Atypical & Typical Antipsychotics Flashcards

Question 1

Q

Identify major First Generation/Typicals (FGA) drugs

Question 2

Q

Apply the pharmacological concepts underlying the use of FGAs

Question 3

Q

Describe the mechanism of action of how the various FGAs work

Question 4

Q

Examine how FGAs act upon, amplify, and modify neural functions, ultimately affecting mood and behavior

Question 5

Q

Analyze the use of FGAs in clinical practice, including combination or augmentation strategies.

Question 6

Q

Understand the art of psychopharmacology including potential advantages, disadvantages and primary target symptoms of various FGAs.

Question 7

Q

Discuss precautions, contraindications, and implications of FGAs use in special populations including those with hepatic, renal or cardiac impairment, elderly, children and adolescents, pregnancy and lactation.

Question 8

Q

Identify major Second Generation/Atypicals (SGA) drugs.

Question 9

Q

Apply the pharmacological concepts underlying the use of SGAs

Question 10

Q

Describe the mechanism of action of how the various SGAs work.

Question 11

Q

Examine how SGAs act upon, amplify, and modify neural functions, ultimately affecting mood and behavior.

Question 12

Q

Analyze the use of SGAs in clinical practice, including combination or augmentation strategies.

Question 13

Q

Understand the art of psychopharmacology including potential advantages, disadvantages and primary target symptoms of various SGAs.

Question 14

Q

Meaning of Neuroleptic/ Conventional Antipsychotics/ Typical antipsychotics

Answer

A

The term used for 1st generation antipsychotics because of their ability to produce neurolepsis

Question 15

Q

Meaning of Neurolepsis

Answer

A

Psychomotor slowing, Emotional quieting, Affective indifference

Question 16

Q

Meaning of Atypical antipsychotic/ second-generation antipsychotics

Answer

A

Lower risk extrapyramidal symptoms, Efficacy against cognitive and negative symptoms, Lack of prolactin elevation, Efficacy for treatment-resistant patients

Question 17

Q

Atypical Antipsychotics/ Second Generation antipsychotics

Answer

A

Serotonin-dopamine antaganist

Question 18

Q

Third generation antipsychotics

Answer

A

Dopamine partial agonist (Aripiprazole is the only FDA approved)

Question 19

Q

First Generation Antipsychotics (FGAs) adverse effects

Answer

A

Higher risk of Neurological side effects

Question 20

Q

Second Generation Antipsychotics (SGAs) adverse effects

Answer

A

Lower risk of neurological side effects

Higher risk of metabolic side effects - Weight gain, DM, obesity,

Question 21

Q

First Generation Antipsychotics notes

Answer

A

Are D2 antagonists (remember D2R = detour from reality)

Are associated with higher risk of extrapyramidal sx (EPS)

Question 22

Q

Second Generational Antipsychotics notes

Answer

A

Are 5HT2A/D2 antagonsits

Lower risk EPS

Higher risk of Metabolic sx

Question 23

Q

DOPAMINE Mnemonic related to FGAs blocked

Answer

A

Drive - “slow but not sleepy”, clumsy
psychOsis - hallucinations and delusions
Parkinsonism - PArkinson’s Disease = doPAmine Down
Attention - “difficult for me to explain”, want to finish as soon as possible
Motor -
Inhibition of prolactin
Narcotics
Extrapyramidal - involuntary motor tracks,

Question 24

Q

Extrapyramidal Side Effects

Answer

A

Acute Dystonia - “muscle” contraction - 4 hours

Akathisia - “Rustle” restlessness, jittery - 4 Days

Akinesia - “Hustle” shuffle/inability to move - 4 Weeks

Tardive Dyskinisa

Hyperprolactinemia - increased breast size - RISE-PAIRidone gives RISE to a PAIR

Neuroleptic Malignant Syndrome - Confusion, Agitation, Hyperthermia (>105 F), Muscular Ridgity, Seizures + Recent Antipsychotic use = NMS!

