AntiPsychotics

Question 1

Dopamine pathways

Answer 1

Mesolimbic pathway
Mesocortical pathway
Nigrostriatal pathway
Tuberoinfundibular pathway

Question 2

Mesolimbic pathway

Answer 2

which is thought to be hyperactive in schizophrenia and to mediate positive symptoms of psychosis such as delusions and hallucinations, from Vta to Nac

Question 3

Mesocortical pathway

Answer 3

which is thought to be underactive in schizophrenia and thus mediate negative psychotic symptoms such as loss of motivation and social withdrawal, from Vta to PFC.

Question 4

Nigrostriatal pathway

Answer 4

Which is part of the extrapyramidal nervous system and controls motor functions and movements. Deficiency of dopamine in this pathway can lead to dystonia and parkinsonism disease symptoms, while excess of dopamine can lead to hyperkinetic movements such as tics and dyskinesias, From substantia nigra to basal ganglia.

Question 5

Tuberoinfundibular pathway

Answer 5

Which controls prolactin secretion specifically dopamine in this pathway inhibits prolactin release and as a reminder prolactin is a hormone that enables milk production and is also involved in the control of sexual desire and regulation of the immune symptom. From hypothalamus arcuate nucleus to the hypothalamus median eminence.

Question 6

Forms of psychosis

Answer 6

1. Simple
2. Catatonic
3. Hebephrenic 4. Paranoid
4. Residual

Question 7

1st. generation typical antipsychotics: (classical neuroleptics)
EXAMPLES

Answer 7

Chlorpromazine Fluphenazine Thioridazine Thiothixene Haloperidol

Question 7

1st. generation typical antipsychotics: (classical neuroleptics)
EXAMPLES

Answer 7

Chlorpromazine
Fluphenazine 
Thioridazine 
Thiothixene 
Haloperidol 
PROCHLORPERAZINE 
TRIFLUOPERAZINE

Question 8

1st. generation typical antipsychotics: (classical neuroleptics)
MOA

Answer 8

● competitive blockade of dopamine D2 receptors on postsynaptic neurons. also blocks alpha receptors, cholinergic receptors and histamine receptors
● First-generation antipsychotics are more likely to be associated with movement disorders
– > known as extrapyramidal symptoms (EPS)
● EPS = Dystonia, Akathisia, pseudoparkinsonism, tardive dyskinesia
● Less likely to have any metabolic abnormalities.
● not selective for any of the four dopamine pathways

Question 9

1st. generation typical antipsychotics: (classical neuroleptics)

SIDE EFFECTS

Answer 9

EPS symptoms 
Hyperprolactinemia
sedation 
weight gain 
ABCDs 
hypotension

Question 10

1st. generation typical antipsychotics: (classical neuroleptics)
CONTRAINDICATIONS

Answer 10

Hypersensitivity
Parkinsons
Dementia w/ Lewy bodies
Drinking

Question 11

2nd generation atypical antipsychotics (atypical neuroleptics)

EXAMPLES

Answer 11

CLOZAPINE
OLANZAPINE
QUETIAPINE
RISPERIDONE

Question 12

2nd generation atypical antipsychotics (atypical neuroleptics)
USE

Answer 12

Schizo pos. symptoms and neg.

symptoms (Mesocortical)

Question 13

2nd generation atypical antipsychotics (atypical neuroleptics)
MOA

Answer 13

blocks D2 activity and 5HT-2a on postsynaptic neurons. also blocks alpha receptors, cholinergic receptors and histamine receptors

Question 14

2nd generation atypical antipsychotics (atypical neuroleptics)

SIDE EFFECTS

Answer 14

EPS
prolactin levels 
increased weight gain sedation hyperglycemia 
hypotension 
Agranulocytosis

Question 15

2nd generation atypical antipsychotics (atypical neuroleptics)
CONTRAINDCATION

Answer 15

Hypersensitivity Myeloproliferative disorders

Epilepsy

Question 16

BUPROPION

MOA

Answer 16

Inhibits DA and NE reuptake. SE: Tachycardia and insomnia.

Question 17

MIRTAZAPINE

Answer 17

α2 antagonist, increased NE & serotonin release. H1 antagonist. SE: Sedation, increased appetite and increased weight.

Question 18

TRAZODONE

Answer 18

Blocks serotonin receptors, α1, H1 and Serotonin reuptake. SE: Sedation, priapism.

Question 19

VARENICLINE

Answer 19

Nicotinic partial agonist, used for smoking cessation.

Question 20

VILAZODONE

Answer 20

inhibits serotonin reuptake and serotonin partial agonist.

