💗 Schizophrenia Therapy- Antipsychotic Drugs Flashcards
(14 cards)
Discovery of Antipsychotics
Q: Who first published a paper on the use of chlorpromazine for schizophrenia, and when?
Jean Delay and Pierre Deniker in 1952. Chlorpromazine was used extensively to treat psychiatric conditions, including schizophrenia.
Agonists vs. Antagonists
Q: How do agonists and antagonists differ in their effects on synaptic activity?
- Agonists increase synaptic activity by boosting neurotransmitter release or mimicking neurotransmitters.
- Antagonists block receptor sites, reducing neurotransmitter effects.
Conventional (Typical) Antipsychotics
Q: What are conventional antipsychotics, and how do they work?
- Developed in the 1950s (e.g., chlorpromazine).
- Primarily block D2 dopamine receptors, reducing dopamine activity.
- Also affect D1, D3, D4, D5, and serotonin receptors (5-HT, SHT-2).
Mechanism of Chlorpromazine
Q: How does chlorpromazine reduce dopamine activity?
- Blocks postsynaptic D2 receptors → lowers neural activity.
- Initially, presynaptic neuron releases more dopamine (compensation).
- Dopamine production eventually drops → synapse has less dopamine.
- Results in reduced positive symptoms (hallucinations, delusions) via the ** mesolimbic pathway.**
Atypical Antipsychotics
Q: How do atypical antipsychotics differ from conventional ones?
- Developed since the 1990s (e.g., clozapine).
- Weaker D2 blockade but affect D1, D4, and serotonin (5-HT2A) receptors.
- Fast-off theory (Seeman, 2002): Bind loosely to D2 → fewer side effects.
- Shorter half-life: D2 occupancy drops within 24 hours (vs. >24h for typical antipsychotics).
Fast-Off Theory (Seeman, 2002)
Q: What does the fast-off theory propose about atypical antipsychotics?
They bind loosely to D2 receptors, providing therapeutic effects without prolonged blockade, reducing side effects (e.g., extrapyramidal symptoms).
Role of Serotonin in Atypical Antipsychotics
Q: How do atypical antipsychotics interact with serotonin?
They antagonize 5-HT2A receptors as strongly as D2 receptors, which may help improve negative symptoms and cognitive function.
Evaluation: Effectiveness of Conventional Antipsychotics (Cole, 1964)
Q: What did Jonathan Cole (1964) find about conventional antipsychotics?
- 75% of patients improved with antipsychotics vs. 25% with placebo.
- 0% worsened on antipsychotics vs. 48% on placebo.
- Revolutionised psychiatry by showing schizophrenia could be treated with drugs.
Evaluation: Atypical vs. Conventional Antipsychotics (Ravanic, 2009)
Q: How do atypical antipsychotics compare to conventional ones in effectiveness using ravanics study?
Study Details: Compared clozapine (atypical), chlorpromazine, and haloperidol in 325 schizophrenia patients over 5 years
• Effectiveness:
Clozapine showed significantly better improvement in psychometric scores measuring schizophrenic symptoms
Clozapine had fewer adverse effects than both conventional drugs
• Conclusion: Atypical antipsychotics (like clozapine) are more effective and preferable for treating schizophrenia
Evaluation: Problem of Non-Compliance
Q: Why is non-compliance an issue in assessing antipsychotic effectiveness?
Many schizophrenia patients lack insight and stop taking medication.
Rettenbacher et al. (2004):
- 54.2% fully compliant
- 8.3% partially compliant
- 37.5% non-compliant
Real-world effectiveness may be lower than in controlled studies.
Evaluation: Ethical Issue – Side Effects
Q: What are the ethical concerns regarding antipsychotic side effects?
Physical: Tremors (Parkinsonism), seizures, irregular movements.
Cognitive/Emotional: Blunting, feeling “numb.”
Ethical dilemma: Do benefits outweigh harms for each patient?
Evaluation: Ethical Issue – Chemical Restraints (Szasz, 1960)
Q: What is the antipsychiatry argument against antipsychotics?
Thomas Szasz (1960): Antipsychotics act as “chemical restraints”—controlling behavior rather than curing illness.
Raises ethical questions: Are drugs used for patient well-being or social control?
Evaluation: Social Impact – Deinstitutionalization (Lawrie, 2011)
Q: How did antipsychotics change schizophrenia treatment socially?
Stephen Lawrie (2011): Shifted care from asylums to community-based treatment.
Benefits:
Patients could live independently.
Reduced costs of long-term hospitalization.
Evaluation: Social Risk – Violence & Non-Compliance
Q: What are the risks if schizophrenia patients stop medication?
Tihonen et al. (2006): 37x higher suicide risk in non-compliant patients.
NCISH (2015): 346 homicides in England (2003-2013) by people with schizophrenia history.
Not direct causation, but non-compliance is a risk factor for violence.