Question 25

Q

Tardive Dyskinesia

Answer

A

Extrapyramidal side effect

Can be IRREVERSIBLE

Constant involuntary periorbital muscles

CHEWING TARdive

Treated with Benadryl

Question 26

Q

Neuroleptic Malignant Syndrome Sx & Tx

Answer

A

Confusion, Agitation, Hyperthermia (>105 F), Muscular Ridgity, Seizures + Recent Antipsychotic use = NMS!

Tx w/ Dantrolene (hint DANtrolene Never Missed a Step)

Question 27

Q

dosing form note to remember

Answer

A

PO before DEPOT

PO to confirm they can tolerate the med b4 giving the med as a Depot IM injection that will be in place and affecting the pt for weeks

Question 28

Q

Chlorpromazine/ Thorazine

Answer

A

FGAs

Affects DA-, Ach-, NE-, His-

Wide Side Effect Profile
Sediment Deposits in Cornea - (hint CHLOR-neal Deposits)

Question 29

Q

Thoridazine/ Mellaril

Answer

A

FGAs

Affects DA-, ACH-

Side effect - retinal deposits (Thioridazine= reTinal deposits

Question 30

Q

Haloperidol/ Haldol

Answer

A

FGAs

Affects DA- (more D2 receptor-specific)

HOLDol

Less anticholinergic, Antihystamic, and Antinoredergic affects

Higher rate of extrapyramidal side effects

Depot formula is the Decanoate = DECAde

Question 31

Q

Clozapine/ Clozaril

Answer

A

SGAs

affects DA- & SE partial agonist

Most effective agent against schizophrenia

The deadly side effect of agranulocytosis (the loss of all WBC)

watch it CLOZely for agranulocytosis

never 1st line

Must be registered and the ANC checked prior and serial ANC throughout the 1st year

D/C immediately if ANC falls below 1500

Question 32

Q

Olanzapine/ Zyprexa

Answer

A

SGAs

DA- SE+

Second only to clozapine in efficacy but without the side effect of agranulocytosis

IS a 1st line treatment for schizophrenia

Highest of all prescribed but also the worst for weight gain without increased caloric intake

Think Olanzapine and an Obesie person

O for Obesity

Question 33

Q

Risperidone/ Risperdal

Answer

A

SGAs

DA- SE- NE- His-

RISe & Shine (less sedation)
RISe to a Pair

Low EPS sx
High Metabolic syndrome

High relation to Gynocomystomy

Question 34

Q

Quetiapine/ Seroquel

Answer

A

SGAs

DA- SE- NE- HIS-

Low EPS sx
High Metabolic syndrome

Quetiapine = Quiet time (increased sedation)

Question 35

Q

Ziprasidone/ Geodon

Answer

A

SGAs

DA- SE- NE- HIS-

Low EPS sx
High Metabolic syndrome

Prolongs QT interval

Geodon think GEOmetro a Zippy Car (reminding u to do an EKG

Question 36

Q

Aripiprazole/ Abilify

Answer

A

Third Generation As

DA partial agonist, SE partial agonist

Helps with maintenance therapy not acute psychosis

Think And Abilify for dopamine and serotonin

Antidepressant AND Abilify for refractory cases of MDD

Question 37

Q

Description of Psychosis

Answer

A

Psychosis is a syndrome, a mixture of symptoms that can be associated with many different psychiatric disorders but is not a specific disorder itself in DSM or ICD diagnostic criteria.

Question 38

Q

Symptoms of Psychosis

Answer

A

At a minimum, delusions and hallucinations and generally includes symptoms such as disorganized speech, disorganized behavior, and gross distortions of reality.

Question 39

Q

Types of Psychosis

Answer

A

Paranoid Psychosis - Paranoid Projections; Hostile Belligerence & Grandiose Expansiveness

Disorganized/Excited Psychosis - Conceptual Disorganization, Disorientation, Excitement

Depressive Psychosis - Psychomotor retardation & Apathy; Anxious Self-Punishment & Blame

Question 40

Q

Paranoid Psychosis -

Answer

A

Paranoid Projections; Hostile Belligerence & Grandiose Expansiveness

Question 41

Q

Disorganized/Excited Psychosis -

Answer

A

Conceptual Disorganization, Disorientation, Excitement

Question 42

Q

Schizophrenia consists of

Answer

A

a mixture of symptoms that are commonly divided into two major categories: Positive and Negative symptoms

Question 43

Q

Schizophrenias Positive symptoms are

Answer

A

Delusion and hallucinations, reflect the development of the symptoms of psychosis; they can be dramatic and may reflect a loss of touch with reality.

