Schizophrenia Drugs Flashcards
Whats the relative prevalence of schizophrenia? Is it heritable?
Affects 1% of the population. 48% heritability between identical twins.
Give 3 positive symptoms, 3 negative symptoms and 3 cognitive deficits of schizophrenia.
Positive symptoms: hallucniations, delusions and disorganized thoughts. Negative symptoms: anhedonia, avolition (reduced ability to start and sustain activities), alogia and affective flattening. Cognitive deficits- memory, attention, planning.
Describe the outcomes of schizophrenia.
4 outcomes:1) 10-20% completely resolves 2) 30-35% recurring but with full recovery each time 3) 30-35% recurring but incomplete recovery each time, leading to a persistent defective state which becomes pronounced each successive relapse 4) 10-20% downhill course from the beginning.
Describe the dopamine hypothesis for schizophrenia. Give 2 supporting evidence.
Excessive dopamine in mesolimbic and nigrostriatal regions give positive symptoms D2. Dopamine deficit in frontal regions D1 RECEPTORS give negative symptoms.
Dopamine agonists can induce psychotic symptoms.
Strong correlation between antipsychotic potency of drugs and their activity at blocking D2 receptors.
Describe the glutamate theory for schizophrenia and give 3 supporting evidence.
Glutamate deficit.
Evidence: NMDA receptor antagonists produce psychotic symptoms.
Reduced glutamate concentrations and glutamate receptor densities in post mortem schizophrenic brains.
Dopamine is inhibitory and glutatamate is excitatory on GABA-ergic neurons that project to thalamus and gate sensory input. So too much dopamine or too little glutamate will cause more supression GABAergic neurons, which disables its gate function and allow uninhibited sensory input to reach the cortex.
Is schizophrenia genetic?
9 susceptibility genes have been identified associated with glutamate and dopamine transmission. Neuregulin-1 polymorphisms affects synaptic development and plasticity.
Describe the MOA of neureleptics
Antagonists to D2 receptors which treats the positive symptoms.
Delayed effect because first response of the neurone is an increase in activity and DA synthesis.
Often affect other receptors too.
Whats the difference between first and second generation neuroleptics?
First generation neuroleptics have greater affinity for D2 receptor blockade, whilst second generation have greater affinity for 5HT receptor blockade.
First generation- Chlorpromazine- ant muscarinic side effects. Haloperidol- Parkinson like side effect.
Second generation- Olanzapine causes weight gain. Clozapine causes agranolcytosis.
Name 4 other side effects of neurelptics?
ANTI-EMETIC. effects. ACUTE DYSTONIA (same as Parkisonian -like side effects), TARDIVE DYSKINESIA (involuntary movements, after months/years, made worse by drug withdrawl or anticholinergics- proliferation of presynaptic D2 receptors of glutamate excitotoxic striatal neurodegeneration), ENDOCRINE EFFECTS, BLCOKING A ADRENOCEPTORS (orthostatic hypotension).
