Watts Schizo

Question 1

Etiology of schizophrenia

Answer 1

-Neurodevelopmental/anatomical
-Genetics-neuronal growth, migration of neurons
-Environmental-birth complications, infections
-Gene-environment interaction
-Neurodevelopment-environment interaction

Question 2

What are positive symptoms of schizophrenia?

Answer 2

-Respond well to drug therapy
-Hallucinations
-Delusions
-Bizarre behavior
-Thought disorder

Question 3

What are negative symptoms of schizophrenia?

Answer 3

-Little response to drug therapy, newer agents are better
-Blunted emotion
-Poor self-care
-Social withdrawal
-Poverty in speech

Question 4

What are the receptors antagonized by antipsychotics?

Answer 4

-Dopamine
-Serotonin
-Norepinephrine
-Acetylcholine
-Histamine

Question 5

What is the major receptor antagonized by antipsychotics?

Answer 5

Dopamine

Question 6

What is the newer receptor antagonized by antipsychotics?

Answer 6

Serotonin

Question 7

What has more predictable dosing, D2 or D1?

Answer 7

D2

Question 8

Actions of D2 antagonists on the basal ganglia (nigrostriatal pathway)

Answer 8

-Motor effects
-Extrapyramidal symptoms

Question 9

Actions of D2 antagonists on the mesolimbic

Answer 9

Primary therapeutic effects

Question 10

Actions of D2 antagonists on the mesocortical

Answer 10

-Hypofunction in schizophrenia
-Antagonists may exacerbate cognitive deficits

Question 11

Actions of D2 antagonists on the Hypothalamus and endocrine systems

Answer 11

D2 receptor blockade in endocrine system

Question 12

Actions of D2 antagonists on the medulla

Answer 12

-Chemoreceptor trigger zone
-D2 antagonists are anti-emetics

Question 13

Drug-induced movement disorders (D2 antagonism)

Answer 13

-Extrapyramidal symptoms (EPS) (30-50%)
-Tardive dyskinesia (20-40%)
-Neuroleptic malignant syndrome (NMS)

Question 14

When do extrapyramidal symptoms appear?

Answer 14

Occur early, days/weeks, reversible

Question 15

What are the extrapyramidal symptoms?

Answer 15

-Dystonia - increased muscle tone
-Pseudoparkinsonism - muscle rigidity
-Tremor
-Akathisia - restlessness

Question 16

Drug therapy for EPS

Answer 16

-Anticholinergic agents
-Antihistamines
-Dopamine-releasing agents
-Used for akathisia

Question 17

When does tardive dyskinesia appear

Answer 17

Occur late, months to a year, IRREVERSIBLE

Question 18

Symptoms of tardive dyskinesia

Answer 18

-Mouth - rhythmic involuntary movements
-Choreiform - irregular purposelessness
-Athetoid - worm-like
-Axial hyperkinesias - “to-and-fro” movements

Question 19

Monitoring of tardive dyskinesia

Answer 19

AIMS (abnormal involuntary movement scale) rating scale; check every 6 months

Question 20

Treatment of tardive dyskinesia

Answer 20

-Prevention! Use the least risky agent at the lowest dose possible and monitor
-Reduce dose of current agent
-Change to a different drug; possibly a newer agent
-Eliminate anticholinergic drugs
-VMAT inhibitors

Question 21

What are the VMAT inhibitors for tardive dyskinesia

Answer 21

-Tetrabenazine (Xenazine) for Huntington’s chorea
-Valbenazine (Ingrezza) for TD
-Deutetrabenazine (Austedo) for TD and Huntington’s chorea

Question 22

When does neuroleptic malignant syndrome appear?

Answer 22

Immediately and serious; 10% fatality

Question 23

What are the symptoms of neuroleptic malignant syndrome?

Answer 23

-EPS symptoms with fever
-Impaired cognition - agitation, delirium, coma
-Muscle rigidity

Question 24

Treatment of neuroleptic malignant syndrome

Answer 24

-Restore dopamine balance
-Discontinue drug
-DA agonists, diazepam, or dantrolene (skeletal muscle relaxant)

Question 25

How long does it take for antipsychotic drugs to take effect when treating psychosis?