Question 44

Q

Schizophrenia Negative symptoms will

Answer

A

Reflect the loss of normal functions and feelings, such as losing interest in things and not being able to experience pleasure. Think alogia, affective blunting or flattening, asociality, anhedonia, avolition & attentional impairment.

Question 45

Q

Alogia

Answer

A

The poverty of speech, (talks little, uses few words)

Dysfunction of Communication

Neg Sx of Schizophrenia

Question 46

Q

Affective blunting

Answer

A

Reduced range of emotions (perception, experience, and expression) ex - feels numb or empty inside, recalls few emotional experiences, good or bad

Dysfunction of Affect

Neg Sx of Schizophrenia

Question 47

Q

Asociality

Answer

A

Reduced social drive and interactions ( little sexual interest, few friends, little interest in spending time with (or little time spent with) friends)

Dysfunction of socialization

Neg Sx of Schizophrenia

Question 48

Q

Anhedonia

Answer

A

Reduced ability to experience pleasure (finds previous hobbies or interests unpleasurable

Dysfunction of capacity for pleasure

Neg Sx of Schizophrenia

Question 49

Q

Avolition

Answer

A

Reduced desire, motivation, and persistence, (reduced ability to undertake and complete everyday tasks, may have poor personal hygiene)

Dysfunction of motivation

Neg Sx of Schizophrenia

Question 50

Q

Different symptom domains of schizophrenia are hypothesized to be regulated by unique brain regions:

Answer

A

Positive symptoms - mesolimbic

Negative symptoms - mesocortical/ prefrontal cortex

Cognitive sx - the dorsolateral prefrontal cortex

Aggressive sx - orbitofrontal cortex

Affective sx - the ventromedial prefrontal cortex

Question 51

Q

Five dopamine pathways in the brain

Answer

A

he mesolimbic dopamine pathway,

the mesocortical dopamine pathway,

the nigrostriatal dopamine pathway,

the tuberoinfundibular dopamine pathway, and

a fifth pathway that innervates the thalamus.

Question 52

Q

Mesolimbic dopamine pathway and positive symptoms of schizophrenia

Answer

A

The mesolimbic dopamine pathway projects from dopaminergic cell bodies in the ventral tegmental area of the brainstem to axon terminals in one of the limbic areas of the brain, namely the nucleus accumbens in the ventral striatum

This pathway is thought to have an important role in several emotional behaviors, including the positive symptoms of psychosis, motivation, pleasure, and reward.

It has long been observed that diseases or drugs that increase dopamine will enhance or produce positive psychotic symptoms, whereas drugs that decrease dopamine will decrease or stop positive symptoms. For example stimulant drugs such as amphetamine and cocaine release dopamine, and if given repetitively can cause a paranoid psychosis virtually indistinguishable from the positive symptoms of schizophrenia.

All antipsychotic drugs capable of treating positive psychotic symptoms are blockers of the dopamine D2 receptor. These observations have been formulated into a theory of psychosis sometimes referred to as the “dopamine hypothesis of schizophrenia” or “mesolimbic dopamine hypothesis of positive symptoms of schizophrenia.”

Hyperactivity of the mesolimbic dopamine pathway hypothetically accounts for positive psychotic symptoms whether those symptoms are part of the illness of schizophrenia, or of drug-induced psychosis, or whether they are positive psychotic symptoms accompanying mania, depression, or dementia.

Hyperactivity of mesolimbic dopamine neurons may also play a role in aggressive and hostile symptoms in schizophrenia and related illnesses.

Question 53

Q

Hyperactivity of the mesolimbic dopamine pathway hypothetically accounts for

Answer

A

positive psychotic symptoms whether those symptoms are part of the illness of schizophrenia, or of drug-induced psychosis, or whether they are positive psychotic symptoms accompanying mania, depression, or dementia.

