Antipsychotics Flashcards
Schizophrenia
psychiatric disorder affecting approx. 1% of the population
manifests as hallucinations, delusions, disordered thinking/communication
3 Categories of Symptoms
1. Positive 2. Negative 3. Cognitive Deficits
Positive Symptoms of Schizophrenia
overt symptoms that should not be there
- make themselves known by presence
hallucinations
delusions
disorganized thoughtsNegative Symptoms of Schizophrenia
lack of a characteristic that should be there
reduced speech (alogia)
lack of emotional/racial expression (affective flattening)
diminished ability to begin & sustain activities (avolition)
decreased ability to find pleasure (anhedonia)
social withdrawal (asociality)
Cognitive Deficits with Schizophrenia
difficulties with aspects of cognition
memory
attention
executive function
- planning
- decision-making
- goal-setting
DSM-5 Key Features of Schizophrenia
1. Delusions 2 Hallucinations 3. Disorganized Thoughts/Speech 4. Disorganized Motor Behaviour 5. Negative Symptoms
Causes of Schizophrenia
unknown for sure; associated with mesocorticolimbic system
hyperactivity in mesolimbic DA pathway
hypoactivity in mesocortical DA pathway
behavioural outcome of an aberration in neurodevelopmental processes that begin long before the onset of clinical symptoms & is caused by combination of environmental and genetic factors
onset is usually in late teens/early 20s in males; later in females
Discovery of Antipsychotic Medications
Accidental by French military surgeon Henri Laborit
Antihistamines to reduce surgical shock/sedate patient
1952 found to be effective in agitated/mentally disturbed patients
1953 marketed
in 30 years following the introduction the number of patients in US mental institutions dropped by 80%
Dopamine Hypothesis of Schizophrenia
positive symptoms of schizophrenia arise from excessive DA release
- antipsychotic drugs act as antagonists for D2
Receptors (in Nucleus Accumbens)
- amphetamine causes psychotic symptoms via
increased dopamine release
doesn’t explain the cognitive/negative symptom profiles
DA antagonists not very effective in treating symptoms
DA/Glutamate Hypothesis of Schizophrenia
diminished levels of glutamate release throughout cerebral cortex and limbic system
- ketamine and phencyclidine cause users to exhibit
behaviours consistent with positive, negative, and
cognitive deficits
can account for reduced DA in prefrontal cortex and excess DA in limbic system
Typical Antipsychotic Drugs
classical/neuroleptic antipsychotics
either phenothiazines (e.g. Thorazine) or butyrophenones (e.g. Haldol)
primarily D2 receptor blockers
effective for treating positive symptoms
1/3 of individuals experience no improvement
adverse extrapyramidal symptoms are typical
- tremor, muscle rigidity, involuntary movement
D2 receptor blocking in the nucleus accumbens treats symptoms
D2 receptor antagonism in basal ganglia causes EPS
Atypical Antipsychotic Drugs
novel antipsychotic drugs
weak affintiy for D2 receptors
- bind loosely
- have dissociation constants higher than DA or typicals
high affinity for D3 & D4 receptors
antagonize 5-HT2A (5-HT2a-mGlu receptor complex)
Abilify (3rd Generation Antipsychotics)
partial agonist at the D2 receptor
Routes of Administration for Antipsychotic Drugs
all typicals and atypicals are available in pill form but low patient compliance requires other RoAs
depot injections = drug dissolved in oil and injected into muscle
Absorption of Antipsychotics
most are readily absorbed from the digestive system
peak plasma concentration varies (up to days)
Distribution of Antipsychotics
easily cross BBB
highly lipophilic
- considerable plasma binding - tends to absorb into body fats & release slowly
