Antipsychotics Flashcards
What is psychosis
Variety of mental disorders with delusions , auditory or visual hallucinations and disorganized thinking
What is schizophrenia
Particular kind of psychosis with clear sensorium and marked thinking disturbance
What are the positive symptoms of schizophrenia
Delusions hallucinations thoughts disorder abnormal disorganized behavior catatonia
Negative symptoms of psychosis
Social withdrawal flattening of emotional responses anhedonia reluctance to perform every day tasks chronic and persistent and less responsive to some antipsychotic agent
Do we know the cause of psychosis
Still unclear but might be linked to genetics and environment
What is the serotonin hypothesis
Hallucination are produced by LSD and mescaline which are serotonin agonist
What is a key factor in mechanism of action of antipsychotic
Blockades of serotonin receptor 5-HT2a
What drugs are 5-HT2c inverse agonist
Clozapine
asenapine
Olanzapine
What happens wonder stimulation of 5HT2c
Inhibition of cortico and Limbic dopamin release
What is the dopamine hypothesis
Psychosis might be due to excessive Limbic dopaminergic activity
What happens if the drug increases dopaminergic activity
Aggravate schizophrenia psychosis or psychosis de novo produced
What type of reçeptors density is increaesed in the brain of post mortem schizophrenic
Dopamine receptor
What is the glutamate hypothesis
NMDA receptor do not function well so there’s reduced inhibitory influence on the neuronal function which contributes to schizophrenia
What are the classes of drugs part of the first generation antipsychotics
Phenothiazines
Thioxanthenes
Butyrophenone
example of phenothiazines
Chlorpromazine Thioridazine Trifluoperazine Perphenazine Fluphenazine
Example of thioxanthenes
Thiothixene
Examples of butyrophenone
Haloperidol
droperidol
Class of drugs in second-generation antipsychotics
Atypical
miscellaneous
Examples of atypical antipsychotics
Clozapine Asenapine Olanzapine Quetiapine Sulpiride Amisupride Paliperidone Risperidone Sertindole Ziprasidone Zotepine Aripiprazole
Example of miscellaneous antipsychotics
Pimozide
Molindone
Types of phenothiazines with sedation& weight gain effects
Aliphatic derivatives and piperidine derivatives
Most potent phenothiazines types
Piperazine derivatives
Most widely used butyrophenone
Haloperidol
ExAmple of diphenylbutylpiperidines
Pimozide
Clopimozide
Fluspirilene
Penfluridol
The more potent with less autonomic effect l , phenothiazines or butyrophenone
butyrophenone
Prototype of atypical antipsychotic
Clozapine
Active metabolite of risperidone
Paliperidone9 hydroxyrisperidone
Main moa of atypical antipsychotic drugs
Alter 5HT2a receptor activity With synergy at Partial agonist of 5-HT1a
Name of of atypical antipsychotic that are potent for D2 and D3 receptors and antogonize 5HT7
Amisulpride
Sulpiride
Systemic availability of haloperidol
65%
Systemic availability of chlorpromazine and thioridazine
25-35%
Are antipsychotic drugs highly lipid soluble and protein bound
Yes
Dube antipsychotic drugs have large volumes of distribution
Yes
What is the average time for a relapse of stable patient with schizophrenia who discontinue the medication
Six months
How is relapse after discontinuation of clozapine
It’s very rapid and severe so should never be discontinued abruptly unless needed
 Metabolism of antipsychotic drugs
Oxidation or the methylation by liver cytochrome P450- cyp2d6, CYP1A2, cyp3a4
Would you expect antipsychotic drugs to interfere with metabolism of other drugs at typical clinical dose
No
What mechanism is that the basis of efficacy of phenothiazine antipsychotic drugs
D2 receptor blockade
Why are they adverse effects with phenothiazines antipsychotics
Block Alfa Adrenergic receptors, muscarinic receptors , h1 receptors , serotonin receptors
Most closely related pathway to behavior and psychosis
Mesolimbic Mesocortical pathway
Pathway involved in coordination of voluntary movement
Nigrostriatal pathway
This system neurons release dopamine which inhibits prolactin secretion from anterior pituitary
Tuberoinfundibular system
System involved in eating behavior
Medullary periventricular pathway
Pathway that regulates anticipatory motivational phase of copulatory behavior in rats
Incertohypothermic pathway
What are the function D1 and D5receptors
Increases cyclic AMP by G protein stimulatory activation of adenylyl cyclase
Action of D2, D3, D4 receptors
Decreases cyclic AMP and inhibits calcium channels
Effect f antipsychotics on non psychotic individuals
Severe EPS aka this in Sleepiness Restlessness Autonomic effects
antipsychotics that raise prolactin level
Old typiciL antipsychotics
Risperidone
Paliperidone
Cardiovascular effect of chlorpromazine and thioridazine
Orthostatic hypotension Tachycardia Abnormal ECG (thioridazine)
Antipsychotics with risk of arrhythmias
Sertindole
Ziprasidone
Quetiapine
Antipsychotics psychiatric indications
Schizophrenia Psychotic bipolar disorder Psychotic depression Treatment resistant depression Manic phase of bipolar disorder
Best treatment for catatonic schizophrenia
Benzodiazepines
Non psychiatric indications of antipsychotics
Antiemetics ( prochlorpromazine , benzquinamide because of dopamin receptor blockade )
Pruritus for h1 receptor blockade Preoperative sedatives ( promethazine )
Neuroleptanesthesia (butyrophenone
Atypical Antipsychotics with less weight gain
Ziprasidone
Only atypical antipsychotics indicated to reduce risk of suicide
Clozapine
When should you take clozapine
If failed to respond to substantial doses of conventional antipsychotic drugs
Behavioral effects of antipsychotics
Pseudodepression
Toxic confusional States
Neurological effect of antipsychotic
Extrapyramidal reactions
Tardive dyskinesia
Seizure
Agent with the least likelihood of causing tardive dyskinesia
Clozapine
quetiapine
Drugs with less potential for seizure
Risperidone Molindone Thioridazine Haloperidol Pimozide Trifluoperazine Fluphenazine
Metabolic effect of antipsychotics
Weight gain hyperglycemia hyperlipidemia diabetic ketoacidosis triglycerides HDL ratio Hyperprolactinemia 
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