Question 54

Q

Hyperactivity of mesolimbic dopamine neurons may also

Answer

A

play a role in aggressive and hostile symptoms in schizophrenia and related illnesses.

Question 55

Q

Mesocortical dopamine pathway and cognitive, negative, and affective symptoms of schizophrenia arises from

Answer

A

cell bodies in the ventral tegmental area, but projecting to areas of the prefrontal cortex, is known as the mesocortical dopamine pathway.

Branches of this pathway into the dorsolateral prefrontal cortex are hypothesized to regulate cognition and executive functions.

Branches of this pathway into the ventromedial parts of the prefrontal cortex are hypothesized to regulate emotions and affect.

Many researchers believe that cognitive and some negative symptoms of schizophrenia may be due to a deficit of dopamine activity in mesocortical projections to the dorsolateral prefrontal cortex, whereas affective and other negative symptoms of schizophrenia may be due to a deficit of dopamine activity in mesocortical projections to the ventromedial prefrontal cortex.

Question 56

Q

Many researchers believe that cognitive and some negative symptoms of schizophrenia may be due to

Answer

A

A deficit of dopamine activity in the mesocortical projections to the dorsolateral prefrontal cortex, whereas affective and other negative symptoms of schizophrenia may be due to a deficit of dopamine activity in the mesocortical projections to the ventromedial prefrontal cortex.

Question 57

Q

The mesocortical dopamine pathway and cognitive, negative, and affective symptoms of schizophrenia arise from

Answer

A

cell bodies in the ventral tegmental area, but projecting to areas of the prefrontal cortex, is known as the mesocortical dopamine pathway.

Branches of this pathway into the dorsolateral prefrontal cortex are hypothesized to regulate cognition and executive functions.

Branches of this pathway into the ventromedial parts of the prefrontal cortex are hypothesized to regulate emotions and affect.

Many researchers believe that cognitive and some negative symptoms of schizophrenia may be due to a deficit of dopamine activity in mesocortical projections to the dorsolateral prefrontal cortex, whereas affective and other negative symptoms of schizophrenia may be due to a deficit of dopamine activity in mesocortical projections to the ventromedial prefrontal cortex.

Question 58

Q

Mesocortical dopamine pathways branching into the dorsolateral prefrontal cortex are hypothesized to

Answer

A

regulate cognition and executive functions.

Question 59

Q

Mesocortical dopamine pathways branching into the ventromedial parts of the prefrontal cortex are hypothesized to

Answer

A

to regulate emotions and affect.

Question 60

Q

Therapeutic Dilemma…

Answer

A

Theoretically, increasing dopamine in the mesocortical dopamine pathway might improve negative, cognitive, and affective symptoms of schizophrenia. However, since there is hypothetically an excess of dopamine elsewhere in the brain – within the mesolimbic dopamine pathway – any further increase of dopamine in that pathway would actually worsen positive symptoms.
How does one increase dopamine in the mesocortical pathway while simultaneously decreasing dopamine activity in the mesolimbic dopamine pathway? Enters the Atypical Antipsychotics -

Question 61

Q

Glutamate Hypothesis and NMDA Receptor Hypofunction Hypothesis

Answer

A

Excess Glutamate
Decreased GABA
NMDA receptor antagonist PCP has been shown to induce the positive, negative, and cognitive symptoms of schizophrenia in healthy patients and cause a resurgence of symptoms in stable patients. These observations led to the NMDA receptor hypofunction hypothesis as an alternative theory for the underlying cause of schizophrenia.

Question 62

Q

First Generation Antipsychotics (FGAs)

Answer

A

FGAs are also known as typical antipsychotics, conventional or classic antipsychotics, and dopamine receptor antagonists (DRAs)

FGAs reduce dopaminergic neurotransmission in the four dopamine pathways by blocking D2 receptors.

