Antipsychotics MOA Flashcards
D2 antagaonization adverse effects
Mesolimbic: Reduction of positive sx
Mesocortical: worsen/cause negative sx
Tuberofundibular: hyperprolactinemia
Nigrastriatal: worsening of movement disorders (EPS early, TD late effect)
Clinical effects of D2 antagonism
Reduce positive sx of schizophrenia
Histamine (H1) antagonism
Sedation, apprtite stimulation, weight gain
Muscarinic (M1) antagonism
Anticholinergic effects
Noradrenergic (alpha-1)
Orthostatic hypotension
Serotonin (5-HT2A)
May increase DA activity in mesocortical pathway (improving -ve sx) and nigrostriatal (decreasing EPS)
Lab tests for Antipsychotics general
ECG at baseline EEG if seizures of myoclonus occur Fasting blood glucose at baseline and routinely (6mo,12mo then annually) A1c if impaired fbg ot diabetes present Lipid at baseline and routinely as indicated CBC baseline and as indicated LFT baseline then 1mo then as indicated Prolactin level as indicated
What are 2nd gen AP?
Olanzapine Quetiapine Risperidone Paliperidone Ziprasidone Lurasidone Asenapine Clozapine
What are 3rd gen AP
Brexpiprazole
Aripiprazole
What are 1st gen AP
Low: Chlorpromazine, methotrimeprazine
Inter: loxapine, perphenazine, zuclopenthixol
High: flupentixol, fluphenazine, haloperidol, pimozide, trifluoperazine
What determines potency?
D2 receptor binding affinity
Low vs high potency AE
Low potency cause more alpha-1, H1, and M1 AE (postural hypotension, sedation, anticholinergic)
High potency cause more D2 related AE (EPS, hyperprolactinemia)
Moderate potency fall in between
FGA general Adverse Effects
CNS: confusion, disturbed concentration, disorientation (high dose/elderly), EPS, TD, NMS, sedation, seizures (lower threshold)
Anticholinergic: blurry vision, dry eyes, constipation, delirium, dry mouth, urinary retention
CV: arrhythmias, QTc, tachycardia, ortho hypotension, syncope, VTE,
Endocrine: dyslipidemia, antidiuertic hormone dysfunction (polydipsia, hyponatremia), glucose intolerance, hyperprolactinemia, metabolic syndrome, weight gain
GI: sialorrhea, dyspepsia
Sexual: decreased libido, anorgasmia, ejaculatory/erectile dysfunction,
Heme: blood dyscrasias (aplastic anemia, eosinophilia, leukopenia, thrombocytopenia)
Temperature dysregulation
FGA discontinuation syndrome
Exacerbation of psychosis, movement disorders, rebound type reaction when prolonged antagonist is removed, other typical D/C symptoms (N/V, diaphoresis, insomnia, anxiety, confusion, muscle pain etc.)
DI with alpha-1 blockers (prazosin, doxazosin etc.) effect
Additive hypotension, esp with low potency
DI with adsorbants (cholestyramine, charcoal, attapulgite) effects
Oral absorption decreased when used simultaneously; give 1h before or 2h after AP