Anti-Psychotics (Atypical)

Question 1

What are 6 drugs that fall under the class of atypical antipsychotics?

Answer 1

Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone and Ziprasidone.

Question 2

How are the AAP’s metabolized?

Answer 2

Extensive CYP first pass metabolism followed by 2nd pass conjugation (exceptions: Asenapine, paliperidone and ziprasidone).

Question 3

Why is this class called the “atypical antipsychotics?”

Answer 3

Unlike the typical variant, this class doesn’t have as high an affinity for the D2R, but instead have a higher affinity for the 5-HT2’s.

Question 4

Why is dosage important in terms of AAS usage?

Answer 4

At low enough dose where less than 60% of D2R’s are blocked, there is good antipsychotic effect. However at greater than 80% D2R affinity we also get the associated EPS.

Question 5

Whats important about the dosage of the drug “Risparidone?”

Answer 5

It induces 80% of D2R’s at its tx range, so it has an increased propensity of causing EPS.

Question 6

How do the 5-HT2 receptors get blocked by the AAP’s?

Answer 6

Technically atypical antipsychotics do not block these receptors, they use the “Inverse agonism” concept, meaning they hold these receptors in their “off” position so they might as well be blocked.

Question 7

What is the highest receptor affinity for Chlorpromazine

Answer 7

Alpha 1 and 5 HT2 receptors followed by the D2 and D1 receptors.

Question 8

What is the receptor affinity for Haloperidol?

Answer 8

High D2R affinity, followed by alpha 1 and then everything else.

Question 9

What is the receptor affinity for clozapine?

Answer 9

D4 and alpha 1 receptors, the rest are less so (D2 and D1 are the least).

Question 10

What is the receptor affinities for Olanzapine, Aripiprazole and Quetiapin?

Answer 10

Olanzapine prefers 5-HT2, Aripiprazole likes both D2 and 5HT2 equally, and quetiapine prefers H1 receptors.

Question 11

What are AAS notorious for (even though they are not causing EPS) and which two drugs in particular?

Answer 11

This class causes weight gain. Clozapine and Olanzapine are both notorious for causing weight gain with increased blood glucose and lipids (as a consequence of weight gain).

Question 12

What is the Tx and MOA of Clozapine?

Answer 12

MOA is blockade of D4 and 5HT2 receptors resulting in tx of positive and neg symptoms with decreased propensity to cause EPS. However, CLOZAPINE’S ONLY TX USE IS FOR TX RESISTANT SCHIZOS, because it has a lot of AE’s

Question 13

How is Clozapine metabolized?

Answer 13

1A2, plus others.

Question 14

Whats special about CYP 1A2? Esp with relation to clozapine? Which drugs inhibit 1A2?

Answer 14

It is induced by cig smoking, so smokers will have high metabolism of clozapine, and patients with mania tend to smoke. Cypro, Theophylline and Fluvoxamine inhibit 1A2.

Question 15

What are the AE’s of clozapine?

Answer 15

Significant weight gain, sedation, anticholinergic effects, seizures, myocarditis, agranulocytosis, and atropine like poisoning at high doses.

Question 16

What is the MOA of Respiradone?

Answer 16

HT2 and D2R antagonism as well as alpha 1 and H1 receptor antagonism.

Question 17

When would we use Respiradone?

Answer 17

Schizo, acute mania, and maintenance of bipolar disorder. Also irritability and aggression associated with autism.

Question 18

What are the AE’s of Respiradone?

Answer 18

Akanthasia (restlessness), EPS at higher doses, prolactin elevating effects, orthostatic hypotension.

Question 19

What is “Palperidone”?

Answer 19

Active metabolite of respiradone and has similar properties as respiradone.

Question 20

What is “Olanzapine?”

Answer 20

Analog of clozapine but fewer autonomic AEs and no reports of agranulocytosis (which is a big problem with clozapine).

Question 21

MOA of Olanzapine?

Answer 21

x2 affinity for HT2 as opposed to D2, but also hits H1 M and alpha 1 Receptors (to a lesser degree than clozapine).

Question 22

Uses of Olanzapine?

Answer 22

Schizos, acute agitation and bipolar disorder.

Question 23

What are the AE’s of Olanzapine?

Answer 23

Significant weight gain, sedation, decreased seizure threshold, orthostatic hypotension increased QT intervals (possible arrythmias), and EPS at higher doses.

Question 24

What is “Quetiapine?”

Answer 24

Another analog of Clozapine, however it causes less weight gain than clozapine and olanzapine. BASICALLY, USE QUETIAPINE FOR BIPOLAR DISORDERS but can also use for schizos.

Question 25

Tx uses of Quetiapine?

Answer 25

Schizo, depression induced by bipolar disorder, acute manic episodes associated with bipolar disorder I, and maintenance tx of bipolar disorder I (adjunct).

Question 26

What are the AE’s of Quetiapine?

Answer 26

Weight gain (milder than clozapine and olanzapine), sedation, increased plasma cholesterol and TG’s, QT prolongation.

Question 27

What’s special to note about Ziprasidone?

Answer 27

Not only does it block D2/HT2, it also blocks HT2A, 2C, 1D receptors and is a HT1 AGONIST (which is inhibitory). Furthermore it is a 5-HT and NE reuptake inhibitor so it has some antidepressant and anxiolytic effects as well in pt’s with psychotic disorders.

Question 28

Uses of Ziprasidone?

Answer 28

Schizo, acute agitation in schizo patients, acute mania of bipolar, and adjunct to maintenance of bipolar.

Question 29

What is a big AE of ziprasidone?

Answer 29

QT elongation that is related to malignant ventricular arrythmias and death.

Question 30

What is Ziprasidone CI-ed for?

Answer 30

Other drugs that cause QT prolongation, such as Thioridazine, Pimozide, anti arrythmics (quinidine, amiodorone), and a few antimalarials (quinine, artemether, lumefantrine).

Question 31

What is interesting about the MOA of Aripiprazole? How does this relate to EPS?

Answer 31

It is a PARTIAL AGONIST of D2 receptors, and a PARTIAL AGONIST of 5 HT1A receptors (which, recall, is inhibitory). It is an antagonist of HT2. It hits D2 equally with 5 HT2. The partial agonist effect means it will induce a less than maximal effect of the activation of D2 receptors, thus less propensity of EPS.

Question 32

When would we use Aripiprazole?

Answer 32

Schizo, acute agitation, bipolar disorder I, MDD (adjunct), irritability associated with autistic disorders.

Question 33

What are the AE’s of Aripiprazole?

Answer 33

Headache, insomnia, agitation, dose related akanthesia and sedation.