Although individual effects may vary from patient to patient, in general, conventional antipsychotics share the same primary mechanism of action and do not differ much in their therapeutic profiles. There are, however, differences in secondary properties, such as degree of muscarinic, histaminergic, and/or alpha adrenergic receptor antagonism, which can lead to different side-effect profiles.

Largely effective for positive symptoms

Highly effective for all disorders that result in psychotic thought processes

Acute and chronic neurological side effects can limit their effectiveness

Relatively ineffective for negative symptoms

Start low and go slow

Be sure to review clinical guidelines in Kaplan & Sadock on page 622 paying attention to contraindications under the heading “Dosage & Clinical Guidelines.

Question 63

Q

FGAs differ in

Answer

A

potency & side effects, not necessarily effectiveness.

Question 64

Q

High-potency FGAs

Answer

A

haloperidol, fluphenazine

Answer 52

A

perphenazine, loxapine

Answer 53

A

chlorpromazine

Answer 54

A

Haloperidol (Haldol), Fluphenazine (Prolixin), Thioridazine (Mellaril), Trifluoperazine (Stelazine)

Answer 55

A

Tardive Dyskinesia (TD)

Answer 56

A

Benztropine or Trihexyphenidyl or Diphenhydramine

Answer 57

A

Diphenhydramine

Answer 58

A

try Trihexyphenidyl or Benztropine

Answer 59

A

Blockade of the dopamine receptors in the tuberoinfundibular tract results in the increased secretion of prolactin, which can result in breast enlargement, galactorrhea, amenorrhea, and inhibited orgasm in women and impotence in men. The SDAs, with the exception of risperidone (Risperdal), are not particularly associated with an increase in prolactin levels and may be the drugs of choice for persons experiencing disturbing side effects from increased prolactin release.

Stimulation of serotonin 2A receptors stimulates prolactin release. Since they have opposing effects on prolactin, adding serotonin 2A antagonism to dopamine 2 antagonism results in a neutral effect on prolactin and may relieve breast secretions caused by dopamine 2 antagonism alone.

Answer 60

A

Idiosyncratic reaction to dopamine antagonists (more common in patients who are antipsychotic-naive)

Capable of producing significant mortality

Has been reported with almost all D1 & D2 antagonists including non-psychotropics such as Metoclopramide.

Answer 61

A

From a clinical perspective:

“Atypical antipsychotic” is defined in part by the “atypical” clinical properties that distinguish such drugs from conventional antipsychotics.

Atypical antipsychotics have the clinical profile of equal positive symptom antipsychotic actions, but low extrapyramidal symptoms and less hyperprolactinemia compared to conventional antipsychotics.

They also have antidepressant actions alone and in combination with other antidepressants.

They are “atypical” from what is expected from a classical, conventional, first-generation antipsychotic.

Almost all of the agents with this atypical profile came after the introduction of clozapine, sometimes the atypical antipsychotics are also called second-generation antipsychotics.

From a pharmacological perspective:

Current atypical antipsychotics as a class are defined as serotonin–dopamine antagonists, with simultaneous serotonin 5HT2A receptor antagonism that accompanies D2 antagonism.

Pharmacologic actions in addition to 5HT2A antagonism that can hypothetically also mediate the atypical antipsychotic clinical profile of low EPS and less hyperprolactinemia with comparable antipsychotic actions include partial agonist actions at 5HT1A receptors and partial agonist actions at D2 receptors.

Atypical antipsychotics as a class have the most complicated pattern of binding to neurotransmitter receptors of any drug class in psychopharmacology, and no two agents have an identical portfolio.

Answer 62

A

The presumed antipsychotic effects of the SGAs are blockade of D2 dopamine receptors. Where the SGAs differ from older antipsychotic drugs is their higher ratio interactions with serotonin receptor subtypes, most notably the 5-HT2A subtype, as well as with other neurotransmitter systems.

Hypothesized that these properties account for the distinct tolerability profiles associated with each of the SGAs.

All SGAs have different chemical structures, receptor affinities, and side effect profiles. No SDA is identical in its combination of receptor affinities, and the relative contribution of each receptor interaction to the clinical effects is unknown.

