Term
|
Definition
-only 20% have their symptoms stopped
-2/3 gain some relief
-the rest are unresponsive |
|
|
Term
|
Definition
-DIVERSE group
-tx of symptoms
-typicals and atypicals |
|
|
Term
|
Definition
-treat positive symptoms
-primary action is D2 receptor block (70-80%)
-blockade of D2 receptors in mesolimbic pathway to treat symptoms, blockade in other pathways causes SE |
|
|
Term
|
Definition
-TREAT POSITIVE AND NEGATIVE SYMPTOMS
-1st line
-lower affinity for D2 receptor (40-60% block)
-block 5-HT2A receptors (70-90%)
-heterogenous group |
|
|
Term
| antipsychoitcs used to treat |
|
Definition
-schizo
-bipolar affective disorder
-control agitation or psychosis in severely depressed
-nausea |
|
|
Term
| adverse effects of antipsychotics on movement (EPS) |
|
Definition
-parkinsonism
-dystonia
-akathisia
-acute and tardive dyskinesia |
|
|
Term
|
Definition
-akinesia
-rigidity
-tremor |
|
|
Term
|
Definition
-involuntary sustained muscle contractions
-twisting and repetitive movements or abnormal postures |
|
|
Term
|
Definition
|
|
Term
| acute and tardive dyskinesia |
|
Definition
-impairment of voluntary movement
-mouth, lips, tongue, (rabbit like movements)
-neck, chest, trunk |
|
|
Term
| antipsychoitc effect on DA neurons? |
|
Definition
|
|
Term
|
Definition
-late onset unlike other antipsychotic induced movement disorders
-random movements of tongue lips jaw face arms swaying of trunk or hips
-due to prolonged exposure to D2 antagonists
-results in UPREGULATION OF D2 receptors in nigrostriatal pathway
-"dopamine hypersensitivity"? |
|
|
Term
| more adverse SE of antipsychotics |
|
Definition
-DUE to D2 blockade
-neuroleptic malignant syndrome
-hyperprolactinemia |
|
|
Term
| neuroleptic malignant syndrome |
|
Definition
-unpredictable, develops rapidly
-low incidence but high mortality
-extreme rigidity
-fever over 104
-autonomic disturbances
-muscle destruction |
|
|
Term
|
Definition
-causes swollen breasts and milk production (men and women)
-antipsychotics also block release of FSH and LH (no menstruation or ovulation in women)
-pseudopregnancy |
|
|
Term
|
Definition
-D2 blockade leads to movement disorders
-5-HT2A blockade inc DA |
|
|
Term
| primary site of action typical |
|
Definition
| -nigrostriatal and mesolimbic |
|
|
Term
| primary site of action of atypical |
|
Definition
| mesolimbic and mesocortical |
|
|
Term
|
Definition
-high DA in schizo
-D2 blockade relieves positive symptoms
-5HT2A blockade does not inc DA significantly, relief of positive symptoms |
|
|
Term
|
Definition
-low DA in schizo
-D2 blockade worsens negative symptoms and cognition
-5HT2A blockade inc DA and improves negative symptoms |
|
|
Term
| summary tuberoinfundibular |
|
Definition
-normally DA inhibits prolaction
-D2 blockade leads to hyperprolactinemia, sexual dysfunction, dysmenorrhea
-5HT2a blockade does not inc DA significantly (may still get with atypicals) |
|
|
Term
| even more adverse SE of antipsychotics |
|
Definition
-not due to D2 blockade
-WEIGHT GAIN AND METABOLIC SE
-sedation
-orthostatic hypotension
-anticholinergic SE
-seizures
-jaundice
-dermatitis
-photosensitivity |
|
|
Term
| other receptors antipsychotics bind |
|
Definition
-responsible for SE
-do not know if blockade of these receptors contributes to alleviation of symptoms
-muscarinic
-alpha adrenergic receptors
-H2 histamine receptors |
|
|
Term
| binding to muscarinic receptors causes |
|
Definition
| -dry mouth, blurred vision, urinary retention , constipation |
|
|
Term
| binding to alpha adrenergic receptors |
|
Definition
|
|
Term
| binding to H2 histamine receptors causes |
|
Definition
|
|
Term
|
Definition
-long clinical duration, need to be careful why?
-most highly lipid soluble
-F is 25-65%
-highly protein bound (92-98%)
-high Vd (greater than 7 L/kg)
-multiple metabolic pathways
-slow elimination (10-20hrs) |
|
|
Term
|
Definition
|
|
Term
| multiple metabolic pathways |
|
Definition
-sulfoxidation, N-dealkylation, hydroxylation, glucuronidation
-typicals are most commonly metabolized by CYP2D6
-metabolites are often active (Paliperdone is active metabolite of risperidone) |
|
|
Term
| careful when giving CYP inducers and inhibitors and |
|
Definition
|
|
Term
| antipsychotic drug interactions |
|
Definition
-addictive effects with:
-SSRIs (inc EPS)
-sedatives
-anticholinergics
-antihistamines
-alpha-AR blocking drugs
-drugs with quinidine-like action (thioridazine and ziprasidone)
-antiarrhythimic drug blocks NA channels and PROLONGS QT interval |
|
|
Term
|
Definition
-(phenothiazines)
-aliphatic
-piperidine
-piperazine |
|
|
Term
|
Definition
-thioxanthenes (thiothixene)
-butyrophenones (HALOPERIDOL)
-heterocyclics (OLANZAPINE, QUETIAPINE, RISPERIDONE) |
|
|
Term
| chemistry of antipsychotics |
|
Definition
| -differeing structures but all can adapt to a conformation similar to DA |
|
|
Term
| why do antipsychotics bind to other receptors? |
|
Definition
|
|
