Final: Antipsychotic Drugs Flashcards
extreme form of slowness/absence of motor movements and affective indifference
neurolepsis
drugs that produce neurolepsis
neuroleptics (aka antipsychotics)
examples of classical neuroleptics
phenothiazines (chlorpromazine)
butyrophenones (haloperidol)
second generation (atypical antipsychotic) examples
clozapine
risperidone
aripiprazole
do classical or atypical antipsychotics produce less side effects
atypical antipsychotics
law of thirds
1/3: patients respond well
1/3: show significant improvements but may relapse
1/3: fail to respond
why are antipsychotic drugs considered “dirty”
they have binding affinity for MANY different neurotransmitter systems
-can be good bc indirectly treating many issues BUT can have wide range of side effects
antipsychotic actions are attributed to what neurotransmitter system
dopamine D2 receptor antagonists
where are the D2 receptors located
basal ganglia, Nacc, amygdala, hippocampus, cerebral cortex
ROA antipsychotics
oral - most common
IV or IM injections - more common when sedation is the goal
depot injection
high concentration of lipid soluble drug dissolved in oil and injected into muscle
- slow diffusion from oil into body fluids over long period of time
- single injection can last up to 4 weeks
absorption of antipsychotics
most readily absorbed in GI tract
many do first pass metabolism
bioavailabilty 25-65%
distribution of antipsychotics
placenta and BBB
high depot binding: blood protein and in body fat
- released slowly
injections can take weeks to reach steady state
ex: risperidone - 28 days
metabolism of antipsychotics
LIVER cytochrome p450s
- most have inactive metabolites
- considerabe individual varieties
- interact with antidepressants, anxiolytics due to competition
excretion of antipsychotics
- due to high depot binding - long half life - metabolites found in urine for months
- atypical excreted quicker - less depot binding since less lipophillic
neuroleptic induced deficit syndrome
D2 receptor antagonists
blocking mesolimbic D2 receptors causes apathy, anhedonia, loss of motivation
-worsening negative symptoms
dec Da - neg symptoms
mesocortical DA system in Scz
dec activity - cognitive deficits and flat affect
can worsen cognitive ability by exaerbatig DA signaling defiicts in cortex
nigrostriatal Da in Scz
substantia nigra - striatum
- movement
extrapyramidal symptoms (EPS): involuntary changes in motor ability resulting from classical antipsychotic drug treatments (akathisia, dystonia, PD, tardive dyskinesia, blockage of nigrostriatal D2
akathisia
restlessness
dystonia
sustained muscle contractions
tardive dyskinesia
cannot stop moving - only chronic treatment
acute D2 receptor antagonism
blocking D2 receptors in nigrostriatal pathway can cause a drug-induced parkinsonism
chronic D2 receptor antagonism
chronic D2R blockade causes compensatory changes in dopamine system
tardive dyskinesia inc with duration of treatment
tuberoinfundibular dopamine system in Scz
within hypothalamus
regulates pituitary hormone secretion/neuroendocrine effects
blocking D2 receptors impairs function
- excessive prolactin secretion, inhibition of growth hormone
-dec sex drive, no menstruation, breast tissue growth
-neuroleptic malignant syndrome
neuroleptic malignant syndrome
life threatening
fever, rigidity, altered consciousness, ANS instability
side effects if antipsychotics
depend on what receptor the drug binds to
- blocking cholinergic - dry mouth, blurred vision, difficulty urinating, GI problems
- anti-adrenergic: dizziness, faintness, blacking out
- sedation
DA D2R antagonism is paired with what other antagonism
5-HT2A
together they help treat psychosis
5-HT2AR antagonism stimulates DA release to reduce side effects
- reduces EPS from nigrostriatal pathway
- reduces neg symptoms and improves mood by inc DA in PFC
- reduces prolactin release from hypothalamus
atypical antipsychotica
reduce positive symptoms without causing EPS or side effects
- selective D2 receptor antagonists
- DA partial receptor agonists
- broad spectrum antipsychotics block other receptor types in addition to D2 receptors
selective D2 receptor antagonists
- high affinity for D2 receptors, slight for D3
- effects on ANS and cardiac mild
- BUT: hormonal side effects and risk of fatal blood disorders reduces their use
dopamine system stabilizers - atypical antipsychotics
partial DA agonists compete with DA for receptors and reduce DA effect
- inc DA in PFC while also reducing DA in mesolimbic pathway
ex: aripiprazole (ABlilify) - partial agonist with low side effects
clozapine
broad spectrum antipsychotics
-weak affinity for D1 and D2, strong affinity for adrenergcm seretonergic, muscarinic, histaminergic, and D4
effective for people not responding to typical neuroleptics
reduces some neg and cognitive symptoms but many side effects due to action on multiple receptors
other conditions treated by antipsychotics
- disorders with excess DA (Tourette’s, Huntington’s)
- powerful antiemetics: useful for motion sickness
- chronic pain
- hiccups, stuttering, delirium tremens, drug-induced psychosis
what other diseases are atypicals used for we already learned about
MDD, bipolar disorder, mania, irritability in autistic children
