Antipsychotics

Question 1

Define psychosis and appreciate schizophrenia as one common form of psychosis

Answer 1

Psychosis: means delusions and/or psychotic hallucinations

Question 2

List the major positive and negative symptoms of schizophrenia

Answer 2

+auditory hallucinations
+delusions
+disorganized speech
+disorganized behavior

• flat effect
• social withdrawal
• lack of motivation
• lack of speech/thought

Question 3

Briefly describe the dopamine hypothesis of psychosis

Answer 3

All current antipsychotic drugs block DA neurotransmission

Drugs that release DA from terminals and DA agonists can cause psychotic symptoms

Question 4

Compare/contrast first and second generation antipsychotics regarding their affinity for D2 and 5-HT2A receptors

Answer 4

1st generation =
D2 antagonists

2nd generation =
D2 + 5HT2A antagonists
(Some efficacy against negative symptoms)

Question 5

Describe MOA and clinical use of:

Haloperidol

Answer 5

D2 antagonist

Indication: clearly effective for positive symptoms

Question 6

Describe MOA and clinical use of:

Trifluperazine

Answer 6

D2 antagonist

Indication: clearly effective for positive symptoms

Question 7

Describe MOA and clinical use of:

Fluphenazine

Answer 7

D2 antagonist

Indication: clearly effective for positive symptoms

Question 8

Describe MOA and clinical use of:

Chlorpromazine

Answer 8

D2 antagonist

Indication: clearly effective for positive symptoms

(Low potency 1st gen.)

Question 9

Describe MOA and clinical use of:

Thioridazine

Answer 9

D2 antagonist

Indication: clearly effective for positive symptoms

(Low potency 1st gen)

Question 10

Describe MOA and clinical use of:

Clozapine

Answer 10

D2 antagonist

5HT2A antagonist

Question 11

Describe MOA and clinical use of:

Quetiapine

Answer 11

D2 antagonist

5HT2A antagonist

Question 12

Describe MOA and clinical use of:

Olanzapine

Answer 12

D2 antagonist

5HT2A antagonist

Question 13

Describe MOA and clinical use of:

Aripriprazole

Answer 13

PARTIAL D2 agonist

5HT2A antagonist

Question 14

Describe MOA and clinical use of:

Risperidone

Answer 14

D2 antagonist

5HT2A antagonist

Question 15

Describe MOA and clinical use of:

Ziprasidone

Answer 15

D2 antagonist

5HT2A antagonist

Question 16

Describe major AEs of:

Haloperidol

Answer 16

EPS (acute and chronic)

Question 17

Describe major AEs of:

Trifluperazine

Answer 17

EPS (acute and chronic)

Question 18

Describe major AEs of:

Fluphenazine

Answer 18

EPS (acute and chronic)

Question 19

Describe major AEs of:

Chlorpromazine

Answer 19

EPS (acute and chronic)

Question 20

Describe major AEs of:

Thioridazine

Answer 20

EPS (acute and chronic)

Question 21

Describe major AEs of:

Clozapine

Answer 21

Agranulocytosis
(No neutrophils)

Seizures

Salivation

Question 22

Describe major AEs of:

Quetiapine

Answer 22

Less AE than other 2nd generation antipsychotics

Question 23

Describe major AEs of:

Olanzapine

Answer 23

Most problematic for weight gain and metabolic changes

Question 24

Describe major AEs of:

Aripiprazole

Answer 24

Less AE than other 2nd generation antipsychotics

Question 25

Describe major AEs of: Risperidone

Answer 25

WORSE than other 2nd generation antipsychotics in terms of increasing prolactin secretion and causing EPS

Question 26

Describe major AEs of: Ziprasidone

Answer 26

Causes QT prolongation

Question 27

What are the first generation (aka typical) antipsychotics?

Answer 27

Haloperidol Trifluperazine Fluphenazine Chlorpromazine Thioridazine

Question 28

What are second generation (aka atypical) antipsychotics?

Answer 28

Clozapine Quetiapine Olanzapine Aripiprazole Risperidone Ziprasidone

Question 29

Compare and contrast positive/negative symptoms regarding their responsiveness to antipsychotic drugs

Answer 29

Most treat positive Clozapine works against negative symptoms

Question 30

Define one major location of 5-HT2A R's and correlate drugs with an affinity for these receptors with the incidence of extrapyramidal side effects

Answer 30

Nigrostriatal pathway 2nd generation antipsychotics will help decrease EPS

Question 31

Briefly define bipolar disease

Answer 31

Symptoms of major depression and mania/hypomania Bipolar I = more mania +extreme mood swings, very euphoric then very depressed Bipolar II = recurrent depressive episodes + hypomanic episodes +less extreme on positive side, still very sad

Question 32

List three classes of drugs (inc. examples) used for tx of bipolar disease

Answer 32

Lithium = 1st line Antiseizure drugs +valproic acid +carbamazepine +lamotrigine ``` 2nd gen antipsychotics +ziprasidone +olanzapine +risperidone +aripiprazole +quetiapine ```

Question 33

For lithium, describe clinical uses and major side effects and contraindications

Answer 33

Indications: bipolar disease AEs = "L..M..N..O..P" - movement problems - tremor - nephrogenic DI - hypOthyroidism - Pregnancy NO! - N/V - kidney dysfunction CI - pregnancy - renal disease - thyroid dysfunction

Question 34

What are AEs of 1st generation antipsychotics? | From D2 receptor blockade

Answer 34

``` Extrapyramidal Sx's (EPS) Acute = -dystonia -akathisia -Parkinsonian syndrome ``` Late EPS = tardive dyskinesia Neuroleptic malignant syndrome (rare) Hyperprolactinemia

Question 35

How do you treat acute extrapyramidal symptoms from 1st generation antipsychotics?

Answer 35

Dec. dose Change to a 2nd gen. Administer muscarinic receptor antagonist = trihexyphenidyl Change to a lower potency antipsychotic

Question 36

What are differences amongst 1st generation antipsychotics and their potencies?

Answer 36

Low potency = more blockade of H1, M, alpha1 High potency = more extrapyramidal effects

Question 37

What are AEs of 1st generation antipsychotics? | Due to M, alpha1 and H1 blockade

Answer 37

M blockade = Anticholinergic: dry mouth, blurred vision, urinary retention, constipation alpha1 blockade = orthostatic hypotension H1 blockade = sedation, inc. weight and appetite

Question 38

What is the MOA of second generation antipsychotics?

Answer 38

D2 receptor blockade 5HT2A receptor blockade

Question 39

What are indications for 2nd generation antipsychotics?

Answer 39

Schizophrenia - more effective against negative symptoms compared to 1st gen. Antipsychotics

Question 40

What are AEs of 2nd generation antipsychotics?

Answer 40

Dec. risk of EPS Can cause metabolic syndrome

Question 41

What are the high potency first generation antipsychotics?

Answer 41

"Try to Fly High" Trifluperazine Fluphenazine Haloperidol