Flashcards in Antipsychotics Deck (24):
What is the age of onset of SZP (schizophrenia) in males? females?
males: 15-24 years
What are positive sx of SZP?
hallucinations, delusions, disorganized speech ---considered excess cognition
What are negative sx of SZP?
avolition (lack of motivation), alogia (slowed speech), anhedonia(lack of pleasure), blunted effect
---- considered deficits in behaviour
What are the cognitive sx of SZP?
- decline in attention, language, memory, executive function
What are affective sx of SZP?
- blunted, inappropriate expression
- often leads to social stigma
What is the dopamine hypothesis?
- that there is too much mesolimbic DA pathway activity, leading to the presence of positive sx
- negative sx occur from low dopaminergic activity in the mesocortical pathway
What is the pathway of positive sx for dopamine?
ventral tegmental area -> D2 travels down the mesolimbis system-> goes to the nucleus accumbens-> centre for motivation, reward, addiction and reinforcing behaviour
What is the pathway for negative symptoms for dopamine?
ventral tegmental area-> D1 goes down the mesocortical system -> goes to the prefrontal cortex-> centre for cognition, communication, social function and stress response
What do most antipsychotics strongly block?
D2 dopamine receptors
Drugs that increase what can induce psychosis?
What is the action of typical antipsychotics?
MOA thought to be antagonism of D2 receptors in the mesolimbic pathway
- causes effective relief of positive symptoms
What are the typical antipsychotics?
- chlorpromazine, fluphenazine, haloperidol, thiothixene
What are the adverse effects of typical antipsychotics related to?
- receptor non-selectivity
- blockade of non-mesolimbic D2 dopaminergic pathways
Examples of receptor non-selectivity
- chlorpromazine: alpha 1 adrenergic, 5HT2, D2, D1, muscarinic, etc
- haloperidol: D2, D2, alpa 1, 5HT2, muscarinic, etc
-- result of this is mild to severe.. toxic confusional state, dry mouth, urinary retention (antimuscarinic)
- orthostatic hypertension, dizziness, tachycardia (a1- adrenergic blockade)
- weight gain and sedation: histamine blockade
What is the nigrostriatal pathway?
- blockade of D2 from the substantia nigra to the stria terminals
- this causes a blockade of the coordination of voluntary movement
- can cause parkinson, akathisia, acute dystonic reactions, and tardive dyskinesia
What is the tuberoinfundibular pathway?
- blockage of D2 from the hypothalamus to the pituitary gland- increases prolactin production
- in women: this can cause lactation, amenorrhea, infertility
- in men: this can cause lactation, impotence,decreased libido
What are some other common side effects of antipsychotics?
- pseudo depression related to drowsiness
- corneal and lens deposits
- retinal deposits
-cardiac arrythmias in overdose
- neuroleptic malignant syndrome (severe muscle rigidity, impaired sweating, fever, autonomic instability, severe agitation)
What are the advantages of using atypical antipsychotics?
- blocks D2 in the nucleus accumbent, but also..
- has a reduced D2 affinity: nigrostiatial= decrease in EPS
- blocks 5HT receptors- decreases negative symptoms
What does increasing the serotonin affinity do?
- decreases negative sx by increasing mesocortical dopamine
Examples of antipsychotics
- risperidone (D2=5HT receptor potency)
- olanzapine (5HT>D2 , also D1)
-quetiapine (D2= 5HT)
-clozapine (D4= 5HT)
- ariprazole (D2 partial agonist, 5HT agonist)
What are the adverse effects of atypical antipsychotics?
- same as typical antipsychotics, with lower risk, especially go EPS
- weight gain, hyperlipidemia, hyperglycaemia associated with 5HT blockage - clozapine and olanzapine
- higher death rates in patients with dementia
What are the main drug interactions?
- excess sedation: anxiolytics, alcohol. antidepressants, antihistamines
- additive antimuscarinic effects
- metoclopramide: D2 antagonist, EPS
- SSRI antidepressants: dopamine suppression in NGS, and EPS
How do typical antipsychotics work?
- they block D2 in the mesolimbic (decreases + symptoms), nigrostriatal (EPS) and tuberoinfundibulnar (hyperprolactin) pathways