Antipsychotics

Goals
Pharmacy students
should:
be familiar with the
symptoms & health
consequences of
schizophrenia
be able to describe the
mechanism(s) of action
and adverse effects of first-
generation antipsychotics
 Schizophrenia

The Greek translation is schizein split and phren

mind which refers to a split from reality. A group
of severe disorders characterized by atypical:
1. Cognition
2. Behavior
3. Emotions NOT Multiple Personality
Disorder
 Symptoms of Schizophrenia
Positive symptoms: the presence of inappropriate
behaviors
delusions: thoughts
hallucinations: auditory >>> visual > other
disorganized talking: word salad
movements

Negative symptoms: the absence of appropriate

behaviors
flat affect: joy, anger, disgust
anhedonia
catatonia: waxy flexibility
 Example Patient
Delusions of grandeur
inappropriate beliefs about
ones self-worth or special
powers

Gerald (upto 2:30): http://www.youtube.com/watch?v=gGnl8dqEoPQ

 Epidemiology of
Schizophrenia

Frequency: 0.7%
Sex: Males > Females (1.4:1) in # and severity
Low SES (downward drift)
Rule of thirds
Comorbidity with depression & smoking

Sources: Anna K. Kring

 History of Antipsychotics
1953: an antihistamine agent (cholpromazine) is found to
improve psychosis in schizophrenics
1960-1970: identification of D2 blockade as the key mechanism,
development of these first-generation of antipsychotic agents
 Dopamine System I
nigrostriatal: substania nigra (soma) to striatum (axons)

Stahl, S. (2008). Essential Psychopharmacology, p. 330.

 Antipsychotics & Tardive Dyskinesia

Chronic blockade of D2 receptors leads This may cause involuntary movements.

them to up-regulate.

tardive: slow or belated onset

dyskinesia: presence of involuntary movements, tongue thrusts, lip smacking, eye blinking

Potentially permanent!

Example: 4:20 to 5:50: http://www.youtube.com/watch?v=QYYx1mZDpPw

 TD = Extrapyramidal Symptoms (Long-Term)

Brodal (2010). The central nervous system. p. 83.

 Extrapyramidal Symptoms (Short-term)
Pseudo-Parkinsonism:
tremor
rigidity
bradykinesia
dystonia: involuntary muscle spasms
torticollis: abnormal head or neck position
akathisia: severe sensation of restlessness,
strong desire to move

Excellent Examples (0:30- 4:50-9:15): http://www.youtube.com/watch?v=WAg2iLEWVh0

 Dopamine Inhibits Acetylcholine

Stahl, S. (2008). Essential Psychopharmacology, p. 338.

 D2 Inhibition & Increased ACh

Stahl, S. (2008). Essential Psychopharmacology, p. 339.

 Solution: Anti-cholinergics

Stahl, S. (2008). Essential Psychopharmacology, p. 339.

 Dopamine Inhibits Prolactin

Consequences
amenorrhea
galactorhea
sex interest
gynecomastia

Stahl, S. (2008). Essential Psychopharmacology, p. 334.

Dopamine & Mood

Dopamine projections to nucleus accumbens

Increasing dopamine increases reward
anti-psychotics block this pathway
 Non-Selectivity of FGA

Stahl, S. (2008). Essential Psychopharmacology, p. 338, 340.

Haloperidol

MOA: D2 antagonist, 1 antagonist

Indications: acute psychosis/schizophrenia
Adverse Effects: extrapyramidal symptoms
(EPS), hypotension
 Summary: Pros & Cons
FGAs have strong efficacy against + symptoms.
FGAs either do not help symptoms or exacerbate them.
The primary concern with FGAs is long-term development of
tardive dyskinesia although acute EPS impair the quality of
life of schizophrenics.

Stahl, S. (2008). Essential Psychopharmacology, p. 369.

 Terminology
Neuroleptic = major tranquilizer =
antipsychotic
First Generation Antipsychotic = Typical =
Conventional
 Reduced Lifespan
(N = 5,036,662)

Male Male Female Female

Life Expectancy Years Life Years Lost
Lost Expectancy
All (Psychiatric 76.5 NA 80.9 NA
History - )
Schizophrenia 57.8 18.7 64.6 16.3
Bipolar 62.9 13.6 68.8 12.1

Contributing Factors
suicide, accident, homicides,
self-care (diet/smoking), metabolic (?)

Laursen (2011). Schizophrenia Research, 131, 101-104.