Antipsychotics- Gulsevin

Question 1

What is psychosis?

Answer 1

collection of symptoms that lead to loss of contact with reality: hallucinations, delusions, disordered thinking. typically we see this with pt with schizophrenia, BPD, and possibly Parkinson’s, Alzheimer’s, or age related dementia

Question 2

What are the positive symptoms of schizophrenia?

Answer 2

-hallucinations
-delusions
-disorganized speech
-disorganized behavior

Question 3

What are the negative symptoms of schizophrenia?

Answer 3

-social withdrawal
-blunted affect
-poverty of speech
-lack of energy and motivation
-anhedonia (lack of enjoyment/pleasure in life)
-cognitive problems

Question 4

What are the symptoms of mania in BPD?

Answer 4

-racing thought
-inflated self-esteem
-feeling of euphoria
engagement of risk behavior
-reduced need to eat/sleep
-delusions/hallucinations

Question 5

What are the symptoms of depression in BPD?

Answer 5

-difficulty concentrating or making decisions
-low self esteem
-low mood
-loss of interest of activities
-inability to eat or sleep or excessive sleeping
-anxiety/hopelessness/suicidal thoughts

Question 6

How are antipsychotic used for schizophrenia treatment?

Answer 6

used for relief of positive symptoms

Question 7

What are the classes of first generation antipsychotics?

Answer 7

-phenothiazine
-thioxanthene
- butyrophenone

Question 8

What is the Dopamine Hypothesis of Schizophrenia?

Answer 8

positive symptoms result from hyperactivity of mesolimbic dopamine

Question 9

What is the overall MOA of first generation of antipsychotics?

Answer 9

inhibit dopamine neurotransmission (typically at D2 receptors)

Question 10

What are the side effects of phenothiazine derivatives?

Answer 10

neuroleptic symptoms (labile blood pressure, tachypnea, tachycardia, sialorrhea, diaphoresis, flushing, skin pallor, and incontinence)

Question 11

What is the cause of Extrapyramidal Symptoms?

Answer 11

deficiency of dopamine in nigrostriatal DA pathway

Question 12

What is the cause of Tardive Dyskinesia?

Answer 12

chronic D2 blockade in nigrostriatal DA pathway

Question 13

What are the adverse effects of typical antipsychotics?

Answer 13

-muscarinic antagonist activity= anticholinergic SE (dry mouth, constipation, blurred vision, increased HR)
-histamine (H1) activity= sedation, weight gain
-alpha1 antagonist activity= hypotension, sedation

Question 14

What is the most potent first gen antipsychotic?

Answer 14

haloperidol

Question 15

State the potency of first gen antipsychotics from least to most potent

Answer 15

lowest= thioridazine
-prochlorperazine
-loxapine
-perphenazine
-thiothixene
-trifluoperazine
-pimozide
-fluphenazine
highest= haloperidol

Question 16

What first gen antipsychotics can be used to treat schizophrenia?

Answer 16

-all phenothiazines derivatives (chlorpromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine)
-all thioxanthene derivatives (thiothixene, thioproperazine)
-haloperidol
-pimozide
-loxapine -> amoxapine (tricyclic antidepressant metabolite)

Question 17

What first gen antipsychotics can be used for BPD?

Answer 17

-all phenothiazines derivatives (chlorpromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine)
-all thioxanthene derivatives (thiothixene, thioproperazine)
-haloperidol
-pimozide
-loxapine -> amoxapine (tricyclic antidepressant metabolite)

Question 18

What first gen antipsychotics can be used for Tourette’s Syndrome?

Answer 18

butyrophenones
-haloperidol
-pimozide

Question 19

What first gen antipsychotic can be used for N/V associated with surgical procedures?

Answer 19

droperidol (butyrophenone)

Question 20

What makes an antipsychotic atypical?

Answer 20

doesn’t bind D2 receptors as well as “typical” antipsychotics and binds well to 5-HT2A receptors (although typical antipsychotics may also do this)

Question 21

What is the general theory of second gen antipsychotics (atypical)?

Answer 21

5HT2A antagonist activity along with D2 antagonist activity, serotonin modulates dopamine differently depending on the area of the brain

Question 22

What is the result of blocking 5-HT2A receptors in the mesolimbic dopamine pathway?

Answer 22

blocking 5HT2A does not interfere with dopamine antagonism= D2 blockade improves positive symptoms

Question 23

What is the result of blocking 5-HT2A receptors in the mesocortical tract?

Answer 23

blocking 5HT increases dopamine release= improves negative symptoms

Question 24

What is the result of blocking 5-HT2A receptors in the nigrostriatal dopamine pathway?

Answer 24

blocking 5HT2A receptors increases dopamine release which competes with D2 antagonist and less blockade= improved EPS and tardive dyskinesia symptoms

Question 25

What drugs are 6-7-6 tricyclic atypical antipsychotics?

Answer 25

-clozapine
-olanzapine
-quetiapine
-asenapine

Question 26

What are unique characteristics of Asenapine (6-7-6 atypical antipsychotic)?

Answer 26

-fewer muscarinic side effects
-oral delivery not possible due to extensive glucuronidation in the liver, so formulated as sublingual tab or transdermal patch
-should NOT be used with strong CYP1A2 and CYP2D6 inhibitors

Question 27

What drug is a selective 5HT2 antagonist that can be given in combo with Haloperidol to decrease EPS symptoms?

Answer 27

ritanserin

Question 28

What are the indications of Risperidone?

Answer 28

schizophrenia, BPD, and irritability associated with autistic disorder

Question 29

What is the MOA of Risperdone?

Answer 29

D2 and 5HT2A antagonist

Question 30

What are the preparations of Risperidone?

Answer 30

oral tab, solution, disintegrating tab, powder for IM injection (IM DOA= 2-4 weeks -> paliperidone (active metabolite))

Question 31

What are the rare but serious side effects of Iloperidone?

Answer 31

stoke and QT prolongation

Question 32

What are the side effects of Quetiapine?

Answer 32

QT prolongation, muscarinic side effects, sedation (but is seen as a positive for schizophrenic and BPD pt with insomnia and anxiety)

Question 33

What is the MOA of Ziprasidone and what makes that unique?

Answer 33

D2, 5HT2A, and D3 antagonist but 5HT1A agonist which possesses anxiolytic effects that can improve cognition and working memory

Question 34

What are the characteristics of third gen antipsychotics?

Answer 34

-D2 partial agonist + serotonin effects
-longer t1/2 lives

Question 35

What is the use of third gen antipsychotic, Aripiprazole?

Answer 35

adjunctive treatment for schizophrenia, BPD, and MMD

Question 36

What drugs are adjunctive treatment for schizophrenia, BPD, and MDD?

Answer 36

aripiprazole, bexipiprazole, and cariprazine