Antipsychotics Flashcards
DA Hypothesis of schizo
Efficacy of pharma corresponds to drugs affinity for dopamine receptors
Drugs that increase dopamine can preceipitate psychotics symtpoms
Unmedicated schizo will have more dopamine receptors and higher levels
Negative schizo symtpoms
From dopamine deficits in HC and select cortical strcutrue
Mesolimbic/mesocortical tract
Nigrostriatal
Tuberoinfundibular
Medullary-periventricular
VTA to NA and frontal cortex…pos and neg of schizo
SN to striatal nuclei…extrapyrmaidal motor dysfunction from antipsychotics
Artcutew and periventricular neuros to pituiatyr portal…increased prolactin from anti[sychotics
Motor of vagus,a area postrema, and other BS nuclei…antiemetic effects, changes in eating behavior associated with antipsyhchotics
Most antipsychotics are
DA receptor antagonists…excpet aripirazole which is D2 partial agonist
D1 vs. D2
D1 - stimukation of cAMP and PKA dep pathways
D2 like - inhibition
Antipsychotics use
Schizo
Sedation
pReventtion of vomiting and nausea
Route of delivery of antiosychotics
Oral disintegrating
Short acting injectables (for uncoop or rapid sedation)
Long acting injectables (history of non0-adhenense)
PK of antipsychotics
Accumulate in lipid storage and released slowly
Steady state in 4 to 7 days
Long half life
CYP450s
Phenothiazines
Chlorpromazine (aliphatic) - oronal
Fluphenazine (piperazine derive)
Least potent of the typicals
Lots of sedation and weight gain
Typcal
Butyrophenones
Haloperidol
Far more potent with fewer sedation and weight gain
More extrapyramidal SEs
Most widely used
Typical
Typical antipsychotics
Good at relieving positive but not negative
Clozapine
Both pos and neg symptoms
Life threatening agranulocytosis so only use for suicide
Olanzipine, quetiapine, aripiprazole, risperidone, ziprasidone
Newer atypicals
Atypical vs typical
Atypical tx both pos and neg
Lower absolute affinity for D2 receptors relative to typical agents
Equal to greater potenc at 5-HT receptors
Fewer extrapyramidal motor symptoms
Adverse effects of antipsychotics
EPS Akathisia Tardive dyskinesia NMS Cardiac toxicity Wegith gain
EPS
Akathisia
Parkinson like syndrome…tx with anti-muscarinic drugs but NOT L-dopa
Restlessness, pacing, rocking…tx with propranolo
Tradive dyskinesia
NMS
Usually milt…intolerable TD is usually the limiting factor for antipsychotic therapy
Rigidity, fever, cog changes (neroleptic malignant syndrome)
Begin within first 2 eeeks
Tx with dantrolene
All adverse effects of antipsychotics associated with
Hypoactiviation of D2 receptors
Cardiac toxocity
Weight gain
QT prolongation (esp thiroridazine and ziprasionde)
Risk of weight gain more with atypicals like olanzapine and cloazapine
Hypotension and high resting HR
Muscarinic effects
alphra receptor blockade
mACh receptor blockade (anti-effects)
Confusion, attnetion porobs
Sedation
mACh blockade in brain
Histamine receptor blockade
Amenorrhea-galactorrhea syndrome and infertility
Blunt affect, lack of pleasure, dysphroia,
Antiemetic
In women, hyperlaction and infertility…in men loss of libido and infertiility…due to D2 blockade
DA blockade in nucleus accumbens
DA blockade in area postrema
D2 receptor signifiacne
Propentisty for alleviating positive symptoms AND causing extrapyrimdal disturbances is proportional to affinity for D2
Drugs in typical class have greater absolute affinty
Which is better and why
Depends
Atypical - fewer EP side effects but cause weight gain and variable responsiveness
Typical - less expensive
Other concenrs of antipsychotics
CYP450 problems
Compliance low
Close monnitoring
Drug abuse could exacerbate symtpms
Adjunctive therapy
Benzos
Lithium
Anticonvulsants
Prpranolo
Benzos
lithium
alleviate anxiety…side effects
Mood stabilizer
Anticonvulsatns
Propranolol
alleviate anxiety and stabilize mood..valproate preferred bc of carbamazepine intx)
Tx aggressive behaviors
