99b - Antipsychotics Flashcards
What is the mechanism of action of 1st generation antipsychotics?
Blockade of the mesolimbic D2 dopamine receptors
-
High-potency agents (Haloperidol, Trifluoperazine, Fluphenazine) bind more tightly to D2 dopamine receptors
- More extrapyramidal side effects
-
Low potency agents (Thioridazine, 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
- Aripiprazile
- Lurasidone
Which antipsychotic has the greatest efficacy against the postiive 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
What are the key differences between 1st generation and 2nd generation anti-psychotics?
- 1st generation (FGA)
- Only treat positive symptoms of schizophrenia
- 2nd generation (SGA)
- Treat positive and negative symptoms of schizophrenia
- More likely to have metabolic side effects
Both low-potency FGAs and all SGAs may cause sedation, orthostatic hypotension, antimuscarinic, neuroleptic malignant syndrome
What are the symptoms of neuroleptic malignant syndrome?
Which antipsychotics are most likely to have this side effect?
- Lead pipe rigidity
- Autonomic: sweating, tachycardia
- Mental status change
- Rhabdomyolysis
Most likely in high-potency FGAs (haloperidol, trifluoperazine, 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 relevant 2nd generation (atypical) antipsychotics)
- Quetiapine
- Ziprasidone
- Olanzapine
- Risperidone (whisperidone)
- Aripiprazole
- Lurasidone
- Clozapine
Quiet! Zip it! Onlyw(r)hispers area(r)propriate in thisLittleclozet!
Low-potency, first generation antipsychotics are most likely to cause which side effects?
Low potency FGAs = Thioridazine, Chlorpromazine
- 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 the target of antipsychotic medications?
Mesolimbic dopamine system
Involved in emotions, motivation, and goal-oriented behavior
- Blocking the nigrostriatal tract results in the extrapyramidal side effects of antipsychotic medications
- Acute dystonia
- Parkinsonism
- Tardive Dyskinesia with long-term use
List the relevant 1st generation (typical) antipsychotics
- Haloperidol*
- Trifluoperazine*
- Fluphenazine*
- Thioridazine
- Chlorpromazine
* = high 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, trifluoperazine, 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)
What are extrapyramidal effects?
Which agents are most likely to cause these effects?
Extrapyramidal effects are movement-related side effects of dopamine blockade
Most likely caused by high-potency FGAs (Haloperidol, Trifluoperazine, 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 2A receptors
-> Treat + and - symptoms of schizophrenia with fewer movement-related side effects
