Antipsychotics

Question 1

psychosis definition

Answer 1

denotes a variety of mental disorders with multiple causes and manifestations
-systemic, psychiatric or chemical (toxic)

Question 2

what is a characteristic of severe psychiatric disorders?

Answer 2

disturbances in behavior or thought processing

• delusions (false beliefs)
• various types of hallucinations (auditory, visual, tactile, olfactory)

Question 3

Schizophrenia

• what is it?
• when does it develop?

Answer 3

• severe type of psychosis

- develops during childhood and adolescence == genetic disorder with high heritability

Question 4

typical antipsychotics - list drugs?

Answer 4

Chlorpromazine
thioridazine
fluphenazine
haloperidol

Question 5

2 Types of symptoms in schizophrenia:

Answer 5

• positive

- negative

Question 6

Positive schizophrenia symptoms:

Answer 6

-Manifestation of abnormal beh:
delusions
hallucinations (auditory)
agitation
paranoia
aberrant thinking
intrusion of thoughts

Question 7

Negative schizophrenia symptoms:

Answer 7

-Absence of normal beh:
emotional apathy (flat affect)
socially withdrawn
inattentiveness

Question 8

Schizophrenia- pathophysiology:

Answer 8

dopamine hypothesis among many others:

hyperactivity of the mesolimbic/mesocortical DA system = excessive limbic DA activity = psychosis

Question 9

Atypical antipsychotics - list the drugs we need to know:

Answer 9

clozapine
olanzapine
risperidone
aripiprazole
quetiapine
ziprasidone

Question 10

What are neuroleptic drugs?

Answer 10

subtype of antipsychotic drugs that produce high incidence of extrapyramidal side effects (EPS)

Question 11

Why are atypical antipsychotics more widely used?

Answer 11

These are the NEWER drugs (typical are old ones)

These have fewer EPS effects at equivalent therapeutic doses

Question 12

Uses for antipsychotic agents:

Answer 12

1) schizophrenia
2) psychotic beh
a) psychotic bipolar disorder
b) psychotic depression
c) Tx-resistant depression
3) severe mania - manic phase of bipolar disorder
4) antiemetic (prochlorperazine, phenergan)

Question 13

Phenothiazines -Aliphatic (R1)

What is the potency of…
= chlorpromazine

Answer 13

LEAST POTENT

Question 14

Phenothiazines -Piperidine (R1)

What is the potency of…
=thioridazine

Answer 14

MEDIUM POTENT

Question 15

Phenothiazines -Piperazine (R1)

What is the potency of…
=prochlorperazine
=fluphenazine

Answer 15

HIGHEST POTENCY

Question 16

Butyrophenol drug name and potency?

Answer 16

haloperidol

HIGHEST HIGHEST POTENCY (even higher than pipierazines)

Question 17

Name the dibenzapines?

Answer 17

• clozapine

- olanzapine

Question 18

Name the benzisoxazoles:

Answer 18

-risperidone

Question 19

Name the other atypical antipsychotics?

Answer 19

aripiprazole
quetiapine
ziprasidone

Question 20

antipsychotics - general pharmacokinetics:

Answer 20

• low bioavailability - Lipophilic drugs
• large Vd
• metabolized by liver

Question 21

*Antipsychotics - what is special about typical and atypical agent metabolism?

Answer 21

• typical- the metabolites ARE NOT active after going through liver
• -atypical-the metabolites are significantly activated when going through CYP450

Question 22

Typical antipsychotic drugs -MOA?

Answer 22

dopamine receptor antagonist - D2 recepotrs!!

Question 23

Atypical antipsychotic drugs- MOA?

Answer 23

antagonist at 5-HT_2A receptors and D2 receptors

Question 24

Primary action of antipsychotic drugs?

Answer 24

-Meso-limbic-mesocortical

• VTA (ventral tegmental area)–>limbic system & neocortex
• related to behavior and psychosis

Question 25

Other actions of antipsychotic drugs?

Answer 25

1) Nigrostriatal-
a) Substantia nigra–>dorsal striatum
b) coordination of voluntary movement
c) blcokage of D2 receptor responsible for EPS
2) Tuberoinfundibular - inh of prolactin secretion from ant pituitary
3) Medullary periventricular area
a) chemoreceptor trigger zone (CTZ)
b) eating behavior

Question 26

Antidopaminergic effects of Antipsychotics:

Answer 26

1) cognitive function (antipsychotic) - more effective with positive symptoms than neg
2) Motor behavior (EPS)
a) parkinson like syndrome: rigidity, tremor, bradykinesia
b) Akathesia -motor restlessness and anxiety
c) Dystonia
- torticollis-spasm of neck
- episthotonus-spasm of back
- oculogyric reaction-eyes roll back
- facial grimacing
d) Tardive dyskinesia
- involuntary movements of tongue, mouth, face and head
- generally irreversible
3) Nausea & vomiting (antiemetic)
a) effective in drug induced conditions (cancer chemo)
b) not effective in motion sickness
c) thioridazine is a poor antiemetic
* 4) endocrine - hyperprolactinemia
a) decreased testosterone production (male)
b) gynecomastia (male)
c) changes in libido, impotence and infertility (male)
d) galactorrhea and infertility (female)
e) menstrual irregularities
5) Weight gain
a) DA, or H1 mechanism, maybe also 5-HT
b) Clozapine and olanzapine

Question 27

Which class and which drugs typically have WG as side effect?

Answer 27

Atypicals usually

Clozapine and olazapine

Question 28

Pharmacological effects/which receptors - antipsychotics?

Answer 28

1) anticholinergic (M-receptors)
- urinary retention
- dry mouth
- blurred vission
- constipation
- mental confusion
2) Antihistaminic (H1)
- sedation
- WG
3) Anti-adrenergic (most alpha1)
- postural hypotension
- reflex tachycardia
- erectile dysfunction and impaired ejaculation

Question 29

Adverse effects of antipsychotics?

Answer 29

1) DA-mediated
a) EPS effects
- parkinsonian-like
- akathesia
- dystonia
- tardive dyskinesia
b) hypoprolactinemia
c) neuroleptic malignant syndrome
- hypertension & hyperthermia
- rare though significant mortality
- treatment=supportive, dantrolene, diazepam, bromocriptine
2) Anticholinergic
3) Antiadrenergic
4) Antihistaminic
5) WG - inc risk for Type2Diabetes; metabolic syndrome

Question 30

WHcih class has lower EPS symptoms?

Answer 30

the atypicals

Question 31

Which atypical is most strongly associated with EPS?

Answer 31

risperidone

Question 32

Which atypicals least strongly associated with EPS?

Answer 32

clozapine

quetiapine

Question 33

EPS risk is influenced by?

Answer 33

• rapid dose escalation
• target dose (concentration/receptor occupancy)
• patient vulnerability

Question 34

Tardive dyskinesia affects what age population most?

Answer 34

the elderly