Organic physchosis : secondary to preexisting medical condition like : physical trauma, temporal lobe epilepsy, dementia, neurologic and endocrine disease, metabolic abnormalities)
Pathophysiology of Psychosis:
Dopamine hypothesis of schizophrenia:
1- Excessive limibic dopaminergic activity plays role in physchiosis
2- Diminished cortical and hippocampal dopaminergic activity
Classification of Antipsychotics
1- First generation “typical “antipsychotics : chlorpromazine , Fluphenazine , Haloperidol , Mesoridazine , Perphenazine , Thioridazine , Trifluoperazine .
-Act as predominately by blocking the dopamine D2 receptor in the brain
2- Second generation “ atypical” antipsychotics : Clozapine , Olanzapine , Quetiapine , Asenapine , Sulpiride , Amisulpiride , Aripiprazole, Melperone, Risperidone .
Aripiprazole : Act as D2 partial agonist , it lowers prolactin level , it also cause nausea , and it has least effect on QT interval and it doesn’t likely cause hyperglycemia .
Clozapine : has high affinity for D4 receptor , it also blocks D1,D2 , α adrenoceptor and muscrianic .
Olanzapine : it cause D1,D2, D4 ,SHT antagonism . It also cause weight gain and hyperglycemia .
Pharmacological actions :
1-Antiphyschotic actions :
Decrease the positive symptoms of schizophrena by causing D2 receptor blockade mesolimbic
Atypical antiphyschotic such as clozapine improve negative symptoms
2-Blockade of dompaine receptor in Nigrostriatal pathway :
Leads to extrapyramidal symptoms which is characterized by Akathisia , parkinsonism , Dystonia ( sustained contraction of muscles leading to twisting and distorted posture )
“Nigrostriatal pathway is a dopaminergic pathway that connects the substantia nigra pars compacta(SNc) with the dorsal striatum “.
3- Blockade of dompamine receptors in tuberoinfundibular pathway :
It will cause hyperprolactinemia which leads to galactorrhoea .
4- Blockade of α-1 adrenergic receptor :
It will cause orthostatic hypotension .
Mechanism of action :
Most of first generation drugs block dopamine receptors in brain and it’s periphery .
Note :Dopamine receptors have five forms : D1, D2, D3, D4, D5.
D1, D5 receptors activate adenylyl cyclase, often exciting neuron
D2, D3, D4 receptors inhibit adenylyl cyclase and mediate k+ channel opening leading to
Neuronal hyperpolarization
Advantages of atypical over typical anti pyschotics :
1- Absence or marked reduction in EPS
2- Less incidence of hyperprolactinemia
3- Sexual dysfunction and skin problems are less
4- Better tolerance and compliance to the drug
Main adverse effects “ disadvantages “of Second generation “ atypical” antipsychotics :
• Agranulocytosis : (marked decrease in the number of granulocytes. )
• Myocarditis and cardiomyopathy : Myocarditis : is inflammation of the heart muscle .Cardiomyopathy is : group of diseases that affect heart muscle .
• Have high possibility of weight gain and hyperglycemia
Clozapine and Risperidone lead to substantial blockade of α-1 adrenergic receptor that may account for their helpful effect on negative symptoms of schizophrenia .
References :
1. Burgy, M. (20 August 2008). “The Concept of Psychosis: Historical and Phenomenological Aspects” (PDF). Schizophrenia Bulletin. 34 (6): 1200–1210
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