Antipsychotics Flashcards
what is schizophrenia?
chronic psychotic disorder c:
- disturbed behavior
- thinking
- emotions
- perceptions
what are some schizo (+) sx’s?
- hallucinations/delusions
- thought disorder
- perceptual disturbances
- incongruous mood
- increased motor function
what are some schizo (-) sx’s?
- blunted affect
- poverty of speech
- diminished motivation
- social withdrawal
what are some cognitive sx’s of schizo?
deficits in memory and cognitive control of behavior
schizo (+) sx’s biological basis?
linked to overactivity of mesolimbic pathway.
Schizo (-) and cognitive sx’s biological basis?
hypoactivity of the mesocortical pathway
what is the dopamine hypothesis of schizo?
excessive dopaminergic activity plays a role.
rx’s increase activity = increase/produce (+) psychotic sx’s
- ex) amphetamine and cocaine
rx’s decrease activity = decrease/stop (+) sx’s.
what are 4 well-defined dopamine pathways in the brain?
- mesolimbic pathway
- nigrostriatal pathway
- mesocortical pathwya
- tuberoinfundibular pathway
describe mesolimbic pathway
midbraine to limbic system.
role: emotional behaviors
hyperactive = (+) psychotic sx’s
block D2 receptors = antipsychotic effects
describe nigrostriatal pathway
substantia nigra to basal ganglia
role: controls motor movements
block D2 recpetors = disorders of movement can appear
part of extrapyramidal nervous system.
- blck dopamine recpetors can give motor a.e AKA extrapyramidal rxns.
describe mesocortical pathway
midbrain to prefrontal cortex.
reduce activity = (-) and cognitive sx’s.
block D2 recptors = cause/worsen sx’s
Describe tuberoinfundibular pathway
hypothalamus to anterior pituitary.
dopamine released from these neurons inhibits prolactin secretion.
when blocked = prolactin level rise, can cause galactorrhea.
what are some classical antipsychotic drugs?
- chlorpromazine
- fluphenazine
- haloperidol
- thioridazine
what are some atypical antipsychotic drugs?
- clozapine
- risperidone
- olanzapine
- quetiapine
- ziprasidone
- aripiprazole
- paliperidone
what are HIGH potency classical antipsychotic drugs?
- fluphenazine
2. haloperidol
what are LOW potency classical antipsychotic drugs?
- chlorpromazine
2. thioridazine
- chlorpromazine
- fluphenazine
- haloperidol
- thioridazine
MOA?
block D2 receptors in the mesolimbic pathway
what are atypical antipsychotics drugs?
they have higher affinities for other receptors than D2 receptors
ex)
- clozapine: high affinity for D1, D4, 5HT2, musc, and a-adrenergic
- risperidone: 5HT2
what are some common properties of atypical antipsychotics?
- dual antagonism at 5HT2A and D2
- part of action is d/t 5HT block
- less likely to cause EPRs than classical agents
- less likely to cause tardive dyskinesea
- less likely to cause increases prolactin
- more effective at treating (-) sx’s
- effective in refractory populations
properties of clozapine?
prototype of the atypical agents
properties of risperidone?
causes EPR, rare at therapeutic doses
properties of paliperidone?
9-hydroxyrisperidone, active metabolite of risperidone
properties of aripiprazole?
partial agonist at D2 and 5HT1A
antagonist at 5HT2A
what are two atypical antipsychotics least likely to induce EPR?
- clozapine
2. quetiapine
antipsychotics actions?
- reduce hallucination/agitation
- calming effect
- don’t depress intellectual function
- motor incoordination is minimal
- onset is
antipsychotics antiemetic effects?
block D2 receptors of the chemoreceptor trigger zone in the medulla.
exceptions: aripiprazole and thioridazine (no antiemetic)
antipsychotic metabolisM?
CYP2D6, CYP1A2, CYP3A4
don’t interfere c the metabolims of other drugs.
causes of antipsychotic extrapyramidal rxns?
- assoc c high D2 potency.
- rx: haloperidol and fluphenazine
less likely with:
- low D2 potency: clorpromazine or thioridazine
- strong anticholinergic: thioridazine and chlorpromazine
- atypical antipsychotics
what are some Extrapyramidal rxns?
- parkinsonism
- dystonia
- akathisia
tx for parkinsonism?
antimuscarinics:
- benztropine
- trihexyphnidyl
- diphenhydramine
- amantadine
Levodopa should never be used in these pts.
tx for dystonia?
- benztropine
- trihexyphenidyl
- diphenhydramine
tx for akathisia?
- reduction of dosage or change rx
- clonazepam
- propranolol.
what is tardive dyskinesia?
late-occuring syndrome of abnl chreoathetoid movements.
unwanted effect of antipsychotics
potentially irreversible
may be d/t dopamine receptor up-regulation
management of tardive dyskinesia?
- d/c or reduce rx.
- eliminate all rx’s c central anticholinergic action (antiparkinsonian and TCAs)
- diazepam
clozapine is rec’d for pts c tardive dyskinesia who require antipsychotics.
what is neuroleptic malignant syndrome?
rare and life-threatening disorder.
- rigidity, tremor, hyperthermia
- altered mental status
- autonomic instability
- elevated WBC and CK
- myoglobinemia c potential nephrotoxicity
tx of neuroleptic malignant syndrome?
- dantrolene
2. bromocriptine
what antipsychotics cause sedation?
low-potency and atypical agents
d/t block central H1 receptrs.
which antipsychotics cause seizures?
- chlorpromazine
2. clozapine
how can antipsychotics produce autonomic effects?
block musc receptors, producing anticholinergic effects.
- block alpha1 receptors = orthostatic hypotension, impaired ejaculation.
which antipsychotics cause toxic and allergic rxns?
clozapine causes agranulocytosis
regular blood cell counts are mandatory.
what are some endocrine and metabolic effects c antipsychotics?
- prolactin secretion (less c atypical)
- block D2 recpetors in pituitary.
- women: amenorrhea-galactorrhea, infertility
- men: loss libido, infertility and impotence - weight gain
- majority atypical
which antipsychotics cause high incidence of cardiac toxicity?
- thioridazine (QTc- and T-wave changes)
2. ziprasidone (prolong QTc)
which antipsychotics cause ocular complications?
- chlorpromazine - deposits in corean and lens.
2. thioridazine - retinal deposits.
what are some psychiatric indications for antipsychotics?
- schizo
- bipolar
- suppression of tics in tourretts
- control disturbed behavior in alzheimers
- adjuncts to antidepressants in tx-resistant major depression.
- combo c antidepressants in psychotic depression
- irritability assoc c autism (DOC risperidone)
what are some non-psychiatric indications for antipsychotics?
- nausea and vomiting
2. droperidol is used in combo c fentanyl in neurolept-anesthesia
what are DOC for antipsychotics?
- atypical preferred d/t:
- benefit (-) sx’s and cognition
- diminished risk of EPRs and tardive dyskinesia
- lesser increase in prolactin levels. - risperidone - most prescribed
- clozapine - d/t potential for agranulocytosis is reserved for refractory pts.
antipsychotic in pregancy?
cat C
clozapine is catB
risks (greater c atypicals):
- hyperglycemia
- weight gain
define psychosis?
sustained mental state of impaired contact c reality
