Antipsychotic Drugs Flashcards
Dopamine hypothesis of schizophrenia
- Blocking D2 receptors in CNS (mesolimbic frontal system) alleviates psychotic symptoms
- Drugs that increase dopaminergic activity aggravate schizophrenia
- Schizophrenic patients have increased dopamine receptor density
Relationship between clinical efficacy of antipsychotics and affinity for D2 receptors
Higher affinity for D2 receptors = lower dose needed to achieve efficacy
EPS
Extrapyramidal symptoms- reversible neurologic effects
- Movement disorders:
- Parkinson-like syndrome
- Akathisia
- Dystonia
Akathisia
Motor restlessness- part of EPS
Dystonia
Muscle spasms- part of EPS
What do you treat acute dystonia with?
Diphenhydramine (antihistamine + anticholinergic) OR muscarinic blocking agents
Tardive dyskinesia
Choreoathetoid movements of lips/buccal cavity
-effect of chronic use of antipsychotics
Treat tardive dyskinesia
- Discontinue drug
- Eliminate drugs with anticholinergic action
- Add diazepam
Neuroleptic malignant syndrome
Most severe adverse effects of antipsychotics
- muscle rigidity, excessive sweating, autonomic instability, lead pipe rigidity, altered mental status, fever, rhabdomyelisis
- can persist for days even after neuroleptic is stopped
Treat neuroleptic malignant syndrome
Dantrolene (muscle relaxant at ryanodine receptor) + bromocriptine (dopamine agonist)
Are antipsychotics lipophilic or lipophobic?
Lipophilic- readily enter CNS
High Vd- long duration
Chlorpromazine
Typical antipsychotic- low potency
-corneal deposits
Thioridazine
Typical antipsychotic- low potency
- retinal deposits
- strongest autonomic and anti-muscarinic effects
Haloperidol
Typical antipsychotic- high potency
- blocks D2 the most –> high EPS
- weakest autonomic and muscarinic effects
Fluphenazine
High potency typical antipsychotic
Trifluoperazine
High potency typical antipsychotic
Phenothiazine
Typical antipsychotic
-sedation
What do typical antipsychotics treat?
- Positive symptoms of schizophrenia
- Motor tics
- Acute agitation/aggression
- Acute psychosis
Side effects of blocking D2 receptor in pituitary
- hyperprolactinemia
- gynecomastia
- amenorrhea
- galactorrhea
- infertility
- decreased libido
Low potency typical antipsychotics side effects
- | H1
- | a1
- | muscarinics
Mechanism of typical antipsychotics
–| D2
Can have some –| of H1, a1, muscarinics
Mechanism of atypical antipsychotics
–| 5-HT2 and a little –| D2
What do atypical antipsychotics treat?
- positive (D2) AND negative (5-HT2) symptoms of schizophrenia
- resistant MDD
Clozapine
Atypical antipsychotic (–| 5-HT2A)
- higher affinity for D4 (vs D2)
- toxicity: agranulocytosis, myocarditis/cardiomyopathy, lowered seizure threshold
- highest risk of antimuscarinic effects among atypicals
Olanzapine
Atypical antipsychotic
-metabolic toxicity
Quetiapine
Atypical antipsychotic
-QT interval prolongation
Risperidone
Atypical antipsychotic
- highest risk of causing EPS among atypicals (most D2 inhibition)
- can help manage Tourette’s
- adjunct therapy (with SSRIs) for OCD
Ziprasidone
Atypical antipsychotic
- QT interval prolongation
- lowest risk of metabolic side effect
Aripiprazole
Atypical antipsychotic
-partial agonist at D2- works by diminishing subcortical DA hyperfunction (reduces Emax) but increases DA transmission in PFC by acting as agonist
Side effects of atypical antipsychotics
- metabolic effects: weight gain, hyperlipidemia, hyperglycemia (black box warning for hyperglycemia)
- sedation (H1)
- orthostatic hypotension (a1)
- antimuscarinics (mostly just clozapine)
- prolactinemia (D2 blockade)- less so than typicals
- NMS (less so than typicals)
