CHAPTER 11: ANTIPSYCHOTIC DRUGS

Question 1

psychotic disorders are? two main symptoms?

Answer 1

severe mental disorders that cause ABNORMAL thinking and perception, lose touch with reality

TWO MAIN SYMPTOMS= delusions (false beliefs) and hallucinations (false perceptions)

Question 2

schizophrenia

Answer 2

• type of chronic psychosis
• strong genetic component (combo fo genes play a role in the psychosis)
  -biochem abnormality, dysfunc of mesocortical or limbic dopaminergic neuronal pathways

Question 3

pos vs neg symptoms

Answer 3

hyperreaction=pos
underreaction of pathways=neg symptoms

Question 4

dopamine (DA) hypothesis

Answer 4

changes in dopamine causes unusual behavior and experiences associate with psychosis

Question 5

4 TYPES OF DOPAMINERGIC PATHWAYS IN THE BRAIN

Answer 5

Nigrostriatal, mesocortical, mesolimbic, tuberoinfundibular

Question 6

Nigrostriatal Pathway

Answer 6

• control motor func
• deficiency DA leads to parkinson like symptoms
• excess DA lead to hyperkinetic movement

Question 7

Mesocortical Pathway

Answer 7

underactive, mediate negative symptoms

Question 8

Mesolimbic Pathway

Answer 8

Hyperactive in schizophrenia
- mediate positive symptoms

Question 9

Tuberoinfundibular Pathway

Answer 9

control prolactin secretion

Question 10

FIRST GEN AGENTS
- 2 types depend on what?

Answer 10

first gen–> split into low potency or high potency depending on affinity for DOPAMINE D2 RECEPTOR

Question 11

First Gen Antipsychotics- CONVENTIONAL

Answer 11

• competitive inhibitors (d1-d5 receptors)
• competitive D2 blockade cause antipsychotic effects
• EPS: extrapyramidal symptoms depend on binding affinity

Question 12

EPS- extrapyramidal symptoms

Answer 12

• symptoms due to dysfunction of movement
• dystonia, tardive dyskinesia

EX) Haloperidol binds tightly, chlorpromazine binds less tightly

Question 13

Second Gen Antipsychotics- ATYPICAL

Answer 13

first-line therapy

• LOWER incidence of EPS
• HIGHER risk metabolic adv effects (diabetes, hypercholesterolemia, weight gain)
• BLOCKADE 5HT (serotonin) and DA receptors

Question 14

ALL FIRST GEN/ SOME SECOND- MOA

Answer 14

• BLOCK D2 dopamine rec in brain and periphery
  on POST synaptic membrane

Question 15

MOST SECOND GEN- MOA

Answer 15

• additional action through inhibition of serotonin 5-HT receptors
• 5-HT2a receptors
• acting on serotonin receptors shows therapeutic effects

Question 16

DRUG ACTIONS- other receptors blocked?

Answer 16

• cholinergic, adrenergic, histaminergic
• unknown if these alleviate psychosis symptoms
• may cause undesirable effects

Question 17

ANTIPSYCHOTIC EFFECTS
- pos and neg symptoms

Answer 17

POSITIVE:
- reduce hallucinations/delusions–> block mesolimbic D2

NEGATIVE
- blunted affect, apathy, attention, cognitive impairment–> not as responsive, especially 1st gen

2nd gen may alleviate neg symptoms

Question 18

EXTRAPYRAMIDAL EFFECTS

Answer 18

• dystonias (twitching muscles)
• Parkinson like symp (bradykinesia, tremor, rigidity)
• akathisia (motor restlessness)
• tardive dyskinesia (involun movements)–> ex) tongue/fly catching movement

2nd gen lower EPS incidence

Question 19

ANTIEMETIC EFFECTS

Answer 19

• mediated by blocking D2 of chemoreceptor trigger zone of medulla
  (once stimulated causes nausea/vomiting)

Question 20

ANTICHOLINERGIC EFFECTS

Answer 20

• thioridazine, chlorpromazine, clozapine, olanzapine
• blurred vision, dry mouth, confusion, inhibition GI/urinary tract smooth muscle

Question 21

OTHER EFFECTS

Answer 21

• inhibition alpha adrenergic–> orthostat hypo, syncope/dizzy
• block D2 in pituitary–> inc prolactin (blocking tuberoinfun)
• block H1 histamine rec–> sedation
  ( chlorpromazine, olanzapine, quetiapine, clozapine)
• sexual dysnfunc/weight gain

Question 22

THERAPEUTIC USES

Answer 22

-schizophrenia (1st gen best)
- manic symptoms/bipolar (lurasidone, quetiapine)
- drug induced nausea/vomit (prochlorperazine)
- tic disorder (pimozide, risperidone, haloperidol)
- refractory depression (no adequate response to treatment)–> (aripiprazole, brexpiprazole, quetiapine)
- intractable hiccups (chlorpromazine)

Question 23

ADVERSE EFFECTS- Extrapyramidal

Answer 23

• dystonias (few hrs of treatment)
• akathisias (days to weeks)
• PD like symptoms (weeks to months)
• Tardive dyskinesia (months to years)–> can be irreversible

Question 24

how do we minimize extrapyramidal effects

Answer 24

block cholinergic activity, restores normal balance
- ex) benztropine

Question 25

ADVERSE EFFECTS- Neuroleptic malignant syndrome
- what is it
- treatment

Answer 25

• fatal reaction to antipsychotics
• muscle rigidity, fever, altered mental status, unstable BP, myoglobinemia

treatment: discontinue drug, supportive therapy
- administer DANTROLENE or BROMOCRIPTINE

Question 26

ADVERSE EFFECTS- other

Answer 26

• drowsiness, confusion
• antimuscarinic activity
• alpha adrenergic–> lower BP, orthostat hypo
• depression of hypothalamus–> amenorrhea, galactorrhea, gynecomastia, infertility, erectile dys
• weight gain

Question 27

MAINTENANCE THERAPY
- for what kinds of PTs?
- how does it work

Answer 27

• PT w 2 or more psychotic episodes secondary to schizo receive maintenance therapy for AT LEAST 5 years
• use only 1 drug