1st Generation Antipsychotics

Question 1

First generation antipsychotics, general

Answer 1

D2 receptor antagonists

Dominated treatment from 1952 to 1990

Thorazine (chlorpromazine)
○ first AP drug, developed for allergies, then used as a sedative prior to surgery
• Healthcare providers noticed sx reduction in SZ patients prior to surgery

Question 2

Mesolimbic DA pathway

Answer 2

Affiliated with reward-related cognitions

Large number of D2 receptors

Increased activation = positive symptoms of psychosis

It’s believed atypicals reduce mesolimbic dopamine
*tx effects generally require 1-3 weeks

Question 3

Mesocortical DA Pathway

Answer 3

Affiliated with cognitive control
*high number of D1 and D4 receptors

Decreased activation = negative symptoms and cognitive deficits

*Antipsychotics do not reduce negative symptoms
[Typicals may actually increase negative symptoms]

Dopamine agonists such as stimulants like cocaine, actually reduce negative symptoms

Question 4

Nigrostriatal DA Pathway

Answer 4

Involved with smooth motor movements

Destruction leads to Parkinsonism

Typicals decrease dopamine in the nigrostriatal, causing extrapyramidal symptoms (EPS)

Decreased fluidity and flow of motor movements

Question 5

Tuberoinfundibular DA Pathway

Answer 5

Linked with the pituitary gland

Regulates sex drive

Blocking DA here yields changes in sex drive and alterations to secondary sex characteristics

*e.g. gynomastia

Question 6

Extrapyramidal Symptoms (EPS)

Answer 6

Akathisia

Parkinsonism

Tardive dyskinesia

Dystonia

Question 7

EPS: Akathisia

Answer 7

Motor restlessness or the inability to sit still

Considered by patients to be the least tolerable side effect

Responsible for suicidal behavior

Question 8

EPS: Parkinsonism

Answer 8

Tremor

Bradykinesia (slow awkward movements)

Rigidity

Postural instability

Question 9

EPS: Tardive dyskinesia

Answer 9

Characterized by repetitive, involuntary movements:

Grimacing; Tongue movements; Lip pursing, smacking, puckering; Excessive eye blinking

Rapid, involuntary movements of the limbs, torso, and fingers may also occur.

TD is often misdiagnosed as a mental illness

Question 10

EPS Treatment

Answer 10

Adjunctive anticholinergic drug treatment
e.g
Cogentin, Artane, Benadryl
*Monitor anticholinergic SFX particularly if taken with other meds with anticholinergic activity (e.g. TCAs)

Decrease dosage of antipsychotic
*or try different AP (atypical, fewer EPS)

DA facilitators
e.g. L-Dopa

Beta-blockers
*e.g. propranolol – for akathisia

Question 11

AP Potency

Answer 11

Based on “dopamine affinity”

How much is needed for a therapeutic effect
*i.e. dosage needed to block d2 receptors

High potency = higher EPS, lower anticholinergic sfx
e.g. Haldol 10mg

Low Potency= lower EPS, higher anticholinergix sfx
e.g. Thorazine 1000mg

Question 12

Low Potency AP’s

Answer 12

e. g. Thorazine
e. g. Melorill

• Anticholinergic effects including sedation and confusion, but less EPS
• Start at low level–confusion, dizziness, hypotensive effect

Question 13

HIgh Potency AP’s

Answer 13

e. g. Prolixin
e. g. Haldol

*More EPS, but less anticholinergic effects

Question 14

Antipsychotics: indications

Answer 14

SZ

schizoaffective disorder

bipolar

• mood stabilization
• and/or when psychotic features are present

psychotic depression

delirium

dementia

trichotillomania

augmenting agent in treatment resistant anxiety disorders

Question 15

EPS: Dystonia

Answer 15

Sustained or repetitive muscle contractions

Twisting and repetitive movements

Abnormal fixed postures

Question 16

Parkinsonism vs Tardive Dyskinesia

Answer 16

Parkinson’s = Difficulty moving

TD = Difficulty NOT moving