigrostriatal

Answer 3

• Projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia
• This pathway is involved in movement regulation.
• Remember that dopamine suppresses acetylcholine activity.
• Dopamine hypoactivity can cause Parkinsonian movements i.e. rigidity, bradykinesia, tremors), akathisia and dystonia.

Question 4

There are 4 key pathways affected by dopamine int he brain;

1. Mesocortical
2. Mesolimbic
3. Nigrostriatal
4. Tuberoinfundibular

Expand on tuberoinfundibular

Answer 4

• projects from the hypothalamus to the anterior pituitary.
• Remember that dopamine release inhibits/regulates prolactin release.
• Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia

Question 5

Antipsychotics are used to treat bipolar, cyclothymia and schizoaffective disorders.

The following classes of drugs are used;

• Lithium
• anticonvulsants
• antipsychotics

How do antipsychotics work? Give some examples

Answer 5

• Are D2 dopamine receptor antagonists
• High potency typical antipsychotics bind to the D2 receptor with high affinity. As a result they have higher risk of extrapyramidal side effects. Examples include
  
  • Fluphenazine
  • Haloperidol
  • Pimozide\
• Low potency typical antipsychotics have less affinity for the D2 receptors but tend to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects including sedation, hypotension.
• Examples include
  
  • chlorpromazine
  • Thioridazine.

Question 6

What are atypical anti-psychotics?

Answer 6

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Examples

• Clozapine
• asenapine
• olanzapine
• quetiapine
• paliperidone
• risperidone
• sertindole
• ziprasidone
• zotepine
• aripiprazole

Question 7

What are atypical anti-psychotics?

Answer 7

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Examples

• Clozapine
• asenapine
• olanzapine
• quetiapine
• paliperidone
• risperidone
• sertindole
• ziprasidone
• zotepine
• aripiprazole

Question 8

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

In what forms can you get resperidone?

Answer 8

• Available in regular tabs
• IM depot forms
• rapidly dissolving tablet

Question 9

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

In what forms can you get resperidone?

Answer 9

• Available in regular tabs
• IM depot forms
• rapidly dissolving tablet

Question 10

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

At what levels does risperidone function more like a typical antipsychotic?

Answer 10

doses greater than 6mg

Question 11

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Risperidone has which side effects?

Answer 11

• Increased extrapyramidal side effects (dose dependent)
• Most likely atypical to induce hyperprolactinemia
• Weight gain and sedation (dosage dependent)

Question 12

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Olanzapine is an atypical antipsychotic.

In what forms is it available?

Answer 12

Available in regular tabs, immediate release IM, rapidly dissolving tab, depo form

Question 13

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Olanzapine is an atypical antipsychotic.

What are the side-effects?

Answer 13

• Weight gain (can be as much as 30-50lbs with even short term use)
• May cause hypertriglyceridemia
• hypercholesterolemia
• hyperglycemia (even without weight gain)
• May cause hyperprolactinemia (< risperidone)
• May cause abnormal LFT’s (2% of all patients)

Question 14

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Quetiapine is an atypical antipsychotic.

In what forms is it available?

Answer 14

Only tablet form

Question 15

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Quetiapine is an atypical antipsychotic.

What are the side-effects?

Answer 15

• May cause abnormal LFT’s (6% of all patients)
• May be associated with weight gain, though less than seen with olanzapine
• May cause hypertriglyceridemia
• hypercholesterolemia
• hyperglycemia (even without weight gain), however less than olanzapine
• Most likely to cause orthostatic hypotension

Question 16

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Aripiprazole is an atypical antipsychotic.

In what forms is it available?

Answer 16

Available in regular tabs, immediate release IM formulation and depo form

Question 17

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Aripiprazole is an atypical antipsychotic.

What is special about its mechanism of action?

Answer 17

Unique mechanism of action as a D2 partial agonist

Question 18

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Aripiprazole is an atypical antipsychotic.

Unique mechanism of action as a D2 partial agonist

What are the side-effects?

Answer 18

• Low EPS, no QT prolongation, low sedation
• CYP2D6 (fluoxetine and paroxetine), 3A4 (carbamazepine and ketoconazole) interactions that the manufacturer recommends adjusted dosing.
• Could cause potential intolerability due to akathisia/activation.
• Not associated with weight gain

Question 19

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Clozapine is an atypical antipsychotic.

In what forms is it available?

Answer 19

Available in 1 form- a regular tablet

Question 20

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Clozapine is an atypical antipsychotic.

In which patients is this medication reserved for?

Answer 20

Is reserved for treatment resistant patients because of side effect profile but this stuff works!

Question 21

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Clozapine is an atypical antipsychotic.

