Anti-psychotic drugs Flashcards
What percentage of the schizophrenic population attempts suicide?
20-40%
How does PCP (phencyclidine) work?
PCP blocks the NMDA glutamate receptor and causes psychosis in many individuals
- Sometimes this psychosis never subsides
What are the typical antipsychotics (neuroleptics)?
D2 blockers (with extrapyramidal symptoms):
Chlorpromazine (Thorazine)
Perphenazine (Trilafon)
Haloperidol (Haldol)
Fluphenazine (Prolixin)
What are the effects of typical antipsychotics?
Days: calm behavior, improve sleep, decrease confusion.
Days to weeks: decrease psychotic symptoms
Weeks to months: improve insight?
In what ways are typical antipsychotics limited?
- Negative symptom improvement minimal
- Cognitive improvement usually minimal
- Disability may remain
What typical antipsychotics are low potency?
Chlorpromazine (Thorazine)
Perphenazine (Trilafon) ———–mid range
*low potency => use more mg to have an effect
What typical antipsychotics are high potency?
Haloperidol (Haldol)
Fluphenazine (Prolixin)
What are the side effects of low potency typical antipsychotics?
- Dry mouth, blurred vision, constipation, urinary retention, hypotension, sedation, weight gain
- Less acute dystonia, NMS
- Parkinsonism, akathesia, tardive dyskinesia
- Prolactin elevation (dopamine blocks prolactin secretion)
What are the side effects of high potency typical antipsychotics?
- More acute dystonia, NMS
- Parkinsonism, akathesia, tardive dyskinesia
- Prolactin elevation
What are the neurological side effects of neuroleptics (i.e. typical antipsychotics)?
- Acute dystonia
- Parkinsonism
- Akathisia
- Tardive dyskinesia (25%)
- “Rabbit” syndrome
What is neuroleptic malignant syndrome (due to neuraleptics)?
- Fever
- Rigidity
- Elevated CPK
Minor manifestations:
- tachycardia
- abnormal BP
- tachypnea
- altered consciousness
- diaphoresis
What are the benefits of atypical/novel antipsychotic drugs?
- Less EPS
- Less prolactin elevation (except risperidone, paliperidone)
- Fewer relapses
- Fewer neurological side effects
- Useful in affective psychosis (also bipolar)
- Role in suicidal patients – clozapine data
- Role in comorbid substance use –clozapine data
What are the major atypical/novel antipsychotic drugs?
- clozapine
- olanzapine
- aripiprazole
Others:
- risperidone
- quetiapine
- ziprasidone
- iloperidone
- asenapine
- lurasidone
- paliperidone
What is the action of clozapine?
Clozapine is a weak DA D2 receptor antagonist
- Potent antagonism at 5HT2 and NE α2 receptors
What are the benefits of Clozapine?
- Dramatically effective for positive and some negative symptoms.
- Minimal EPS effects.
- Minimal prolactin elevation
- Less relapse
- Can help with substance abuse remission
What side effects are associated with clozapine?
- Agranulocytosis
- Seizures
- Myocarditis
- Weight gain, glucose and lipid dysregulation
- Tachycardia, hypotension
- Drooling
- Sedation
- Liver function changes
What is the action of risperidone?
First post-clozapine atypical antipsychotic
- 5HT2/D2 ratio similar to clozapine
- alpha 2 receptor effects, strong D2 receptor blocker, some serotonin effects
*Fewer relapses than haloperidol
What are the side effects of risperidone?
EPS (higher doses), prolactin elevation
What is the action of olanzapine?
5HT/D2 receptor blockade similar to clozapine
What are the improvements in olanzapine?
Low EPS, low prolactin elevation
What are the side effects of olanzapine?
weight gain, glucose/lipid dysregulation, sedation
What is the mechanism of action of quetiapine?
5HT/D2 ratio receptor blockade similar to clozapine
What is quetiapine generally used for?
Quetiapine is a commonly used anti-psychotic for sedation
What are the improvements in quetiapine?
Few serious side effects
Minimal EPS
Minimal prolactin elevation
What is the mechanism of action of aripiprazole (abilify)?
Aripiprazole is a high-affinity D2 partial agonist
- Functional antagonist under conditions of dopamine hyperactivity =>control of positive symptoms
- Functional agonist in conditions of dopamine hypoactivity => control of negative symptoms, cognitive improvement, minimal motor effects
How is aripiprazole safer than other antipsychotics?
Minimal EPS, no prolactin elevation, low weight gain.
What side effects are associated with aripiprazole?
Early activation, insomnia
- partial agonism causes the drug to activate more than block (sometimes higher dosages are used initially)
What is the best/most effective antipsychotic?
Clozapine (but not as widely used due to side effects)
How do novel/atypical antipsychotics work?
Release of dopamine in prefrontal cortex
- alpha 2 effect on NorEpi => help to release dopamine in PFC
What is clozapine’s effect on norepinephrine?
Clozapine treatment associated with dramatic increase in plasma norepinephrine
- α2 antagonists increase efficiency of firing patterns in DA neurons in mesocorticolimbic circuits
What is the glutamatergic system?
NMDA receptors
KA receptors
AMPA receptors
Metabotropic receptors – mGluR (1 – 8)
What are other uses of antipsychotic drugs?
- Bipolar disorder, psychotic depression
- Personality disorders
- Treatment resistant depression (as adjunctive treatment)
