Pharmacology of Antipsychotics Flashcards
Describe the theories of psychosis etiology based on chemical system deficiencies
excessive DA activity in the VTA to frontal cortex pathway
excessive 5-HT2a activity
glutamate hypo function
*note all effective antipsychotic drugs reduce D2-mediated neurotransmission
Describe the class side effects of antipsychotics.
anticholinergic effects: hypertension, sedation, hyperprolactinemia, seizures, sexual dysfunction and photosensitivity
cardiac dysrhythmias:
metabolic effects: (more with atypical agents): weight gain, hyperlipidemia, insulin, insensitivity and hyperglycemia
extrapyramidal symptoms: acute dystonia, akathisia, parkinsonism, premolar tremor and tardive dyskinesia
List conditions other than schizophrenia for which antipsychotic drugs are also useful.
bipolar disorder (aripiprozole)
agitation, acute mania, bipolar disorder (Olanzapine)
Delirium and dementia with psychotic features
Disruptive behaviors associated with autism or mental retardation, acute mania
Emesis, intractable hiccups, Tourette’s syndrome, tics
Adjuncts to anxiety disorders and inhibitors for major depression
Describe the clinical presentation, course and risks of neuroleptic malignant syndrome and contrast it with serotonin syndrome.
neuroleptic malignant syndrome: onset in weeks to months of mental changes, hyperthermia, lead-pipe rigidity, tremor, autonomic instability (tachycardia, labile blood pressure, diaphoresis, agitated delirium, progressing to lethargy, stupor, coma, patient appears dazed and disoriented, incoherent speech, becomes mute
tx. with dantrolene (blocks Ca++ release in SM)
Describe the mechanism, pharmokinetics, major adverse effects and efficacy of the typical antipsychotic Chlorpromazine.
D2 receptor antagonists with strong anticholinergic and a1 blocking effects
typical antipsychotic useful for positive symptoms
metabolism by p450 enzyme, care with CNS, labor, heart disease, and Parkinson’s disease
Describe the mechanism, pharmokinetics, major adverse effects and efficacy of the typical antipsychotic Haloperidol.
D2 receptor antagonist with very weak a1 effects
50x more potent, less sedating but has more EPS symptoms, available for prompt control of agitated patients or long duration formulations
caution with CNS, Parkinson’s, (less concern with) heart disease, hepatic disease (liver metabolism)
Describe the mechanism, pharmokinetics, major adverse effects and efficacy of the atypical antipsychotic Aripiprazole.
acts as a partial agonist, at D2 and 5-HT1a, can also bind other DA and H receptors
1st line for control of positive and negative symptoms of schizophrenia
metabolized by CYP2D6 and CYP3A4, with active metabolites
adverse effects include akathisia, sedation, restlessness, tremor, NV, constipation, weight gain and hyperglycemia
What adverse effect are patients monitored for while taking Clozapine?
agranulocytosis
Describe the mechanism, pharmokinetics, major adverse effects and efficacy of the atypical antipsychotic Olanzapine.
antagonist at D1-4, 5-HT 2a (most potent) and 2c and M1-5, a1 and H1 receptors
1st line treatment: effective for positive and negative symptoms
metabolism by CYP1A2, CYP2D6
adverse effects: Drowsiness, agitation, dizziness, xerostomia, constipation, NV, transient LFT, weight gain, elevation in blood glucose, insulin sensitivity and unmasking DM
Aggrevated by anticholinergic activity, DM, Parkinson’s
Describe the mechanism, pharmokinetics, major adverse effects and efficacy of the atypical antipsychotic Quetiapine.
antagonist at D2, 5-HT, M1, a1 and H1 receptors
available PO tablets, extensively metabolized by CYP3A4
adverse effects: Xerostomia, constipation, drowsiness, agitation, dizziness, hyperlidemia, weight gain, elevation in glucose decreased, hepatic insufficiency, DM, Parkinson’s, Conditions aggravated by anticholinergic
Describe the mechanism, pharmokinetics, major adverse effects and efficacy of the atypical antipsychotic Risperidone.
antagonist at DA, 5-HT, a1, H1 receptors with antimuscarinic activity
improves both positive and negative symptoms with low anti-muscarinic activity
available PO tablets, or depot; CYP2D6 metabolism
Parkinsonims, akathisia, dizziness, drosiness, rash, weight gain, elevation in blood glucose, decreased insulin sensitivity, unmasking DM, renal insufficiency, hepatic disease, DM, Parkinson’s