Question 21

1st. generation typical antipsychotics: (classical neuroleptics)
USES

Answer 21

● Schizophrenia
● Bipolar disorder (manic phase)
● Antiemesis
● Preop sedation

Question 22

Phenothiazines

EXAMPLES

Answer 22

Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene

Question 23

Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene

MOA

Answer 23

● Blocks D2 receptor

● Also blocks alpha, muscarinic, and H1 receptors

Question 24

Chlorpromazine Fluphenazine Thioridazine Thioxanthene USE

Answer 24

● Schizophrenia ● Bipolar disorder (manic phase) ● Antiemesis ● Preop sedation

Question 25

Chlorpromazine Fluphenazine Thioridazine Thioxanthene ADVERSE EFFECTS

Answer 25

● Extensions of alpha and muscarinic receptor blocking action. ● Extrapyramidal dysfunctions ( Dystonia, Akathisia, pseudoparkinsonism, tardive dyskinesia) ● Hyperprolactinemia

Question 26

What type of drug is haloperidol

Answer 26

Butyrophenone

Question 27

Haloperidol | MOA

Answer 27

● Blocks D2 receptors ● Blocks few alpha receptors compared to phenothiazines ● Blocks few muscarinic receptors compared to phenothiazines ● Less sedation compared to phenothiazines

Question 28

Haloperidol | USE

Answer 28

● Schizophrenia ● Bipolar disorder (manic phase) ● Huntington’s chorea ● Tourette syndrome

Question 29

Haloperidol | SIDE EFFECT

Answer 29

● Extrapyramidal dysfunction (Dystonia, Akathisia, pseudoparkinsonism, tardive dyskinesia)

Question 30

list the atypical neuroleptics

Answer 30

``` Aripiprazole Brexpiprazole Clozapine ( note most important side effect - agranulocytosis ) Olanzapine Quetiapine Risperidone Ziprasidone ```

Question 31

Aripiprazole | MOA

Answer 31

● partial agonists at D2 and 5-HT1A receptors, as well as antagonists of 5-HT2A receptors. ● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery ● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

Question 32

Brexpiprazole: MOA

Answer 32

● Newer 2nd gen drugs ● partial agonists at D2 and 5-HT1A receptors, as well as antagonists of 5-HT2A receptors ● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery ● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

Question 33

MOST IMPORTANT SIDE EFFECT OF CLOZAPINE

Answer 33

agranulocytosis

Question 34

Clozapine | MOA

Answer 34

● high affinity for D1, D4, 5-HT2, muscarinic, and α-adrenergic ● Weak D2 receptor antagonist ● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery ● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

Question 35

Olanzapine | MOA

Answer 35

● blocks 5-HT2A receptors to a greater extent than it does D2 receptors ● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery ● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

Question 36

Quetiapine MOA & SEs

Answer 36

relatively weak at blockade of D2 and 5-HT2A receptors ● low risk for EPS ``` Side effects: ● dizziness, feeling unsteady, or having trouble keeping your balance. ● pain in the joints, back, neck, or ears. ● weakness. ● dry mouth. ● vomiting. ● indigestion. ● constipation. ```

Question 37

Risperidone MOA

Answer 37

blocks 5-HT2A receptors to a greater extent than it does D2 receptors

Question 38

Clinical applications of atypical neuroleptics (1)

Answer 38

Actions: ● The clinical effects of antipsychotic drugs reflect a blockade at dopamine and/or serotonin receptors ● They also block cholinergic, adrenergic, and histaminergic receptors 1. Antipsychotic effects: ● reduce hallucinations and delusions associated with schizophrenia (known as “positive” symptoms) by blocking D2 receptors in the mesolimbic system of the brain ● Many second-generation agents, such as clozapine, can reduce the negative symptoms to some extent. 2. Extrapyramidal effects: ● Dystonias, Parkinson-like symptoms, akathisia, and tardive dyskinesia can occur with both acute and chronic treatment ● The second-generation antipsychotics exhibit a lower incidence of EPS.

Question 39

Clinical applications of atypical neuroleptics (2)

Answer 39

3. Antiemetic effects: ● The antipsychotic drugs have antiemetic effects that are mediated by blocking D2 receptors of the chemoreceptor trigger zone of the medulla 4. Anticholinergic effects: ● Some of the antipsychotics, particularly thioridazine, chlorpromazine, clozapine, and olanzapine, produce anticholinergic effects. ● The anticholinergic effects may actually assist in reducing the risk of EPS with these agents. 5. Other effects: ● Blockade of α-adrenergic receptors causes orthostatic hypotension and light-headedness. ● alter temperature-regulating mechanisms and can produce poikilothermia ● In the pituitary, antipsychotics that block D2 receptors may cause an increase in prolactin release. ● Sedation ● Sexual dysfunction

Question 40

USE of atypical neuroleptics

Answer 40

● Schizophrenia (positive and negative symptoms) ● Bipolar disorder ● Major depression ● Agitation (seen in alzheimers and parkinsons) ● Prevention of nausea and vomiting ● treat intractable hiccups ● treatment of the motor and phonic tics of Tourette disorder ● tic disorder ● management of disruptive behavior and irritability secondary to autism.

Question 41

Side effects of atypical neuroleptics

Answer 41

``` ● Urinary retention ● Weight gain (clozapine, olanzapine) ● Seizure ● Sedation ● Extrapyramidal symptoms ● Postural hypotension ● Sexual dysfunction ● Arrhythmias ● Sudden cardiac death ● Dry mouth ● Agranulocytosis (clozapine) ● Diabetes (clozapine, olanzapine) ● Hyperprolactinemia (risperidone) ● Qt prolongation (ziprasidone) ● Tardive dyskinesia ● Neuroleptic malignant syndrome ```