Antipsychotic Drugs Flashcards
positive symptoms
delusions
hallucinations
disorganized speech/thought
negative symptoms
anhedonia
flattened affect
apathy
primary mechanisms of antipsychotics
Blockade of dopamine (D2) receptors
- -typical agents
- -help with positive symptoms
Blockade of serotonin (5HT2) receptors
- -atypical/2nd generation
- -help with negative symptoms
how are negative symptoms relieved?
blockade of serotonin (5HT2) receptors
–atypical, 2nd gen
how are positive symptoms relieved?
blockade of dopamine (D2) receptors
–typical, 1st gen
negative symptoms due to
insufficient DA activity in mesocortical tract
positive symptoms due to
overactivity of DA activity in mesolimbic system
dopamine hypothesis
Assumes over activity of DA in mesolimbic pathway correlates with positive symptoms
-block dopamine type 2 receptors, then alleviate positive symptoms
serotonin hypothesis
Insufficient DA release at ends of neurons in mesocortical pathways correlates with negative symptoms
-less DA to interact with prefrontal cortex
- serotonin suppresses release of DA from mesocortical pathway
- block serotonin (5HT2) receptor, then take away inhibition and allow DA to be released
- alleviates negative symptoms
chlorpromazine
low potency older/typical agent
name recognition
haloperidol
high potency older/typical agent
name recognition
clozapine
most common newer/atypical agent
newer/atypical agents have a _______ potency, so they have a ________ dose
newer/atypical agents have a HIGHER potency, so they have a LOWER dose
consequences of blockage of dopamine in mesolimbic pathway
antipsychotic
-decreases positive symptoms
consequences of blockage of dopamine in mesocortical pathway
antipsychotic
-decreases negative symptoms
consequences of blockage of dopamine in nigrostriatal pathway
causes extrapyramidal movements
-Parkinson’s like symptoms
consequences of blockage of dopamine in tuberoinfundiblar pathway
causes prolactin release
- amenorrhea, galactorrhea (women)
- gynecomastia, reduced libido (men)
- fertility problems
common adverse reactions to antipsychotics
Hyperprolactinemia
-galactorrhea, amenorrhea, gynecomastia, reduced libido
Postural hypertension
-due to NE stimulating alpha-1 receptors, increasing BP
QT prolongation
-cardiotoxicity
Extrapyramidal Syndromes (EPS) -dystonias, parkinsonism
why do psychostimulants cause cardiotoxicity?
- block K+ channels
- longer ventricular repolarization
- ventricular dysrhythmia
- prolonged QT interval
how to treat extrapyramidal side effects
Lower dose of antipsychotics.
Change drug.
Drug therapy:
- benzotropine (cogentin)
- trihexyphenidyl
- ANTIMUSCARINICS
why do extrapyramidal sx occur with antipsychotics?
DA and ACh are in balance.
- if DA is blocked, then balance is tipped to favor ACh
- increased ACh = increased output to basal ganglia = EPS
Acute dystonic reaction
what is it?
Tx?
EPS related adverse effect
- oculogyric crisis
- torticollis
Tx: antimuscarinics (antihistamines) (benztropine)
tardive dyskinesia (TD)
what is it?
Tx?
- persistent EPS
- could persist rest of life
- elderly at greater risk
- use minimal doses for minimal duration
- change to atypical agent
Tx: valbenzazine (Ingrezza)
neuroleptic malignant syndrome
what is it?
Tx?
- hyperpyrexia (fever)
- rigidity
- autonomic instability
- delerium
- more likely with high doses
- rare
Tx:
- stop drug
- dantrolene, bromocriptine
what should you consider if the patient is pregnant (with antipsychotic use)?
- infant may have abnormal motor movements
- withdrawal effects
poikilothermia
- inability to control body temp
- common in low potency, older agents
- due to changes in hypothalamus
most common atypical antipsychotics
Clozapine Risperidone Olanzapine Quetiapine Aripiprazole
- newer
- more expensive (even the generic)
adverse effects of atypical antipsychotics
- increases in weight, blood glucose, and lipids
- orthostasis (alpha-receptor blockade)
- others: somnolence, dizziness, inc LFTs, CYP450 interactions)
- EPS is LESS likely to occur
- –decreased prolactin disturbances
clozapine
role?
adverse effects?
- atypical, newer
- most effective antipsychotic
- seldom used
- least likely to develop EPS
Adverse Effects
- sedation
- weight gain
- sialorrhea (xs saliva)
- seizures (rare)
- agranulocytosis (v rare, but super serious)
time to effect for antipsychotics
- most sx improve slowly
- higher potency = higher response
duration of treatment for antipsychotics
- most require prolonged maintenance
- rebound effect if abruptly stopped
maintenance is the best efficacy, but due to illness are likely not to be continued
receptor blockade of typical vs atypical antipsychotics
TYPICAL: D2 > 5HT2A
ATYPICAL: 5HT2A > D2
effectiveness of typical vs atypical antipsychotics
TYPICAL: mainly for positive symptoms
ATYPICAL: both positive and negative symptoms
movement disorders of typical vs atypical antipsychotics
TYPICAL: more
ATYPICAL: less
metabolic effects of typical vs atypical antipsychotics
TYPICAL: less
ATYPICAL: more
consequences of blocking alpha-1 receptor
orthostasis
consequences of blocking dopamine-2 receptor
extrapyramidal movements
consequences of blocking histamine-1 receptor
sedation
weight gain
consequences of blocking muscarinic receptor
dry mouth, blurred vision, urinary retention, constipation
class wide safety concern for antipsychotics
eldery patients with dementia-related psychosis is treated with antipsychotic drugs are at an increased risk of death compared to a placebo
- more pleasant with antipsychotic, easier to treat
- may shorten life
drug-induced psychoses can be commonly caused by which drugs?
anticholinergic drugs benzodiazepines antipsychotic agents dopaminergic agents corticosteroids withdrawal from sedatives/alcohol
