Pharmacological Management Of Psychosis Flashcards
What are the action of typical/first generation antipsychotics?
Based on the dopamine theory of schizophrenia, therefore it antagonises D2 receptors on dopaminergic neurons to inhibit dopamine transmission in all 4 dopamine pathways:
-> Nigrostriatal
-> Mesolimbic
-> Mesocortical
They also have antagonising effects on histaminergic H1 receptors, muscarinic receptor and alpha-1 receptors.
What are the action of atypical antipsychotics?
Also known as second generation antipsychotics, they act as antagonists to both D2 dopamine receptors and serotonin receptors, typically 5HT2A and have a lower risk of extrapyramidal side effects. This may be due to their weaker binding to D2 receptors compared to first generation antipsychotics.
What are the side effects with typical antipsychotics?
Lowered seizures threshold, causing a greater risk.
Anti muscarinic effects cause dry mouth, urinary retention and constipation.
Inhibition of the tuberoinfundibular pathway leads to excessive prolactin release and causing sexual dysfunction. Females experience galactorrhoea, breast soreness and amenorrhea. Males experience impotence and libido.
A1 blocking effects causes orthostatic hypotension and dizziness.
Antagonism of the nigrostriatal pathway for movement leads to extrapyramidal side effects.
Inhibition of histamine causes sedation
What are the extrapyramidal side effects?
Akithisia=restlesness
Dystonia= continuous muscle spasms
Parkinsonism- rigidity
Bradykinesia= slowing of movement
Tardive dyskinesia= irregular jerky movements affecting the lower face
This occurs due to long term use of antipsychotics which cause hypersensitivity of dopamine receptors in the nigrostriatal pathway.
What are the side effects of second generation antipsychotics??
Lower risk of extrapyramidal side effects due to disassociation of second gen antipsychotics from D2 receptors which allows a degree of dopamine neurotransmission.
Weight gain and metabolic syndrome with dyslipidaemia and hyperglycaemia.
Histamine antagonism with sedation.
Agranulocytosis and neutropenia
What are the contraindications for first generation antipsychotics?
Use of CNS depressants such as barbiturates and opioids
Anticholinergic medications
Seizure disorder
History of tardive dyskinesia
Pregnancy in the first trimester and breastfeeding
What is the action of haloperidol?
First-generation antipsychotic indicated for psychosis in schizophrenia, acute delirium and bipolar. It can also be given for nausea and vomiting pre-operation. Haloperidol has significantly high extrapyramidal side effects and prolactin elevation of gynaecomastia and galactorrhoea, with milder weight gain and hypercholesterolemia.
What is the action of fluphenazine?
First generation typical antipsychotic which blocks D1 and D2 receptors to treat schizophrenia. It has strong extrapyramidal side effects and prolactin release to cause sexual dysfunction, but with little metabolic side effects.
What is the action of trifluoperazine?
First generation antipsychotic indicated for schizophrenia or management of psychomotor agitation which blocks D1 and D2 receptors in the brain with a high risk of extrapyramidal side effects and prolactin elevation to cause galactorrhoea and prolactin elevation.
It MUST be avoided with CNS depression and phaemochromocytoma.
What is the action of chlorpromazine?
First generation antipsychotic which blocks D1 and D2 receptors indicated for schizophrenia and mania. It has a significantly high risk for hypercholesterolemia, weight gain, anticholinergic effects and orthostatic hypotension however a very low risk of extrapyramidal side effects.
It should be avoided in CNS depression and hypothyroidism.
What is the action of clozapine?
Atypical antipsychotic which antagonises both D1 and D2 receptors, 5HT2-A serotonin receptors and lesser a1, histamine and acetylcholine antagonism. It is indicated for schizophrenia and psychosis in Parkinson’s disease.
It has a significantly high risk of metabolic syndrome, reduced seizure threshold and agranulocytosis.
What is olanzapine?
Atypical antipsychotic which antagonises D1, D2, histamine, 5HT2-A, adrenergic receptors and muscarinic. The antagonism of olanzapine at the D2 receptor is easily disassociatable which allows for a degree of dopamine transmission with the use of olanzapine.
There is a significantly high risk for metabolic syndrome, however a low risk for anticholinergic and alpha adrenergic receptor side effects compared to clozapine.
What is the action of risperidone?
Second generation antipsychotic which antagonises D2 and 5-HT2A receptors in the brain. It is one of the few atypical antipsychotics with a high risk of extrapyramidal side effects and prolactin elevation.
What is the action of quetiapine?
Antagonises D2 and 5-HT2A receptors with partial binding to the NA transporter as well as the histamine, acetylcholine and a1 receptor.
Quetiapine can be used to treat both schizophrenia and major depressive disorder and has a significantly high risk of metabolic syndrome of weight gain and hypercholesterolemia.
What is the risk with the use of antipsychotics?
Neuroleptic malignant syndrome, a disorder that occurs when there is excessive inhibiton of dopamine that leads to FARM:
->Fever
->Autonomic dysregulation of hypertension, tachycardia and diaphoresis
->Rigidity
->Mental state changes
The inhibiton of dopamine may increase levels of calcium in peripheral muscles which increases its contractility.