Is reserved for treatment resistant patients because of side effect profile but this stuff works!

What are the side-effects?

Answer 21

• Associated with agranulocytosis (0.5-2%) and therefore requires weekly blood draws x 6 months, then Q- 2weeks x 6 months)
• Increased risk of seizures (especially if lithium is also on board)
• Associated with the most sedation, weight gain and abnormal LFT’s
• Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain

Question 22

Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole

Are all atypical antipsychotics.

• atypical agents are serotonin-dopamine 2 antagonists (SDAs)
• They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

What is the prophylactic treatment with antipsychotics?

Answer 22

• Commonest psychotic symptom is lack of insight
• People with psychotic illnesses relapse most commonly due to non compliance
• Only 30% of patients take medication as prescribed\
• After third episode of schizophrenia clear link to reduced functioning, lower IQ and negative symptoms.
• Consider Long Acting Intramuscular!!

Question 23

There are 3 broad categories of antipsychotic adverse effects;

• Tardive dyskinesia
• Neuroleptic malignant syndrome
• Extrapyramidal side effects

Expand on tardive dyskinesia

Answer 23

involuntary muscle movements that may not resolve with drug discontinuation- risk approx. 5% per year

Question 24

There are 3 broad categories of antipsychotic adverse effects;

• Tardive dyskinesia
• Neuroleptic malignant syndrome
• Extrapyramidal side effects

Expand on neuroleptic malignant syndrome

Answer 24

Characterized by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and lfts. Potentially fatal.

Question 25

There are 3 broad categories of antipsychotic adverse effects; * Tardive dyskinesia * Neuroleptic malignant syndrome * Extrapyramidal side effects Expand on extrapyramidal side effects

Answer 25

Acute dystonia, Parkinson syndrome, Akathisia

Question 26

There are 3 broad categories of antipsychotic adverse effects; * Tardive dyskinesia * Neuroleptic malignant syndrome * Extrapyramidal side effects Extrapyramidal side effects include; Acute dystonia, Parkinson syndrome, Akathisia What can you use to treat this?

Answer 26

* Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine * Dopamine facilitators such as Amantadine * Beta-blockers such as propranolol * Need to watch for anticholinergic SE particularly if taken with other meds with anticholinergic activity ie TCAs

Question 27

**Case 1** 21 yo AA male with symptoms consistent with schizophrenia is admitted because of profound psychotic sx. He is treatment naïve. You plan to start an antipsychotic- what baseline blood work would you obtain?

Answer 27

* Many atypical antipsychotics can cause dyslipidemia, abnormal LFT’s and elevated blood sugars and there is a class risk of diabetes unrelated to weight gain so you need the following: * Fasting lipid profile * Fasting blood sugar * Lfts * CBC

Question 28

**Case 1** 21 yo AA male with symptoms consistent with schizophrenia is admitted because of profound psychotic sx. He is treatment naïve. You plan to start an antipsychotic- * Many atypical antipsychotics can cause dyslipidemia, abnormal LFT’s and elevated blood sugars and there is a class risk of diabetes unrelated to weight gain so you need the following: * Fasting lipid profile * Fasting blood sugar * Lfts * CBC * His labs come back as follows: * Total Cholesterol:215 HDL:30 LDL:145 * Glucose 88 * Lfts, CBC Normal What agent would you like to start?

Answer 28

Pt has mildly elevated total cholesterol and a low HDL for his age. Would not choose Olanzapine or Quetiapine given risk of dyslipidemia. Risperidone, Ziprasidone or Aripiprazole are good choices. You start **Risperidone** and titrate to 3mg BID (high average dose).

Question 29

**Case 1** 21 yo AA male with symptoms consistent with schizophrenia is admitted because of profound psychotic sx. He is treatment naïve. You plan to start an antipsychotic- * Many atypical antipsychotics can cause dyslipidemia, abnormal LFT’s and elevated blood sugars and there is a class risk of diabetes unrelated to weight gain so you need the following: * Fasting lipid profile * Fasting blood sugar * Lfts * CBC * His labs come back as follows: * Total Cholesterol:215 HDL:30 LDL:145 * Glucose 88 * Lfts, CBC Normal You start **Risperidone** and titrate to 3mg BID (high average dose). He starts to complain that he “feels uncomfortable in my skin like I can’t sit still”. What is likely going on and what are you going to do about it?

Answer 29

* He is likely experiencing akathisia. * This is not uncommon with Risperidone. Given he was very ill reducing the dose may not be the best choice so likely treat with an **anticholinergic** agent or propranolol. * You need to treat akathisia because it is associated with an increase risk for suicide!