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Chapter 11

PHAR 100 Chapter Notes - Chapter 11: Extrapyramidal Symptoms, Atypical Antipsychotic, Dopamine Receptor


Department
Pharmacology and Toxicology
Course Code
PHAR 100
Professor
Bill Racz
Chapter
11

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Lesson B.6 Classification of Mental Disorders Antipsychotic And Antidepressant Drugs
Objectives:
- Differentiate between psychoses, affective disorders and neuroses
- Describe the evidence that excessive dopaminergic activity underlies schizophrenia
- Describe the mechanism of action of antipsychotic agents
- Describe the adverse effects of phenothiazines and mechanisms responsible for these adverse
effects
- Differentiate between the adverse effects of phenothiazines, butyrophenones and clozapines
- Describe the mechanism of action of lithium as a therapeutic agent in manic-depressive illness
- List the adverse effects of lithium and one means of trying to minimize the adverse effects
- Classify the various types of depression
- Describe the amine hypothesis of depression
- Describe the types of depressants and their mechanisms of action
- Describe the adverse effects of different types of antidepressants
Psychoses
- Among the most severe psychiatric disorders
- Symptoms include: impairment of behaviour, incoherent thought processing, inability to
comprehend reality or to gain insight into their abnormalities, delusions and hallucinations
- Organic psychoses:
o Causes are understood and definable (toxic induced, metabolic or neuropathological
changes)
o Characterized by confusion, disorientation, memory disturbances and behavioural
disorganization
- Functional psychoses:
o Causes is unknown
o Characterized by retention of orientation and memory in the presence of severely
disordered thought or reasoning, emotion and behaviour
o Ie. Schizophrenia
Affective (Mood) Disorders
- Characterized primarily by a change in emotion or mood
- More often a single mood disorder mania or depression
- Mania elation, hyperactivity, uncontrollable thought and speech
- Depression intense feelings of sadness, self-disapproval, physical and mental slowing
- Manic-depressive disorder alternating high and low periods
Neuroses
- Individuals retain the ability to comprehend reality
- Characterized by mood changes (anxiety, panic, restlessness, feeling of unease), abnormalities of
thought/behaviour (obsessions, irrational fears, rituals or compulsions)
Schizophrenia:
- 1 in 100 people
- Characterized by positive and negative symptoms
o Positive symptoms delusions, hallucinations, bizarre behaviour, incoherence and
illogical actions
o Negative symptoms apathy, social withdrawal, lack of motivation
- Dopamine hypothesis cause of schizophrenia whereby circumstantial evidence suggest that
excessive dopaminergic activity
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- Neurotransmitters including serotonin, glutamate, gamma-aminobutyric acid and glutamic acid
may also be involved
- Atypical antipsychotics, clopzapine and quetiapine, are 5-HT antagonists while some glutamate
agonists also extinguish symptoms of schizophrenia
- Typical antipsychotic drugs block postsynaptic dopamine receptors
- Increases in dopaminergic activity can be caused by levodopa (precursor of dopamine) or
apomorphine (direct dopamine receptor agonist) induce or aggravate schizophrenia
- Dopamine receptor density has been shown (via positron emission tomography PET) to be higher
in schizophrenics than in non-schizophrenic individuals
Antipsychotic drugs
- Late 1950’s phenothiazines were introduced
- 1959 neurotransmitter, dopamine was recognized
- 1960’s it was found that the effects of dopamine and the secondary messenger cyclic AMP could
be blocked by the phenothiazine antipsychotic drug (antagonist at dopamine receptors)
- Antipsychotic action can be explained by antagonism of dopamine receptors in the mesolimbic and
mesofrontal systems of the brain (limbic system controls emotion and behaviour)
- Extrapyramidal movement disorders:
o Antagonism of dopamine receptors in the nigrostriatal system
o Parkinsonism-like symptoms, dystonia (involuntary muscle spasms), akathesia (anxiety,
restlessness, repetitive purposeless action
o Ie. Tardive dyskinesia a serious movement disorder characterized by involuntary
movements of the face, tongue, trunk and limbs
- Phenothiazine (endocrine effects):
o Dopamine in the hypothalamus exerts a tonic inhibitory effect on prolactin release from
the pituitary gland antagonizing dopamine receptors causes excess prolactin release
(hyperprolactinemia)
o Blockage of cholinergic (muscarinic) receptors therapeutic reduction of
extrapyramidal adverse effects but does cause blurred vision, dry mouth, constipation,
urination difficulties
o Blockage of serotonin receptors therapeutic reduction of extrapyramidal adverse
effects and negative symptoms of psychosis (apathy, social withdrawal, lack of
motivation); there are no known adverse effects
o Blockage of histamine receptors causes sedation, drowsiness and weight gain
o Blockage of α-adrenoceptors causes postural hypotension, dizziness, reflex
tachycardia
o Primarily relieve positive symptoms of schizophrenia
- Haloperidol
o Chemical structures is very different from phenothiazines (ie. chlorpromazine)
o Competitively blocks dopamine receptors
o Very similar pharmacological effects between haloperidol and phenothiazines:
High propensity for producing extrapyramidal movement disorders
Decreased sedation and hypotension
o Useful alternative to those who do not react to phenothiazines
o Primarily relieve positive symptoms of schizophrenia
- Second Generation Antipsychotics (atypical antipsychotics
o Introduced in 1990
o Relieve positive and negative symptoms of schizophrenia
o Lower propensity to produce extrapyramidal side effects
o Block both dopamine and serotonin receptors
o Include: clozapine, risperidone, olanzapine
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