Answer 63

A

Beyond antagonism of 5HT2A and D2 receptors, atypical antipsychotics interact with multiple other receptor subtypes for both dopamine and serotonin and have effects on other neurotransmitter systems as well. Receptor binding properties linked to various serotonin receptors including 5HT1A partial agonist actions and antagonism of 5HT1B/D, 5HT2C, 5HT3, and 5HT7 receptors. Additional mechanisms linked to antidepressant actions that are shared by various atypical antipsychotics include:

Serotonin and/or norepinephrine reuptake inhibition – Only quetiapine (Seroquel) has potency greater than its D2 binding, ziprasidone (Geodon) has weak binding at these sites.

Alpha-2 (α2) antagonism – The proven antidepressant mirtazapine is best known for α2 antagonism, but several atypical antipsychotics also have this action with variable degrees of potency, including essentially all the “pines” (higher potency especially for quetia pine [Seroquel] and cloza pine [Clozaril]) and “dones” (higher potency especially for risperi done [Risperidal]) as well as aripiprazole (Abilify).

Answer 64

A

All antipsychotics are effective for psychotic mania, but atypical antipsychotics appear to have greater efficacy for nonpsychotic mania, leading to the major hypothesis - D2 antagonism/partial agonism combined with 5HT2A antagonism.

Answer 65

A

Use of atypical antipsychotics for the treatment of various anxiety disorders is controversial. There are some studies which suggest efficacy of various atypical antipsychotics for generalized anxiety disorder, and to augment other agents for other anxiety disorders. Most controversial is their use in PTSD. The one caveat to this is the anecdotal use as well as clinical evidence for utility in various anxiety disorders is greatest for quetiapine (Seroquel).

Answer 66

A

The good - With short-term treatment, sedation is a desired therapeutic effect, especially early in treatment, during hospitalization, and when patients are aggressive, agitated, or needing sleep induction.

The bad - With long-term treatment, sedation is generally a side effect to be avoided because diminished arousal, sedation, and somnolence can lead to cognitive impairment. When cognition is impaired, functional outcomes are compromised.

Generally speaking, the pines are more sedating than the dones

Answer 67

A

Clozapine, quetiapine, olanzapine, and iloperidone. All other antipsychotics have moderate potency, except lurasidone, which has essentially no binding to H1

Answer 68

A

All atypical antipsychotics share a class warning for causing weight gain and risks for obesity, dyslipidemia, diabetes, accelerated cardiovascular disease, and even premature death.

Answer 69

A

clozapine, olanzapine

Answer 70

A

risperidone, paliperidone, quetiapine, iloperidone (weight only)

Answer 71

A

ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine

Answer 72

A

Olanzapine is one of the antipsychotics most associated with weight gain and metabolic risk and would not be a first-line option for patients who have a primary concern about metabolic issues.

Quetiapine can lead to weight gain and increased triglyceride levels and may be a second-line option if a primary concern is metabolic issues.

Risperidone can lead to weight gain and increased triglyceride levels and may be a second-line option if a primary concern is metabolic issues.

Ziprasidone in general seems to be weight neutral and has been shown to lower triglyceride levels. It is therefore a recommended choice for individuals for whom metabolic issues are a primary concern.

Answer 73

A

weight gain and metabolic risk and would not be a first-line option for patients who have a primary concern about metabolic issues.

Answer 74

A

weight gain and increased triglyceride levels and may be a second-line option if a primary concern is metabolic issues.

Answer 75

A

weight gain and increased triglyceride levels and may be a second-line option if a primary concern is metabolic issues. As well as glycomastica

Ziprasidone in general seems to be weight neutral and has been shown to lower triglyceride levels. It is therefore a recommended choice for individuals for whom metabolic issues are a primary concern.

Answer 76

A

weight gain and increased triglyceride levels and may be a second-line option if a primary concern is metabolic issues. As well as glycomastica

Ziprasidone in general seems to be weight neutral and has been shown to lower triglyceride levels. It is therefore a recommended choice for individuals for whom metabolic issues are a primary concern.

