Flashcards in Antipsychotic Drugs Deck (83)
FDA approved indications for anti-psychotics
Common uses for anti-psychotics
Schizophrenia and other psychotic disorders
Major depression with psychosis
Substance induced psychosis
Which tract in the brain causes psychosis?
Mesolimbic tract (DA)
Which tract in the brain do antipsychotics work on?
Mesolimbinc tract (DA)
What are the 4 DA tracts in the brain?
Dopamine binding affinity is strongly correlated with clinical anti-psychotic effects: the higher the affinity, the ____ the dose needed for anti-psychotic effects
100 mg Chlorpromazine= __ mg Haloperidol
Haloperidol is a ___ potency drug ( ___ binding affinity)
Chlorpromazine is a ___ potency drug ( ____ binding affinity)
What are the limitations of the dopamine hypothesis?
- FGA tx of schizo was more effective against + symptoms
- 35% of treated patients relapse
-20-40% patients do not respond adequately
Other names for FGA
What are the 3 Phenothiazines (FGA) and relative potencies?
all end in "azine"
What is the 1 Thioxanthine (FGA) and relative potency?
Thiothixene - moderate
Describe the ideal therapeutic window for anti-psychotics (including tracts and % of D2 receptors bound)
Block >60-65% of D2 receptors in mesolimbic tract (anti-psychotic)
What are the effects of low potency FGAs on dopamine receptors?
Antipsychotic effect and SE
(Due to decreased dopamine and increased Ach)
What are the effects of low potency FGAs on muscarinic receptors?
blurred vision, urinary retention, dry mouth, constipation
"Can't see, can't pee, can't spit, can't shit"
"Self treating" for EPS
What are the effects of low potency FGAs on adrenergic receptors?
Orthostasis, increased fall risk
What are the effects of low potency FGAs on histamine receptors?
Sedation, weight gain
First Aid Chlorpromazine SE
First Aid Thioridazine SE
What are the 2 phenothiazines that are high potency FGA?
What is the 1 Butyrophenone high potency FGA?
High potency FGA Side Effects
Dopamine: extrapyramidal, increased prolactin (gynecomastia, galactorrhea, sexual dysfunction, menstrual irregularity/infertility), decreased bone density
No effects on muscarinic, adrenergic, or histamine receptors
What receptor(s) do high potency FGA act on?
What are some features of EPS?
Parkinsonian (resting tremor, bradykinesia, stiffness/rigidity)
What percentage of patients will develop EPS from taking high potency anti-psychotics?
What is Tardive Dyskiensia (TD), what % of patients will develop?
involuntary movements from taking DA blockers
tardive= on meds for months - years
Classically involves lower facial and tongue movements
Does not remit, even after stopping DA antagonist
Effects on which DA tract cause the extra-pyramidal side effects (EPS)?
What is acute dystonia?
Sustained abnormal posture
Occurs within a couple weeks of someone starting the meds
Made worse by activity
Patient may report as "allergic reaction"
Who is at risk for EPS-dystonia?
What is acute akathesia?
Inner sense of restlessness and need to move?
Who is at risk for acute akathesia?
Women- 2x > men
Effect on which DA tract causes the increased prolactin?
Increased prolactin causes what other symptoms?
Irregular menstruation, fertility issues
What was the first SGA developed?
List the SGA:
Describe the relative binding affinity of Clozapine for serotonin and dopamine receptors
Binding affinity for serotonin receptor is roughly 10x stronger than that for dopamine receptor
Describe the relative binding affinity for Onlazapine/Quietapine for serotonin and dopamine receptors
Both have relatively similar binding affinities for dopamine and serotonin receptors
Describe the relative binding affinity for Risperidone and ziprasidone for the serotonin and dopamine receptors
Receptor binding affinity for serotonin is higher than that for dopamine
What is the MOA of SGA?
Serotonin -Dopamine Dual Antagonism
-block post synaptic D2 receptors
-block pre synaptic 5-HT2 receptors (normally inhibit DA release> increased DA release)
Which SGA is not going to have significant anti-histaminic side effects?
Which 2 SGAs are not going to have significant anti-muscarinic (anti-cholinergic) side effects?
Risperidone and Ziprasidone
Which SGA will not have anti alpha-adrenergic side effects?
TRICK! They all have some amount of anti-alpha adrenergic SE
List in order the likelihood that SGAs will cause EPS/TD and increased prolactin
List in order the likelihood that SGAs will cause Alpha 1 related orthostasis
List in order the likelihood that SGAs will cause M1-anticholinergic SE
List in order the likelihood that SGAs will cause Histamine related sedation
List in order the likelihood that SGAs will cause metabolic syndrome (weight gain, lipids, glucose intolerance)
Which class of SGAs are worse for weight gain- the "apines" or the "idones"
What is the effect of Aripiprazole on weight?
What is the effect of Ziprasidone on weight?
Which SGA causes the most weight gain
Clozapine, followed closely by Olanzapine
SGA Partial Agonist MOA
Can have an antagonist or agonist effect depending on the level of dopamine in the env
less dopamine = agonist
more dopamine = antagonist
What are the indications for clozapine?
Pts non-responsive to other anti-psychotics
Treatment of negative symptoms of schizophrenia
Lowers the risk of suicide
What are the common SE of clozapine?
Anti- alpha adrenergic
What are the rare/serious SE of clozapine?
Decreased seizure threshold
Neuroleptic Malignant Syndrome (NMS)
Seen with SGAs or FGAs, rare
Dopamine system goes haywire
What are the symptoms of Neuroleptic Malignant Syndrome?
Mental status change
Rigidity- increased CPK, tremor
Fever >40 C
Increased HR, inc/dec BP, inc RR
Treatment of NMS (neuroleptic malignant syndrome)
Stop DA blocker
FA: dantrolene, D2 agonists-bromocriptine
Increased mortality in elderly patients with dementia psychosis
Stroke and related disorders
Increased risk with CVD
FGAs and SGAs
Recommendation for anti-psychotics in the elderly w/ dementia
Conservative use- low dose, minimize treatment length, alternative tx when available
What route of administration of the anti-psychotics provides the best bioavailability?
Anti-psychotics protein binding
90% protein bound, unbound crosses BBB
Which SGA has the longest half life?
Low potency FGA affect which receptors?
Dopamine, muscarinic, alpha-adrenergic, histamine
High potency FGA affect which receptors?
Side effects of low potency FGA correlated with receptors:
Dopamine: EPS/TD, inc prolactin
Muscarinic: treats EPS, anti-cholinergic SE
Adrenergic: dizziness, orthostasis, fall risk
Histamine: sedation, weight gain
Side effects of high potency FGA correlated with receptors:
What is the only treatment for tardive dyskinesia?
Side effects of Clozapine (SGA) correlated with receptors:
Muscarinic: v anti-cholinergic
Histamine: v sedating
Weight gain, serotonin syndrome
What is the one side effect of Lurasidone?
In Risperidone and Paliperidone, there is a dose dependent risk for ____ and ____?
EPS and increased prolactin
Which SGA carries an increased risk for increased qTC interval?
What are you options for Rx of patient with poor compliance
Long acting injectables!
What are the four long acting SGA injectables
What form is asenapine available in?
What is the side effect of Aripiprazole?
What are the two long acting FGA injectables?
Risperidone is metabolized to _______
How is palliperidone excreted?
Indications for palliperidone?
Use in pt w/ liver dises
Contraindication for palliperidone?
Renal clearance issues