Antipsychotics - SGA's Flashcards
Name the SGA’s
Clozapine
Risperidone Ziprasidone Iloperidone Paliperidone Lurasidone
Olanzapine
Asenzapine
Quetiapine
Aripiprazole
Which SGA is the first “atypical” antipsychotic and what was special about it?
Clozapine
It didn’t given EPS/Tardive Dyskinesia
What’s unique about Aripiprazole?
Partial Agonist MOA
Describe receptor binding for clozapine.
Receptor binding of 5HT2 is 10x stronger than DA blocking
Describe receptor binding for olanzapine and quetiapine
Similar binding affinities for 5HT2 and D2
Describe receptor binding for risperidone and ziprasidone
There’s greater 5HT2C antagonism
What is the 5HT-DA antagonism hypothesis?
Blocking presynaptic 5-HT2A gives inc DA release in basal ganglia (nigrostriatal system)
The DA competes with the antipsychotic medication for D2 receptors
Simultaneous antagonism of DA and 5-HT2 results in a net dec of the degree to which D2 receptors are blocked in the striatum - leads to dec EPS/tardive dyskinesia
*most clearly noticed at low doses
What is the hit and run hypothesis?
Minority view
DA blockade is “loose” and doesn’t last long enough to give DA side effects (but lasts long enough to give antipsychotic effect)
What 2 medications does the Hit and Run hypothesis apply to?
Clozapine and Quetiapine
Which SGA doesn’t have significant anti-histaminic effects?
Risperidone
Which SGAs don’t have anti-muscarinic/anti-cholinergic side effects?
Risperidone and Ziprasidone
Which SGA doesn’t really have Metabolic syndrome side effects?
Ziprasidone
Which SGAs don’t really have EPS and hyperprolactinemia?
Quetiapine and Clozapine
*Thus it supports the hit and run hypothesis
What symptoms are seen in metabolic syndrome?
Weight gain, hyperglycemia, diabetes mellitus, dyslipidemia
With metabolic syndrome, there is an increased rate of what disease?
Cardiovascular Disease
What are the top 2 SGAs that give weight gain?
Clozapine and Olanzapine
What SGA’s don’t really have weight gain as an issue?
Ziprasidone, Aripiprazole, Lurasidone, Asenapine
Which SGA is a partial agonist?
Aripiprazole
What is the Rheostat analogy?
Says that the receptor is neither completely on or off - the drug is changeable depending on amount of receptor stimulation
According to the rheostat analogy, in a low neuroreceptor stimulation environment, what happens
With the partial agonist there’s little AGONIST
activity (the cell isn’t completely OFF)
According to the rheostat analogy, in a high neuroreceptor stimulation environment, what happens
With the partial agonist there’s little ANTAGONIST activity (the cell isn’t completely ON)
What does Aripiprazole do in low DA environments?
Binds to D2 receptors with high affinity and acts as agonist
Keeps
What does Aripiprazole do in high DA environments?
Binds/blocks D2 recetors and acts as antagonist
Keeps >65% but
What is the first DA-5HT system stabilizer?
Aripiprazole
When is Clozapine used?
3rd line treatment used after failure of at least 2 other antipsychotics
Which medication is high risk and high reward? What does this mean?
Clozapine
How is Clozapine high reward?
High reward - More effective than any other medications in treatment resistant patients as well as reducing suicide risk, also helps with negative symptoms (may even with treating tardive dyskinesia )
How is Clozapine high risk?
High risk - serious side effects associated with it
What are common side effects of Clozapine?
Sedation
Weight gain
Metabolic syndrome
Anti-chilinergic
What are rare/serious side effects of Clozapine?
AGRANULOCYTOSIS - bone marrow stops producing wbcs
Myocarditis
Dec seizure threshold (aka inc seizure risk)
Asenapine has an increased risk of?
EPS
QTc elongation is seen with which meds?
Thioridazine (FGA) > Ziprasdisone (SGA) > others
Top 2 for sedation are?
Clozapine and Olanzapine
NMS (Neuroleptic Malignant Sydrome) is a rare side effect of what drugs?
FGAs
SGAs
MEtoclopramide
Prochlorperazine
What happens with NMS (Neuroleptic Malignant Sydrome)?
DA system goes haywire Mental status changes/confusion Rigidity (tremor and inc CPK) Fever > 40 degrees Celsius Dysautonomia (inc HR, BP change, inc RR, hypoxia)
Is inc CPK diagnostic for NMS?
Not by itself
It helps gauage how severe the NMS is
How long does it take for NMS to resolve?
7-10 days
How do you treat NMS?
Stop the medication!
Supportive therapy
What is a black box warning for SGAs and FGAs?
Risk of inc mortality (sudden death) in elderly who have dementia with psychosis
Typically from CV or stroke
How do you alter SGA/FGA use in elderly?
Low dose (risk inc with higher doses)
Minimize treathment length
Use something else if possible
What population may be at an inc risk of sudden death with FGAs/SGAs?
Elderly
ex: nursing homes
Describe PK (bioavailability) of FGAs/SGAs
IM > PO
PO gives incomplete absorption and first pass effect
Peak plasma level for FGAs/SGAs in IM vs PO
IM = 30 min PO = 1-4 hrs
Protein binding of FGAs/SGAs?
90% protein bound
Unbound passes thru BBB
*is very lipid soluble
FGAs/SGAs are stored where?
In body fat
Half life of FGAs/SGAs? Steady state?
Half life of 20 hours
Steady state 4-7 days
What’s the exception to half lives for SGAs and what is it’s half life?
Aripiprazole
Has a long half life of about 3 days
Clozapine is used for?
Refractory schizo
EPS side effects and inc prolactin is dose dependent for?
Risperidone and Paliperidone
Inc qTc interval is a concern with?
Ziprasidone
Akathisia is a concern with?
Lurasidone (and Aripiprazole)
Which drug is only available as a sublingual form?
Asenapine
Long acting injectable form is seen with?
Aripiprazole
Risperidone/Paliperidone
Haldol (FGA)
Flufenazine (FGA)
Risperidone is metabolized to?
Palliperidone
Palliperidone is used for?
Liver disease b/c 80% renal excretion
Ziprasidone and Lurasidone are taken with ___?
Food b/c 50% better absorption
If less than 80% nigrostriatal D2 receptors are blocked, then?
Reduced/No EPS
If less than 80% tuberoinfundibular D2 receptors are blocked, then?
Decreased/No hyperprolactinemia