Answer 77

A

weight gain and increased triglyceride levels and may be a second-line option if a primary concern is metabolic issues. As well as glycomastica

Answer 78

A

weight neutral and has been shown to lower triglyceride levels. It is therefore a recommended choice for individuals for whom metabolic issues are a primary concern.

Answer 79

A

equal positive symptom antipsychotic actions, but low extrapyramidal symptoms and less hyperprolactinemia compared to conventional antipsychotics.

Answer 80

A

serotonin–dopamine antagonists, with simultaneous serotonin 5HT2A receptor antagonism that accompanies D2 antagonism

actions include partial agonist actions at 5HT1Areceptors

Answer 81

A

Only quetiapine (Seroquel) has potency greater than its D2 binding,

ziprasidone (Geodon) has weak binding at these sites.

Answer 82

A

The proven antidepressant mirtazapine is best known for α2 antagonism

Several atypical antipsychotics also have this action with variable degrees of potency, including

Essentially all the “pines” (higher potency especially for quetia pine [Seroquel] and clozapine [Clozaril])

And “dones” (higher potency especially for risperi done [Risperidal]) as well as aripiprazole (Abilify).

Answer 83

A

Generally speaking, the pines are more sedating than the ones

The good - With short-term treatment, sedation is a desired therapeutic effect, especially early in treatment, during hospitalization, and when patients are aggressive, agitated, or need sleep induction.

The bad - With long-term treatment, sedation is generally a side effect to be avoided because diminished arousal, sedation, and somnolence can lead to cognitive impairment. When cognition is impaired, functional outcomes are compromised.

Answer 84

A

Clozapine, quetiapine, olanzapine, and iloperidone.

All other antipsychotics have moderate potency, except lurasidone, which has essentially no binding to H1

Answer 85

A

called a psychotic episode. During a period
of psychosis, a person’s thoughts and
perceptions are disturbed and the
the individual may have difficulty understanding
what is real and what is not

Answer 86

A

misrepresentation of a “real” sensory stimulus

Answer 87

A

defined as the perception of an object or event (in any of the 5 senses) in the absence of an external stimulus, are experienced by patients with conditions that span several
fields.

Answer 88

A

are false beliefs based on incorrect inferences about an external reality that persists despite the evidence to the contrary;
these beliefs are not ordinarily accepted by other members of the person’s culture or subculture.

Answer 89

A

 A. Two or more of the following for at least a one-month (or longer) period of time, and at least one of them must be 1, 2, or 3:

 1. Delusions
 2. Hallucinations
 3. Disorganized speech

 4. Grossly disorganized or catatonic behavior
 5. Negative symptoms, such as diminished emotional expression

 C. Duration: Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least one month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in Criterion A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).

 D. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either (1) no major depressive or manic episodes have occurred concurrently with the active-phase symptoms, or (2) if mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness.

 E. The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition.

 F. If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month (or less if successfully treated).

Answer 90

A

 A. Schizoaffective disorder debut has an uninterrupted period of illness, during which
there is an episode of mood disorder (manic or major depressive disorder) concurrent with a schizophrenia episode characterized by 2 or more of the following symptoms present for a considerable part of a 1-month period:
* delusions
* hallucinations
* disorganized speech (e.g., frequent derailment or incoherence)
* grossly disorganized or catatonic behavior
* negative symptoms (i.e. affective
flattening, alogia, or avolition).

 B. During this time, there should be a period of at least 2 weeks with delusions and
hallucinations, in the absence of prominent mood symptoms during the lifetime duration of illness.

 C. Mood symptoms have been present for the majority of the total duration of the
active and residual period of illness

Answer 91

A

The presence of one or more delusions for a month or longer in a person who, except for the delusions and their behavioral ramifications doesn’t appear odd and is not functionally impaired

can be either

with non-bizarre delusions are about situations that could occur in real life, such as being followed, being loved, having an infection, and being deceived by one’s spouse

or

with bizarre delusions that are clearly implauable

Answer 92

A

The category of unspecified psychotic disorder includes psychotic symptomatology (i.e., delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior) about which there is inadequate
information to make a specific diagnosis or about which there is contradictory information, or disorders with psychotic symptoms that do not meet the
criteria for any specific psychotic disorder.

