2. 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
3. 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
4. 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
5. Example Patient
Delusions of grandeur
inappropriate beliefs about
one’s self-worth or special
powers
Gerald (upto 2:30): http://www.youtube.com/watch?v=gGnl8dqEoPQ
6. 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
7. 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
8. Dopamine System I
• nigrostriatal: substania nigra (soma) to striatum (axons)
Stahl, S. (2008). Essential Psychopharmacology, p. 330.
9. 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
10. TD = Extrapyramidal Symptoms (Long-Term)
Brodal (2010). The central nervous system. p. 83.
11. 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
19. 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.
20. Terminology
• Neuroleptic = major tranquilizer =
antipsychotic
• First Generation Antipsychotic = Typical =
Conventional
21. 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.
Editor's Notes
Psychosis is the older terminology to refer to distorted or non-existent sense of reality.
Tardive= slow or belated onset.
A pair of protrusions (tracts) are most pronounced at upper medulla. The pyramids are less obvious in the lower medulla. EPS also includes akinesia (inability to initiate movement) & pseudo-Parkinson’s.
“Neuroleptic drug-induced parkinsonism is phenomenologically identical to idiopathic parkinsonism. Both are characterized by the triad of tremor, rigidity, and bradykinesia. The tremor is rhythmical with a to and fro motion which is usually greater at rest. Rigidity is most easily examined in the limbs and perceived as a rachet-like resistance during passive motion. Bradykinesia is a reduction in spontaneous activity, such as mask-like facial expression, decreased associated arm movements while walking, and decreased ability to initiate movement”.
Dopamine acts normally on D2 receptors in the striatum as in inhibitor to decrease the release of acetylcholine.
Diphenhydramine is also a potent competitive antagonist of muscarinic cholinergic receptors.
The tuberoinfundibular pathway refers to a population of dopamine neurons in the arcuate nucleus of the mediobasal hypothalamus (the 'tuberal region') that project to the median eminence (the 'infundibular region'). Dopamine released at this site regulates the secretion of prolactin from the anterior pituitary gland.
Vental Tegmental Area has dopaminergic somas.
Alpha1 blockade results in orthostatic hypotension. Anti-histamine can increase appetite resulting in weight gain.
Haloperidol causes difficulty swallowing (dysphagia) which can increase likelihood of choking and aspiration pneumonia.