Antipsychotic drugs - Pharmacology + pathophysiology
9 important questions on Antipsychotic drugs - Pharmacology + pathophysiology
The use of what is a strong association with the development of schizophrenia?
Which four pathways are there and which two are involved in the pathology of schizophrenia?
The other two are also involved but more into side effects.
Dopamine pathways how are they related to schizophrenia?
The mesolimbic and the mesocortical pathway are important for dopamine.
- Overactivity in the mesolimbic pathway D2 receptors causes delusions and hallucinations =positive symptoms
- Decrease in activity in the mesocortical D1 receptors pathway causes negative symptoms and positive symptoms and maybe cognitive side effects.
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What is evidence for the hypothesis that dopamine is related to schizophrenia?
- The effect of drugs: Drugs that enhance dopaminergic function such as amphetamines will produce or enhance positive psychotic symptoms.
- All known antipsychotics are dopamine D2 receptor antagonists
- Correlation between clinical potency and affinity for D2 receptors among antipsychotic drugs
- Imaging studies: Displacement of the D2 antagonist raclopride in the striatum occurred following administration of amphetamine to patients...
- Patients with schizophrenia have a greater dopamine release after taking amphetamines.
Dopamine receptors; tell something about them and their relation to drugs (5)
- Two groups
2: D2,3,4
- Some drugs have high affinity with the D1 and some with the D2 family.
- Different effects on the cells that express them (inhibiting or activation adenylate cyclase)
- Only for drugs that bind to the D2 receptors: the higher the affinity the higher the therapeutic potency (correlation).
- All the drugs work equally as good against psychosis but lower potency means more side effects.
Drugs with a low potency, what do they do beside blocking the dopamine receptors?
- Sedation (Anti-histaminic)
- Anticholinergic, dry mouth, blurred vision, constipation (Anti-muscarinic)
- Orthostatic hypotension (alpha-adrenergic antagonism)
You get these side effects because you need to give them on a higher dose. Depending on personal situations you choose the best medication.
But what is the downside of the high potency drugs?
D2 receptors => problems with movement => substantia nigra.
Dystonia: cramp
Dyskinesia: in moving a problem
+ the symptoms mentioned on the picture.
What is so special about clozapine?
- No extrapyramidal symptoms.
- They bind with high affinity to 5-HT2A, D2, 5-HT1A, 5-HT2C, 5-HT1D, (D1) and α-adrenergic receptors.
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Why is clozapine not so perfect?
Olanzepine - structurally similar to clozapine, similar therapeutic efficacy and side effect profile (no agranulocytosis).
Quetiapine - similar to olanzapine but has fewer anti-cholinergic and anti-adrenergic side effects.
Risperidone - similar to olanzepine but has no anti-cholinergic effects.
Sertindole - has no anti-muscarinic or anti-cholinergic effects but it prolongs the Q-T interval which can lead to cardiac arrhythmias.
Ziprasidone – less weight gain
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