Antipsychotic Drugs Flashcards
42 yo pt treated with antipsychotic medication to manage schizo. Which agent is associated with skeletal muscle rigidity, tremor at rest, flat facies, uncontrollable restlessness, and spastic toritcollis? A. Haloperidol B. Clozapine C. Olanzapine D. Chlorpromazine E. Ziprasidone F. Quetiapine
A. Haloperidol
36 yo F schizo for several years. Currently on fluphenazine and experiencing amenorrhea and galactorrhea. Which agent would be more appropriate with lowest risk of current adverse effects? Which second gen agent would not be appropriate and would have near-equal risk of current effects? A. Aripiprazole B. Haloperidol C. Chlorpromazine D. Risperidone E. paliperidone
A. Aripiprazole
D. Risperidone
35 yo homeless M taking chlorpromazine for many years to control his schizo. Experiencing blurred vision, dry mouth, mydriasis, nausea, urinary retention, and constipation. Effects caused by blockade of which receptor? A. alpha adrenergic B. Dopamine C. Nicotinic D. Serotonin E. muscarinic
E. muscarinic
Pt with history of schizo is transported to emergency department by ambulance after repeated episodes of fainting. May be attributed to severe drug-induced orthostatic hypotension associated with one of her meds and thought to be due to alpha adrenergic blockade. WHat med would be most likely cause? A. Risperidone B. Thioridazine C. Aripiprazole D. Haloperidol E. Ziprasidone F. Fluphenazine
B. Thioridazine
22 yo M student BMI 49 diagnosed with schizo. Which second gen agent would be most appropriate as first line therapy and have lowest impact on BMI? A. Quetiapine B. Olanzapine C. Clozapine D. Chlorpromazine E. Ziprasidone F. Risperidone
E. Ziprasidone
Name the first generation (conventional, typical) antipsychotic agents
Chlorpromazine Fluphenazine Haloperidol Thioridazine Thiothiexene
Name the second generation (novel, atypical) antipsychotic agents
Aripiprazole Clozapine Olanzapine Quetiapine Risperidone Ziprasidone
What are the indications for antipsychotics?
Mental health conditions associated with psychosis (schizophrenia, schizoaffective disorder)
Major depressive disorder (unipolar)
Bipolar I disorder; mania or mixed
Bipolar II disorder; depression
Tourette’s disorder
Irritability with autism spectrum disorders
Recurrent suicidal behavior (clozapine)
Describe the dopamine hypothesis
Direct/indirect DA-agonists (methamphetamine and cocaine) provoke psychotic reactions in non-schizophrenics and exacerbate symptoms in schizophrenics
Alterations in DA-mediated transmission in schizophrenics (increased DA occupancy of D2 receptor)
Describe the mesolimbic pathway and positive symptoms of schizophrenia
Anatomy: projections from VTA to nucleus accumbens
Phys: motivation, emotions, reward, positive symptoms
Implications: D2 antagonists reduce positive symptoms
Positive symptoms: halluncinations, delusions, disorganized speech/thinking, agitation, abnormal motor behavior
Describe mesocortical pathway: negative and cognitive symptoms
Anatomy: projections from VTA to cortex (PFC)
Phys: cognition and executive functions (DLPFC), emotions, and affect (VMPFC)
Implications: hypofunction of mesocortical pathway might be related to cognitive and negative symptoms
Negative symptoms: apathy, abolition, alogia, cognitive deficits (working memory), social withdrawal
Describe nigrostriatal pathway and EPS
Anatomy: projections from substantia nigra (pars compacta) to striatum (caudate and putamen)
Phys: stimulation of purposeful movement
Implications: D2 antagonism induces extrapyradimal symptoms (pseudoparkinsonism)
Describe the tuberoinfundibular pathway and prolactin release
Anatomy: hypothalamus (arcuate and periventricular nuclei) to infundibular region (median eminence)
Phys: DA is released into portal circulation connecting median eminence with anterior pituitary gland. DA tonically inhibits prolactin release.
