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Antidepressants & Neuroleptics Lesson 20
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Unipolar Depression n Major Depressive Disorder n Extreme sadness & despair l extent & duration important n Prevalence u females 9-26% u males 5-12% l 2:1 females ~
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MAOIs n Monoamine oxidase inhibitors u tranylcypromine (Parnate), phenelzine, (Nardil) l NE, DA, 5-HT n Dietary restrictions (Cheese Effect) l avoid foods containing tyramine l metabolism amphetamine-like u risk of cerebral hemorrhages n Many drug interactions n Overdose risk ~
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Nonselective Cyclic Antidepressants n Reuptake inhibitors l DA, NE, & 5HT l Tricyclic Antidepressants (TCA) u Imipramine, Desipramine l Tetracyclic u Maprotiline n Risk of many drug interactions (e.g., alcohol, neuroleptics, etc. ~
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NSCA: Main Side Effects n Risk of overdose n Mania or psychosis n Sedation n Anticholinergic syndrome l tremors, dry mouth, weakness, constipation, blurred vision, confusion n Impotence
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Second Generation Antidepressants
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SSRIs n Selective serotonin reuptake inhibitors l fluoxetine (Prozac, Sarafem) l sertraline (Zoloft) l paroxetine (Paxil) l citalopram (Celexa) l escitalopram (Lexapro) l fluvoxamine (Luvox) n Fewer fx on NE & DA ~
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SSRIs: Side Effects n Fewer than TCAs l lower sympathetic arousal l no anticholinergic fx n Serotonergic syndrome l GI discomfort, anxiety, restlessness, insomnia, etc. n Sexual dysfunction n Low risk of overdose n Equally effective as TCAs ~
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SSRIs: Pharmokinetics n All similar to fluoxetine (prozac) l lipid soluble l high protein binding n Half-life l 2 - 3 days l active metabolite 7 - 15 days u norfluoxetine ~
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Other Selective Reuptake Inhibitors n Norepinephrine Dopamine Reuptake Inhibitor (NDRI) l bupropion (Welbutrin) l Also tx bipolar & Smoking cessation (Zyban) n Side fx l less sexual dysfuntion than SSRI l Insomnia l seizures - 150 mg/dose limit l no subjective euphoria, abuse ~
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n Selective Serotonin Norepinephrine Reuptake Inhibitor (SNRI) l venlafaxine (Effexor) n Serotonin-2 Antagonists/Reuptake Inhibitors (SARI) l 5HT 2 –R: autoreceptor l Anxiety disorders, bulimia n Noradrenergic/Specific Serotonergic Antidepressant (NaSSA) l Mirtazapine (Remeron)~ Other Selective Reuptake Inhibitors
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Schizophrenia n Disordered thoughts & bizarre behavior l 1 percent of population l equal among sexes n Progressive l can only manage symptoms ~
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Symptoms n Positive Symptoms l Thought disorders l Delusions l Hallucinations n Negative Symptoms l Poverty of speech l Poverty of emotion l Social withdrawal ~
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Neuroleptic Drugs n Also called antipsychotics n All Effective l No abuse liability l Low overdose liability n Major side Effects: l Motor impairments l Agranulocytosis ~
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Patient Populations: Mental Institutions Thousands of patients 400 300 200 100 190019301960 1975 600 500 YEAR 1956
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First Generation Neuroleptics n Relieve only positive symptoms n Chlorpromazine (Thorazine) l phenothiazines l primarily blocks D 1 & D 2 n Haloperidol (Haldol) l butyrophenones l primarily blocks D 2 n D 2 -R affinity and clinical potency ~
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Strength of D 2 binding Therapeutic effects Hi Lo Chlorpromazine Haloperidol Spiroperidol
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1 st Generation: Pharmacokinetics n Administration l Primarily p.o.; im for rapid effects n 90-95% depot binding l liver, lungs, adrenals, spleen n Long half-life l Some metabolites active up to 3 mo. u No symptoms during this period u compliance problems ~
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Major Side Effects n Movement Effects (Extrapyramidal) l Parkinsonism l Akathisia l Tardive Dyskinesia n Agranulocytosis l white blood cells (WBC) l Not frequent, but 50% mortality ~
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Atypical Neuroleptics n Relieve negative & positive symptoms n Lower M-PAT risk l tardive dyskinesia n Atypical neuroleptics l affinity for D 2 -R l 5HT antagonism ~
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n Clozapine Clozaril l Agranulocytosis n Risperidone Risperdal l agranulocytosis; M-PAT n Aripiprazole (Abilify) l depression ~ Atypical Neuroleptics
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