Antipsychotics PDF

PSYCHIATRY ` PSYCHIATRY!PHARMACOLOGY SEC TION III 591 Antipsychotics Typical (1st-generation) antipsychotics—haloperidol, pimozide, tri!uoperazine, !uphenazine, thioridazine, chlorpromazine. Atypical (2nd-generation) antipsychoti...

PSYCHIATRY ` PSYCHIATRY!PHARMACOLOGY SEC TION III 591 Antipsychotics Typical (1st-generation) antipsychotics—haloperidol, pimozide, tri!uoperazine, !uphenazine, thioridazine, chlorpromazine. Atypical (2nd-generation) antipsychotics—aripiprazole, asenapine, clozapine, olanzapine, quetiapine, iloperidone, paliperidone, risperidone, lurasidone, ziprasidone. MECHANISM Block dopamine D2 receptor ( cAMP). Atypical antipsychotics also block serotonin 5-HT2 receptor. Aripiprazole is a D2 partial agonist. CLINICAL USE Schizophrenia (typical antipsychotics primarily treat positive symptoms; atypical antipsychotics treat both positive and negative symptoms), disorders with concomitant psychosis (eg, bipolar disorder), Tourette syndrome, OCD, Huntington disease. Clozapine is used for treatment- resistant psychotic disorders or those with persistent suicidality (cloze to the edge). ADVERSE EFFECTS Antihistaminic (sedation), anti-!1-adrenergic (orthostatic hypotension), antimuscarinic (dry mouth, constipation) (anti-HAM). Use with caution in dementia. Metabolic: weight gain, hyperglycemia, dyslipidemia.  risk with clozapine and olanzapine (obesity). Endocrine: hyperprolactinemia Ž galactorrhea, oligomenorrhea, gynecomastia. Cardiac: QT prolongation. Neurologic: neuroleptic malignant syndrome. Ophthalmologic: chlorpromazine—corneal deposits; thioridazine—retinal deposits. Clozapine—agranulocytosis (monitor WBCs clozely), seizures (dose related), myocarditis. Extrapyramidal symptoms—ADAPT: ƒ Hours to days: Acute Dystonia (muscle spasm, stiffness, oculogyric crisis). Treatment: benztropine, diphenhydramine. ƒ Days to months: ƒ Akathisia (restlessness). Treatment: -blockers, benztropine, benzodiazepines. ƒ Parkinsonism (bradykinesia). Treatment: benztropine, amantadine. ƒ Months to years: Tardive dyskinesia (chorea, especially orofacial). Treatment: benzodiazepines, botulinum toxin injections, valbenazine, deutetrabenazine. NOTES Lipid soluble Ž stored in body fat Ž slow to be removed from body. Typical antipsychotics have greater af"nity for D2 receptor than atypical antipsychotics Ž  risk for hyperprolactinemia, extrapyramidal symptoms, neuroleptic malignant syndrome. High-potency typical antipsychotics: haloperidol, tri!uoperazine, pimozide, !uphenazine (Hal tries pie to !y high)—more neurologic adverse effects (eg, extrapyramidal symptoms). Low-potency typical antipsychotics: chlorpromazine, thioridazine (cheating thieves are low)— more antihistaminic, anti-!1-adrenergic, antimuscarinic effects.