Implications: D2 antagonism increases prolactin levels
Describe the MOA of first gen antipsychotics
FGAs primarily block dopamine type2 (D2) postsynaptic receptors (D2»5HT2)
Also block one or more other receptors (primarily inducing SEs)
Muscarinic receptors
Histamine receptors (H1)
Alpha-adrenergic receptors (a1)
D2 receptors in nigrostriatal (movements) and tuberoinfundibular (prolactin) pathways
Describe the muscarinic, alpha-adrenergic, histamine, and other effects of FGA’s
Muscarinic (anti-cholinergic): dry mouth, constipation, urinary retention, blurred vision, sedation
Alpha-adrenergic: orthostatic hypotension, dizziness/syncope
Histamine: sedation
Other: risk of QTc prolongation and seizure activity
Describe the dopamine effects of FGAs
Hyperprolactinemia (tuberoinfundibular pathway): amenorrhea/galactorrhea/gynecomastia/decreased libido
Extrapyramidal symptoms (EPS)/Tardive dyskineisia (TD) (nigrostriatal pathway)
Acute dystonia/akathisia/dyskinesia/Parkinsonism-like
**Treatments
-anticholinergic agents: diphenhydramine, benztropine, trihexyphenidyl
-non-anticholinergic: amantadine (antiviral)
-propranolol/clonazepam for akathisia
Describe low potency vs high potency agents based on D2 potency/receptor occupancy of FGAs
Low potency:
More sedation, hypotension, and seizure-threshold reduction
Agents: chlorpromazine, thioridazine
High potency: More movement (EPS) and endocrine effects (prolactin) Agents: fluphenazine, haloperidol, thiothixene
What are limits to dopamine hypothesis?
Does not account for all cognitive deficits/negative symptoms associated with schizophrenia (related to decreased DA signaling in prefrontal cortex)
Does not fully explain role of 5HT2 (LSD, 5HT agonist)
Does not fully explain role of NMDA/glutamate (PCP/ketamine, antagonist)
Describe MOA of second generation antipsychotics (SGAs)
Block dopamine type2 (D2) postsynaptic receptors and 5HT2A
Stronger 5HT2a blocker»_space; D2
Describe the SGA dual 5HT2a/D2 theory
5HT2a antagonism increases DA transmission in nigrostriatal pathway
May contribute to improved negative and cognitive symptoms via increased DA release in PFC
Reduced EP SE’s
SGAs may rapidly dissociate more from D2 receptors (reduced EP SE’s)
Some SGAs are D2 partial agonists (aripiprazole)
Some SGAs are 5HT1A full agonist (ziprasidone) or partial agonists (aripiprazole and clozapine)
Some also block one or more other DA receptor and have greater propensity to be agonist/antagonist on one or more other 5HT receptors
Describe side effects of SGAs
Common:
Weight gain
Metabolic effects (hyperglycemia/insulin resistance, hyperlipidemia)
Rare: QTc prolongation/ECG changes: negative inotropic actions (greater risk for women, elderly, and those on antiarrhtymics) Stroke: greater risk in elderly with dementia (increase all-cause mortality with all antipsychotics (class warning))
Which FGAs and SGAs have the most and least risk for weight gain and diabetes?
SGAs higher risk > FGAs
FGA:
Most: chlorpromazine (most), thioridazine, thiothixene
Least: fluphenazine, haloperidol
SGA:
Most: Olanzapine
Least: Aripiprazole, ziprasidone
Which FGAs and SGAs have the most and least risk for hypercholesterolemia?
SGAs higher risk > FGAs
FGAs:
Most: chlorpromazine
Least: fluphenazine, haloperidol
SGAs:
Most: Olanzapine (most), quetiapine
Least: aripiprazole, ziprasidone
Which FGAs and SGAs have the most and least risk for EPS/tardive dyskinesia?
FGAs higher risk > SGAs
FGAs:
Most: fluphenazine, haloperidol, thiothixene
Least: chlorpromazine, thioridazine
