antipsychotic drugs Flashcards
define psychosis
- denotes a variety mental disorders with multiple caues and manifestations
- Severe psychiatic disorders cahracterized by distrubances in behavior and though processing (delusions and halucinations)
describe the possitive and negative symptoms of schizophrenia
Positive
–> delusions, hallucinations, agitation, paranoia, aberrant thinking, intrusions of thoughts
negative
–> emotional aptahy (flat affect)
–> socially withdrawn
–> inattentiveness
describe teh dopamine hypothesis of schizophrenia
- hyperactivity of the mesolimbic/mesocortical DA system
-_-> EXCESSIVE LIMBIC DA ACTIVITY –> PSYCHOSI_S
- some antipsychotic drugs STRONGLY BLOCK D2 RECEPTORS
–> research shows DA levels and D2 receptor density is increased in schizophrenic brains
**not perfect theroy –> doesn’t explain cognitive impairement
describe serotonin hypothesis in schizophrenia
- blockade of 5HT2a receptor is key mech of action of main classes of atypical antipsychotic drugs
- many ATYPICAL agets also block 5HT2C receptors (inverse agonists)
Describe glutamate hypothesis schizophrenia
- phencyclidine and ketamine (NMDA inhibitors) can exacerbate both cognitive impairments and psychosis in schizophrenia pts
- HYPOFUNCTION OF NMDA receptors located on GABAergic interneurons –> can lead to hyperstimualtion of cortical neruons
What are some therapeutic indications for antipsychotic agents
- schizophrenia
- psychotic behavior (depression, bipolar etc)
- Severe mania (manic phase of bipolar)
- antiemetic (prochlorperazine, phenergan)
- hiccough (hiccups)
- Chronic neuropathic (central) pain syndromes
- Tourett’s syndrome
what is the most efficacious tx
- Drug + social therapy has the lowest percent of rehospitalizations
List the typical antipsychotics
- chlorpromazine
- thioridazine
- fluphenazine
- haloperidol (haldol)
List the atypical antipsychotics
- clozapine
- olanzapine
- resperidone
- aripiprazole
- quetiapine
- ziprasidone
Reasons people stop antipsychotic medications
- lack efficacy
- lack of disease insight
- unwillingnes to tolerate side effects
- wieght gain
- extrapyramidal side effects
- sedation
- sexual side effects
Describe risk of Extrapyramidal sydrome
- typcal neuroleptics
–> strongly associated with EPS
- Atypical agents
–> risperidone most strongly assocaited with EPS
–> Clozapine and quetiapine LEAST strongly associated with EPS
- EPS risk influenced
–> rapid dose escalation, TARGET DOSE, patient vulnerability
Antipsychotic agents MoA
- DOPAMINE RECEPTOR ANTAGONIST
–> most at post-synaptic D2 receptors
- ATYPICAL AGENTS (clozapine)
–> antagonist at 5HT2a receptors and D2 receptors
describe Extrapyramidal syndrome (EPS)
- Parkinson-like syndrome = rigidity, tremor, bradykinesia
- Akathesia = motor restlessness and anxiety
- Dystonia
- Tardive dyskinesia = involuntary movements of tongue, mouth, face and head (increases with age of pts)
–> GENERALLY IRREVERSIBLE
Antipsychotics on mesolic-mesocortical
- VTA –> limbic system and neocortex
- related to behavior and psychosis
antipsychotic drugs on nigrostriatal
- SN –> dorsal striatum
- coordination of volunatary movement
- blockade of D2 rec. responsible for EPS
antipsychotics drugs on tuberoinfundibular and medullary periventricular area
- Tuberoinfundibular
–> inhibition of prolactin secretion form anterior pituitary
- medullary periventricular area
–> chemoreceptor trigger zone (CTZ, area postrema)
–> Eating behavior
what are some the anti-dopaminergic effects of antipsychotics
- Nausea and vomting (antiemetic
- Endocrine
–> HYPERPROLACTINEMIA (decreased testosterone, gynecomastia, changes in libido, galactorrhea and infertility
- Weight gain
–> DA, or H1 mech
–> CLOZAPINE and OLANZAPINE
pharmacologic effects of Antipsychotics
- Anti-cholinergic effects
–> urinary retention, dry mouth, blurred vision, constipation, mental confusion
- Anti-histamine (H1)
–> sedation, weight gain
- Anti-adrenergic (PRIMARILY ALPHA1)
–> postural hypotension, reflex tachycardia, erectile dysfunction and impaired ejaculation
antipsychotic adverse effects
- Hepatic dysfunction (obstructive jaundice - phenothiazine)
- Uticaria and photosensitivity (phenothiazines)
- Ocular opacity (phenothiazines)
- cardiac conduction defects
- blood disorder (clozapine)
- Decreased seizure threshold
