Antipsychotics Flashcards
Positive symptoms of schizophrenia?
Excess of normal function • Hallucinations and delusions • Thought disorder • Perceptual disturbances • Incongruous mood • Increased motor function
**linked to overactivity of mesolimbic pathway
Negative symptoms of schizophrenia?
Decreased or loss of normal function • Blunted affect • Poverty of speech • Diminished motivation • Social withdrawal
**linked to hypoactivity or the mesocortical pathway
Cognitive symptoms?
Deficits in memory and cognitive control of behavior
What are the 4 dopamine pathways in the brain?
- mesolimbic pathway - midbrain to limbic symptom and linked to emotional benahior and hyperactivity of this pathway is thought to be associated with positive psychotic symptoms [blocking D2 receptors reduces symptoms]
- nigrostriatal pathway - substantia nigra to basal ganglia and controls motor movement [blockage of D2 receptors leads to extrapyramidal reactions – decreased movement] - dopamine inhibits GABA neurons and cholinergic excites GABA neurons - decreased dopamine neurons in parkinsons so decrease inhibition on GABA neuron thereby decreasing movement due to increased GABA neuron activity
- Mesocortical pathway - midbrain to prefrontal cortex and reduced activity of this pathway leads to the negative and cognitive symptoms [blocking D2 receptors worsens symptoms]
- tuberoinfundibular pathway - hypothalamus to anterior pituitary - dopamine inhibits prolactin secretion and when dopamine receptors are blocked prolactin levels rise leading to galactorrhea
Classical antipsychotics?
- Chlorpromazine (low potency)
- Fluphenazine (high potency)
- Haloperidol (high potency)
- Thioridazine (low potency)
high potency = more likely to produce extrapyramidal symptoms
Low potency = less likely to produce extrapyramidal symptoms but more likely to produce sedation and postural hypotension
MOA - block D2 receptors in mesolimbic pathway
Atypical antipsychotics?
- clozapine -prototype
- risperidone - causes extrapyramidal symptoms
- olanzapine
- quetiapine
- ziprasidone
- aripiprazole - partial agonist at D2 and 5HT1A as well as antagonist at 5HT2A receptors
- paliperidone - 9-hydroxyrisperidone [active metabolite of risperidone]
Higher affinities for other receptors compared to D2 receptors.
Dual antagonism at 5-HT2A and D2 receptors.
• Part of their action is due to 5HT receptor
blockade.
• Less likely to cause EPRs than classical agents.
• Less likely to cause tardive dyskinesia
• Less likely to cause increases in prolactin
• More effective at treating negative symptoms.
• Effective in refractory populations.
What receptors do clozapine and risperidone have affinity towards?
Clozapine - D1, D4, 5HT2, muscarinic and a-adrenergic recptor, AND D2
Risperidone - blocks 5HT2 more than D2
Actions of antipsychotic durgs?
- antipsychotics - reduce hallucinations and agitations creating calming effect. There is no depression of intellectual function and minimal motor incorordination
- antiemetics -with the exception of aripiprazole and thioridazine all others block D2 receptors in the trigger zone of the medulla decreasing nausea
AE effect of antipsychotics - Extrapyramidal reactions?
• Associated with high D2 potency.
• Most likely to occur with high-potency
conventional antipsychotics, such as haloperidol
and fluphenazine, that have a high affinity for
D2-receptors.
• Less likely with low-potency conventional
antipsychotic drugs such as chlorpromazine or
thioridazine.
- Dystonia (muscle spasms) - 4hrs
- Akathisia (rigidity) - 4 days
- Parkinsonism (bradykinesia) - 4 weeks
- Tardive Diskynesia - 4 months
Manage AE of Parkinsonism?
Can be treated with antimuscarinic drugs like benztropine or trihexyphenidyl with diphenhydramine or amantadine
*never use Levodopa (precursor for dopamine in parkinsons pts) with these pts as they are using them for psychosis
Manage AE of Dystonia?
May be controlled with benztropine, trihexyphenidyl or diphenhydramine
manage AE of akathisia?
Reduce dosage and add clonazepam or propranolol
How do you manage tardive dyskinesia?
Tardive dyskinesia is due to dopamine receptor up-regulation and is potentially irreversible. It is managed with discontinuing antipsychotic (or drastically reduce dose). Or if pt was taking anticholinergic drugs, stop them immediately b/c the balance b/t cholinergic an dopaminergic would be way off. Give pt diazepam and clozapine.
What is neuroleptic malignant syndrome?
Similar to serotonin syndrome and malignant hyperthermia syndrome presenting as a rare and life-threatening disorder. Pt presents with rigidity, tremor, hyperthermia, altered mental status, autonomic instability, elevated WBC and CK, and myoglobinuria. Administer Dantrolene or bromocriptine to these pts.
What is the management of sedation by antipsychotics?
This more commonly occurs with low-potency antipsychotics and atypical agents due to a blockade of central H1 receptors
