115: Antipsychotics Flashcards
What is the mechanism of action of 1st generation antipsychotics?
Blockade of the mesolimbic D2 dopamine receptors
-
High-potency agents (Haloperidol, Fluphenazine) bind more tightly to D2 dopamine receptors
- More extrapyramidal side effects
- Medium Potency: Perphenazine, trifluoperazine
-
Low potency agents (Chlorpromazine) bind less tightly to D2 dopamine receptors
- Fewer extrapyramidal side effects
- More side effects due to anticholinergic, antihistamine effect
Which atypical antipsychotics cause the least disturbance in metabolic profile?
- Ziprazidone
- Aripiprazole
- Lurasidone
Which antipsychotic has the greatest efficacy against the postive symptoms of schizophrenia?
What are the associated (potentially fatal) side effects specific to this agent?
Clozapine (Atypical/2nd generation)
May cause potentially fatal neutropenia and agranulocytosis
As a result, used as a 3rd line agent despite efficacy; patients must register in database to document neutropenic reaction/prevent prescription in the future
What is the difference between efficacy and potency?
- Efficacy = ability to achieve the desired clinical effect
- Potency = how much medication is needed
- Higher potency = lower systemic levels needed for effect
- Efficacy is aligned with the affinity for the MESOLIMBIC D2 RECEPTS
What are the key differences between 1st generation and 2nd generation anti-psychotics?
- 1st generation (FGA)
- Only treat positive symptoms of schizophrenia
- Dopamine blockade
- 2nd generation (SGA)
- Treat positive and negative symptoms of schizophrenia
- More likely to have metabolic side effects
- Dopamine AND serotonin blockade (higher affinity for serotonin)
Both low-potency FGAs and all SGAs may causesedation, orthostatic hypotension, antimuscarinic, neuroleptic malignant sydrome
What are the symptoms of neuroleptic malignant syndrome?
Which antipsychotics are most likely to have this side effect?
- Fever
- Autonomic instability
- Delirium
- Rigid muscle tone
Most likely when starting high-potency first gen meds (haloperidol, fluphenazine)
Which dopamine system is involved in producing the extra-pyramidal side effects associated with 1st generation antipsychotics?
What are these side effects?
Nigrostriatal tract
Involved in fine control of movement
- Acute dystonia
- Parkinsonism
- Tardive Dyskinesia with long-term use
List the 7 relevant 2nd generation (atypical) antipsychotics)
- Quetiapine
- Ziprasidone
- Olanzapine
- Risperidone (whisperidone)
- Aripiprazole
- Lurasidone
- Clozapine
Quiet! Zip it! Only w(r)hispers are a(r)propriate in this Little clozet!
Low-potency, first generation antipsychotics are most likely to cause which side effects?
Low potency FGAs =Chlorpromazine
All the HAM side effects
- Sedation
- Due to histamine blockade (may be useful in the hospital)
- Dry mouth, urinary retention, constipation, blurred vision
- Due to muscarinic blockade
- Orthostatic hypotension
- Due to alpha-1 blockade
- Neuroleptic malignant syndrome
- But less likely than 1st generation
Note: extrapyramidal, hypergallactorea, tardive dyskinesia much less likely
Which dopamine systems are effected by antipsychotic medications?
Anti-psychotics have clinical efficacy from blockade of D2 receptors in the mesolimbic pathway, but may also hit
- Mesolimibic→ clinical effects of anti-psychotic
- Nigrostriatal→ extra pyramidal side effects
- Mesocortical→ may worsen negative systems of schizophrenia
- Tuveroinfundibular→ hyperprolactinemia
List the 5 relevant 1st generation (typical) antipsychotics
- Haloperidol (HIGH)
- Fluphenazine (HIGH)
- Trifluoperazine (MEDIUM)
- Perphenazine (MEDIUM)
- Chlorpromazine (LOW, first drug developed)
(POTENCY)
Hal tried to fly but Thor Clorbbered him
Thor and Hal are old (like Van Gogh in the sketchy), so these are 1st gen
(The r in thor matches chlorpromazine; don’t get confused with clozapine, a 2nd gen)
High-potency, first generation antipsychotics are most likely to cause which side effects?
High potency FGA = haloperidol, fluphenazine
- Extrapyramidal symptoms
- Parkinsonism
- Dystonia
- Tardive dskenesia after years of use
- Hyperprolactinemia
- Higher risk of neuroleptic malignant syndrome
What are the indications for antipsychotic medications?
Schizophenia is the most common use
Other uses include
- 1st generation
- Acute psychotic episodes in many conditions
- Acute agitation and aggression (especially haloperidol)
- 2nd generation
- Treatment-resistant depression
- OCD ad-junct (with SSRIs)
- Honestly being used off-label for a ton of stuff
What are extrapyramidal effects?
Which agents are most likely to cause these effects?
Extrapyramidal effects are movement-related side effects of dopamine blockade (from nigrostriatal pathway)
Most likely caused by high-potency FGAs (Haloperidol, Fluphenazine)
- Dystonic reactions (acute, painful, involuntary muscle spasm)
- Drug-induced parkinsonism
- Akathisia (restlessness, anxiety)
- Tardive Dyskinesia
- Occurs after long term use
What is the mechanism of the 2nd generation (atypical) antipsychotics?
Block D2 receptors in the CNS
Block 5-HT (serotonin) 2A receptors
-> Treat + and - symptoms of schizophrenia with fewer movement-related side effects