Answer 25

-2-3 weeks for effectiveness -6 weeks to 6 months maximal efficacy

Question 26

Pharmacological effects of the antipsychotic drugs

Answer 26

-Behavioral effects: Unpleasant in normal subjects or reversal of signs and symptoms of psychosis in affected individual -"Neuroleptic" syndrome: Suppress emotions, reduce initiative and interest, affect; may resemble negative symptoms -Block conditioned avoidance responses in animal studies -Decreased spontaneous activity, aggressive, and impulsive behavior

Question 27

Manifestations associated with muscarinic cholinoreceptor blockade

Answer 27

-Loss of accommodation -Dry mouth -Difficulty urinating -Constipation

Question 28

Manifestations associated with alpha adrenoreceptor blockade

Answer 28

-Orthostatic hypotension -Impotence -Failure to ejaculate

Question 29

Manifestations associated with dopamine receptor blockade

Answer 29

-Parkinson's syndrome -Akathisia -Dystonias

Question 30

Manifestations associated with supersensitivity of dopamine receptors

Answer 30

Tardive dyskinesia

Question 31

Manifestations associated with muscarinic blockade

Answer 31

Toxic-confusional state

Question 32

Manifestations associated with histamine receptor blockade

Answer 32

Sedation

Question 33

Manifestations associated with dopamine receptor blockade resulting in hyperprolactinemia

Answer 33

-Amenorrhea-galactorrhea -Infertility -Impotence

Question 34

Manifestations associated with combined histamine and serotonin blockade

Answer 34

Weight gain

Question 35

Precautions/contraindications associated with antipsychotic drugs

Answer 35

-Cardiovascular (hypotension and QT interval prolongation) -Parkinsons disease -Epilepsy (clozapine will lower seizure threshold) -Diabetes (contraindicated for newer agents)

Question 36

What does a drug that has high serotonin/dopamine ratio cause?

Answer 36

EPS

Question 37

What are the aliphatic phenothiazines?

Answer 37

-Chlorpromazine (Thorazine) - no longer first-line therapy -Promethazine (Phenergan) - more likely to be used for N/V

Question 38

Which aliphatic phenothiazine is more likely to be used for H1 antagonist properties?

Answer 38

Promethazine

Question 39

What are the piperidine phenothiazines?

Answer 39

Thioridazine (Mellaril) - sedation, hypotension; anticholinergic, many SE

Question 40

What are the piperazine phenothiazines?

Answer 40

-Fluphenazine (Permtil, Prolixin) - EPS -Prochlorperazine (Compazine) - antiemetic -Perphenazine (Trilafon) - just as effective as newer agents

Question 41

What are the thioxanthines?

Answer 41

-Thiothizene (Navane) - modest EPS

Question 42

What are the butyrophenones?

Answer 42

-Haloperidol (Haldol) - EPS

Question 43

Miscellaneous antipsychotics

Answer 43

-Molindone (Moban) - moderate EPS -Pimozide (Orap) - Tourette's disease-tics, vocalizations

Question 44

Key points of chlorpromazine (Thorazine)

Answer 44

-First antipsychotic -Antihistamine side effects

Question 45

Key points of promethazine (Phenergan)

Answer 45

-Antihistamine -Antiemetic

Question 46

Key points of thioridazine (Mellaril)

Answer 46

-Many side effects: anticholinergic, sexual dysfunction, cardiovascular

Question 47

Key points of perphenazine (Trilafon)

Answer 47

CATIE studies: combination with anticholinergic

Question 48

Key points of thiothixene (Navane)

Answer 48

Modest EPS

Question 49

Key points of haloperidol (Haldol)

Answer 49

EPS

Question 50

Key points of molindone (Moban)

Answer 50

Moderate EPS

Question 51

Key points of pimozide (Orap)

Answer 51

Tourette's disease, suppress motor and vocal tics

Question 52

Atypical/second generation antipsychotics

Answer 52

-Clozapine -Olanzapine -Loxapine -Quetiapine -Risperidone -Paliperidone -Iloperidone -Ziprasidone -Asenapine -Lurasidone -Pimavanserin -Aripiprazole

Question 53

D2/D3 partial agonists

Answer 53

-Brexpiprazole -Cariprazine -Lumateperone

Question 54

Clozapine key points

Answer 54

-First atypical antipsychotic -Agranulocytosis -Risk of diabetes -Superior efficacy

Question 55

Olanzapine key points

Answer 55

-Weight gain -Risk of diabetes

Question 56

Quetiapine key points

Answer 56

-Metabolite with antidepressant activity -Hypotension -Sedation

Question 57

Risperidone key points

Answer 57

-Serotonin/dopamine receptor antagonist

Question 58

Ziprasidone key points

Answer 58

-Serotonin/dopamine, alpha 1 affinity -prolongs QT interval

Question 59

Lurasidone key points

Answer 59

-Serotonin/dopamine receptor affinity -Reduced metabolic effects -Rapid titration

Question 60

Aripiprazole key points

Answer 60

-High serotonin/dopamine receptor affinity -Partial agonist activity

Question 61

Drugs in development/under investigation

Answer 61

Dual M1/M4 muscarinic agonist combined with peripheral muscarinic antagonist (KarXT)