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MRPsych > Antipsychotics - SGA's > Flashcards

Antipsychotics - SGA's Flashcards

1
Q

Name the SGA’s

A

Clozapine

Risperidone
Ziprasidone
Iloperidone
Paliperidone
Lurasidone

Olanzapine
Asenzapine
Quetiapine

Aripiprazole

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2
Q

Which SGA is the first “atypical” antipsychotic and what was special about it?

A

Clozapine

It didn’t given EPS/Tardive Dyskinesia

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3
Q

What’s unique about Aripiprazole?

A

Partial Agonist MOA

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4
Q

Describe receptor binding for clozapine.

A

Receptor binding of 5HT2 is 10x stronger than DA blocking

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5
Q

Describe receptor binding for olanzapine and quetiapine

A

Similar binding affinities for 5HT2 and D2

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6
Q

Describe receptor binding for risperidone and ziprasidone

A

There’s greater 5HT2C antagonism

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7
Q

What is the 5HT-DA antagonism hypothesis?

A

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

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8
Q

What is the hit and run hypothesis?

A

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)

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9
Q

What 2 medications does the Hit and Run hypothesis apply to?

A

Clozapine and Quetiapine

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10
Q

Which SGA doesn’t have significant anti-histaminic effects?

A

Risperidone

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11
Q

Which SGAs don’t have anti-muscarinic/anti-cholinergic side effects?

A

Risperidone and Ziprasidone

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12
Q

Which SGA doesn’t really have Metabolic syndrome side effects?

A

Ziprasidone

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13
Q

Which SGAs don’t really have EPS and hyperprolactinemia?

A

Quetiapine and Clozapine

*Thus it supports the hit and run hypothesis

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14
Q

What symptoms are seen in metabolic syndrome?

A

Weight gain, hyperglycemia, diabetes mellitus, dyslipidemia

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15
Q

With metabolic syndrome, there is an increased rate of what disease?

A

Cardiovascular Disease

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16
Q

What are the top 2 SGAs that give weight gain?

A

Clozapine and Olanzapine

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17
Q

What SGA’s don’t really have weight gain as an issue?

A

Ziprasidone, Aripiprazole, Lurasidone, Asenapine

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18
Q

Which SGA is a partial agonist?

A

Aripiprazole

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19
Q

What is the Rheostat analogy?

A

Says that the receptor is neither completely on or off - the drug is changeable depending on amount of receptor stimulation

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20
Q

According to the rheostat analogy, in a low neuroreceptor stimulation environment, what happens

A

With the partial agonist there’s little AGONIST

activity (the cell isn’t completely OFF)

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21
Q

According to the rheostat analogy, in a high neuroreceptor stimulation environment, what happens

A

With the partial agonist there’s little ANTAGONIST activity (the cell isn’t completely ON)

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22
Q

What does Aripiprazole do in low DA environments?

A

Binds to D2 receptors with high affinity and acts as agonist

Keeps

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23
Q

What does Aripiprazole do in high DA environments?

A

Binds/blocks D2 recetors and acts as antagonist

Keeps >65% but

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24
Q

What is the first DA-5HT system stabilizer?

A

Aripiprazole

25
Q

When is Clozapine used?

A

3rd line treatment used after failure of at least 2 other antipsychotics

26
Q

Which medication is high risk and high reward? What does this mean?

A

Clozapine

27
Q

How is Clozapine high reward?

A

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 )

28
Q

How is Clozapine high risk?

A

High risk - serious side effects associated with it

29
Q

What are common side effects of Clozapine?

A

Sedation
Weight gain
Metabolic syndrome
Anti-chilinergic

30
Q

What are rare/serious side effects of Clozapine?

A

AGRANULOCYTOSIS - bone marrow stops producing wbcs
Myocarditis
Dec seizure threshold (aka inc seizure risk)

31
Q

Asenapine has an increased risk of?

A

EPS

32
Q

QTc elongation is seen with which meds?

A

Thioridazine (FGA) > Ziprasdisone (SGA) > others

33
Q

Top 2 for sedation are?

A

Clozapine and Olanzapine

34
Q

NMS (Neuroleptic Malignant Sydrome) is a rare side effect of what drugs?

A

FGAs
SGAs
MEtoclopramide
Prochlorperazine

35
Q

What happens with NMS (Neuroleptic Malignant Sydrome)?

A 
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)
36
Q

Is inc CPK diagnostic for NMS?

A

Not by itself

It helps gauage how severe the NMS is

37
Q

How long does it take for NMS to resolve?

A

7-10 days

38
Q

How do you treat NMS?

A

Stop the medication!

Supportive therapy

39
Q

What is a black box warning for SGAs and FGAs?

A

Risk of inc mortality (sudden death) in elderly who have dementia with psychosis

Typically from CV or stroke

40
Q

How do you alter SGA/FGA use in elderly?

A

Low dose (risk inc with higher doses)
Minimize treathment length
Use something else if possible

41
Q

What population may be at an inc risk of sudden death with FGAs/SGAs?

A

Elderly

ex: nursing homes

42
Q

Describe PK (bioavailability) of FGAs/SGAs

A

IM > PO

PO gives incomplete absorption and first pass effect

43
Q

Peak plasma level for FGAs/SGAs in IM vs PO

A 
IM = 30 min
PO = 1-4 hrs
44
Q

Protein binding of FGAs/SGAs?

A

90% protein bound
Unbound passes thru BBB
*is very lipid soluble

45
Q

FGAs/SGAs are stored where?

A

In body fat

46
Q

Half life of FGAs/SGAs? Steady state?

A

Half life of 20 hours

Steady state 4-7 days

47
Q

What’s the exception to half lives for SGAs and what is it’s half life?

A

Aripiprazole

Has a long half life of about 3 days

48
Q

Clozapine is used for?

A

Refractory schizo

49
Q

EPS side effects and inc prolactin is dose dependent for?

A

Risperidone and Paliperidone

50
Q

Inc qTc interval is a concern with?

A

Ziprasidone

51
Q

Akathisia is a concern with?

A

Lurasidone (and Aripiprazole)

52
Q

Which drug is only available as a sublingual form?

A

Asenapine

53
Q

Long acting injectable form is seen with?

A

Aripiprazole
Risperidone/Paliperidone
Haldol (FGA)
Flufenazine (FGA)

54
Q

Risperidone is metabolized to?

A

Palliperidone

55
Q

Palliperidone is used for?

A

Liver disease b/c 80% renal excretion

56
Q

Ziprasidone and Lurasidone are taken with ___?

A

Food b/c 50% better absorption

57
Q

If less than 80% nigrostriatal D2 receptors are blocked, then?

A

Reduced/No EPS

58
Q

If less than 80% tuberoinfundibular D2 receptors are blocked, then?

A

Decreased/No hyperprolactinemia

MRPsych (20 decks)

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