Antipsychotic Agents Flashcards
Clinical Features of Schizophrenia
Positive symptoms
overactivity of dopamine neurons in the limbic system (mesolimbic pathway)
Clinical Features of Schizophrenia
Psychotic Symptoms
Delusions: false belief, often paranoid in nature
Hallucinations: false perception, usually voices
Clinical Features of Schizophrenia
Disorganized symptoms
Thought disorders–> wild trains of thought with irrational conclusions (inserted by an outside agency)
Clinical Features of Schizophrenia
Negative symptoms
hypoactivity of dopamine neurons in the prefrontal cortex (mesocortical pathway)
- Withdrawal from social contact
- Flattening of emotional responses
- Decreased motivation
- Poverty of speech
Clinical Features of Schizophrenia
Cognitive symptoms
Decreased attention span-executive function
Poor working memory
Abnormality of brain function in schizophrenics is due to overactivity in brain dopaminergic pathways, especially in the mesolimbic pathway
Dopamine Hypothesis of Schizophrenia
Virtually all antipsychotic drugs block __________ receptors
dopamine D2
Evidence exists for role of _______ (3) systems in SK
glutamate and serotonin and acetylcholine
↑ DA –>
Positive Symptoms
Delusions
Hallucinations
Disordered thoughts
↓ DA –>
Negative Symptoms
Blunted affect-anhedonia
Alogia - Asociality
Subserve the integration of sensory input and motor responses with affective or emotional data
Mesolimbic pathway
Involved in communication and social abilities
Mesocortical pathway
Part of basal ganglia (aka extrapyramidal tract) plays a central role in planned, coordinated movement
Nigrostriatal pathway
Hypothalamic neurons release DA in pituitary to inhibit prolactin release
Tuberoinfinduibular pathway
5HT2A receptors on DA neurons in the PFC decrease DA release. Block of these receptors by atypical agents results in _______ resulting in alleviation of negative symptoms of schizophrenia
Serotonin Hypothesis - 5HT2A Receptors
increased DA release
Activation of _______ was found to be basis of hallucinatory effects of drugs like LSD and mescaline
Serotonin Hypothesis - 5HT2A Receptors
5HT2A
________ on DA neurons in the PFC decrease DA release. Block of these receptors by atypical agents results in increased DA release resulting in alleviation of negative symptoms of schizophrenia
Serotonin Hypothesis - 5HT2A Receptors
5HT2A receptors
Glutamate Hypofunction Hypothesis
Cortical Glu –> GABA–> cortical Glu –> ↑ mesolimbic DA
Hypofunction in cortical NMDA-Glu neurons -remove GABA inhibition-activate DA Neurons -positive symptoms of schizophrenia
Positive symptoms of schizophrenia (delusions, hallucinations) are believed to result from:
Overactivity of cholinergic neurons in the cortex
Overactivity of dopamine neurons in the mesolimbic system
Cortical Glu –> GABA –> Glu –> GABA –> ↓ mesocortical DA
Glutamate Hypofunction Hypothesis
Hypofunction in cortical NMDA-Glu neurons remove inhibition of VTA GABA inhibit mesocortical DA negative symptoms of schizophrenia
TYPICAL VS ATYPICAL
Typical Agents [1st generation] – high D2 / 5HT2A blocking ratio
Atypical Agents [2nd generation] - low D2/5HT2A blocking ratio
Typical Agents [1st generation] – high D2 / 5HT2A blocking ratio
Good D2 block - good efficacy against positive symptoms
Good D2 block - high incidence of extrapyramidal toxicity
Atypical Agents [2nd generation] - low D2/5HT2A blocking ratio
Poor D2 block yet good antipsychotic efficacy (atypical)
Good 5HT2A block good efficacy against negative symptoms
Poor D2 block + good 5HT2A block reduced incidence of EPSE
Haloperidol
High potency ↑ D2 side effects (EPSE) but less ADRs via M-H1-α1 block
