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42 Cards in this Set
- Front
- Back
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Overview |
Schizophrenia most common -Affects 1% of pop. (300k acute episode annually) -25-50% of schizo, attempt suicide, 10% succeed -20% SS benefit used for Schizo pts -Direct and Indirect costs billions |
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Paranoid Psychosis |
-Delusional beliefs -Hostile Belligerence -Grandiose Expansiveness |
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Depressive Psychosis |
-Retardation and apathy -Anxious self-punishment and blame |
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Disorganized-Excited Psychosis |
-Conceptual disorganization -Disorientation -Excitement |
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Define: Schizophrenia |
2 or more for Diagnosis: 1. Delusion 2. Hallucintions 3. Disorganized Speech 4. Grossly disorganized or catatonic behavior
-Social function decrease compared to pre-symptomatic levels. (Work, relationships, self-care)
-Affective disorders/Alcohol/drug abuse must be ruled out |
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Symptoms of Schizo |
Five subcategories 1. Postive 2. Negative 3. Cognitive 4. Agressive/Hostile 5. Depressive/Anxious
-Can treat positive, others harder |
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Positive symptoms of Schizo |
-Delusion -Hallucination -Distortions in language -Disorganized speech -Disorganized behavior -Agitation -Catatonic behavior |
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Negatie Symptoms of Schizo |
-Blunted effect -Emotional Withdrawal -Poor rapport -Passivity -Alogia -Avolition -Anhedonia (can't feel pleasure) -Attentional impairment |
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Antipsychotic dose vs D2 Affinity |
Higher Dose = Lower Affinity for D2 |
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Biological Basis of Schizophrenia |
-Exact cause unknown (genetic component) -DA plays key role in hypothesis
4 DA pathways 1. Mesolimbic 2. Mesocortical 3. Nigrostriatal 4. Tuberoinfundibular |
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DA Path- Mesolimbic |
VTA to axons in limbic area -CNS Stimulants -Hyper activity accounts for positive psychotic symptoms -Too much DA accounts for SX |
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DA Path - Mesocortical |
VTA to axons in cortical area -negative symptoms and some cognitive symptoms -Too much DA accounts for SX |
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DA Path - Nigrostriatal |
Substantia nigra to axons in caudate and putamen
-Deficiency cause movement disorders (parkinsons) -Hyperactivity accounts for hyperkinetic movement (tics/ dyskinesia) |
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DA Path - Tuberinfundibular |
Thalmus to anterior pituitary -Inhibits prolactin -Hyper activity counts for sexul dysfunction |
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Phenothiazines |
-Created Diphenhydramine -Chlorpromazine --Prototype for typical antipsychotics --developed by accident. --EPS***, sedation, anticholinergic |
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Why do phenothiazines work? |
-Structural similarity to DA -Optimal side chain length is 3 -Antagonist (larger than agonist) -Mixed pharmacology (antipsycotic. cholinergic, histamine) |
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Neuroleptics |
Rauwolfia serpentina alkaloids -Reserpine --Rarely used |
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Side effects of Typical |
-EPS*** -PiperiZINE more potent than piperiDINE -Sedation -Antichol -Ortho hypo -NO/Minimal Weight Gain |
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Side effects of Atypical |
-Lower EPS -Weight GAIN -some antichol, ortho hypo, sedation
-Quetiapine is Go to |
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Phenothiazines |
Chlorpromazine -has Cl withdrawing group
Thioridazine -S-Me is donating (becomes sulfoxide) -Piperidine side chain. (Conformational constrain) |
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Phenothiazines cont'd |
Compazine Perphenazine Trifluoperazine Fluphenazine
Electron withdrawing (F, Br, CN, NO2) Want Tertiary amine -Hydroxy ethyl terminal can extend T1/2 |
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Metabolism of Chlorpromazine |
Has Many metabolites -Some active -Some inactive -All chlorpromazine like compounds undergo similar metabolism |
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Thioxanthenes |
Thiothixene |
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Geometry note |
-Cis (Z) Active (goes right) -Trans (E) Inactive (goes left) |
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Phenylbutylpiperidines (butyrophenones) |
-Haloperidol -Droperidol (antiemetic generally)
D2 antagonists -Typically has EPS |
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Haloperidol Dyskinesia (toxicity) |
MAO converts Haloperidol to MPP+ like structure
-This does not occur with chlorpromazine compounds |
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Haloperidol Metabolism |
Ketone reduces to hydroxyl
Or N-Deakylation (split in two pieces) |
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Phenylbuytlpiperidine (diphenylbutylpiperidine) |
Pimozide -Similar to haloperidol |
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Dihydroindolones |
Molindone -D2 antagonist |
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Dibenzapines (dibenzodiazepine) |
Clozapine -Angranulocytosis (1% of pop.) -Available as ODT |
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Dibenzepines (thienbenzodiazepine) |
Olanzapine -Combined with fluoxetine for bipolar -Thiophene ring -Less toxic |
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Dibenzepines (dibenzothiazepine) |
Quetiapine -Aeromatic hydroxylation occurs -Has No Cl group -Allylic tail OH oxidized to COOH which does not cross BBB |
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Benzisoxazole |
Risperidone -DA and 5-HT2 antagonist -Inj/ODT
Paliperidone -Metabolite of risperidone
Ziprasidone
Iloperidone -Mixed DA/5HT2 antagonist |
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Benzisoxazole |
Lurasidone -Don't used with Cyp 3A4 inhibitor -Not approved in dementia psychosis |
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Quinolone |
Aripiprazole -Partial Agonist at DA receptor -Function as antagonist when endogenous present -Limited EPS -Limits overactivity -Functionally selective -Antidepressant combo = faster action |
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Dibenzoxepine |
asenapine -Text book has metabolism LEARN IT -SL administration -Bipolar and Schizo use -Atypical |
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Lithium Carbonate (Li2CO3) |
-Manic depressive/Bipolar -Mechanism unclear |
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Divalproex Sodium (depakote) |
Valproic acid = 2-n-propylpentanoic acid -Manic episodes in bipolar -Lower Peaks and valleys in manic pt's |
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mGlu2/3 Receptor Agonist |
LY2140023 (clinical trials) -Similar to olanzapine -No weight gain -No prolactin Elevation -No EPS -Prodrug |
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Affinity for receptors... noted |
Side effects: Sedation: antagonism of H1 Ortho Hypo: antagonism of Adrenergic -Anticholinergic: Antagonism at muscarinic |
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Long acting neuroleptic |
Ester moeity at allyl tail allows for long duration of action
-Inject once a month |
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SAR for Chlorpromazine like |
1. Must have Electron withdrawing group 2. 3 Carbon Side Chain 3. Tertiary amine |