Answer 93

A

Genetic factors
The likelihood is correlated with first-degree or second-degree relative with schizophrenia; 50% concordance with monozygotic twins

Biochemical Factors
 Dopamine hypothesis of too much dopamine-unsure if too much release, too many dopamine receptors, hypersensitivity to dopamine receptors, or combinations
 Serotonin-too much?
 GABA-inhibitory affect preventing from regulation of dopamine and causing hyperactivity of dopaminergic neurons

Neuropathology
 Reduced volumes of gray matter and enlarged cerebral ventricles
 Reduced symmetry and reduced limbic system
 Anatomical abnormality of the pre-frontal cortex

Answer 94

A

 FGAs are also known as typical antipsychotics, conventional or classic antipsychotics, and dopamine receptor
antagonists (DRAs) *
 FGAs reduce dopaminergic neurotransmission in the four dopamine pathways by blocking D2 receptors.
 Although individual effects may vary from patient to patient, in general, conventional antipsychotics share the same primary mechanism of action and do not differ much in their therapeutic profiles.
 There are, however, differences in secondary properties, such as degree of muscarinic, histaminergic, and/or alpha adrenergic receptor antagonism, which can lead to different side-effect profiles.
 Largely effective for positive symptoms
 Highly effective for all disorders that result in psychotic thought processes
 Relatively ineffective for negative symptoms

Answer 95

A

Chlorpromazine (Thorazine)
Prochlorperazine (Compazine)
Perphenazine (Trilafon)
Trifluoperazine (Stelazine)
Fluphenazine (Prolixin)
Haloperidol (Haldol)
Loxapine (Loxitane)
Thioridiazine (Mellaril)

Answer 96

A

Acute psychotic episodes, schizophrenia,
and schizoaffective

Maintenance of schizophrenia and
schizoaffective disorders

Mania

Delirium and dementia

Substance-induced psychotic disorder

Delusional disorder

Depression with psychotic symptoms

Answer 97

A

 S: sedation/sunlight sensitivity skin effects/sexual side effects
 T: tardive dyskinesia
 A: anticholinergic effects & agranulocytosis
 N: neuroleptic malignant syndrome
 C: cardiac arrhythmias (orthostatic hypotension)
 E: extrapyramidal symptoms /akathisia endocrine effects - increased prolactin eye effects

Answer 98

A

 Akathisia, Acute Dystonic Reactions, Parkinsonism

 Chronic dopamine blockage can lead to Tardive Dyskinesia (TD)

 If develops EPS give Benztropine or Trihexyphenidyl or Diphenhydramine

 Propranolol more beneficial for akathisia

 If develops TD give Diphenhydramine, weak studies Vitamin E use, change to a different antipsychotic with less potential

Answer 99

A

Stooped posture
Shuffling gate
Rigidity
Bradykinesia
Tremors at rest
Pill-rolling motion of the hands

Answer 100

A

Facial Grimacing

Involuntary upward eye movement

Muscle spasms of the tongue, face, neck, and back (back muscle spasms cause the trunk to arch forward

Laryngeal spasms

Answer 101

A

Restlessness

trouble standing still

paces the floor

feet in constant motion, rocking back and forth

Answer 102

A

Protrusion and rolling of the tongue

sucking and smacking movements of the lips

chewing motion

facial dyskinesia

involuntary movements of the body and extremities

Answer 103

A

Duration to implement tx - Minutes-hours
Tx options - Benztropine or other anticholinergic PO or IM

Answer 104

A

Duration to implement tx - Days
Tx options - Benzodiazepine

Answer 105

A

Duration to implement tx - Days - Weeks
Tx options - Benzodiazepine, beta-blockers

Answer 106

A

Duration to implement tx - Long term
Tx options - Switch to atypical or clozapine, Vesicular Monoamine transporter 2 inhibitor

Answer 107

A

More common with high potency typical antipsychotics (rare with atypical antipsychotics); D2 blockade

Onset in hours to days after antipsychotic started or dose increased; 90% within first 5 days

Benztropine 1-2mg 1-twice /day (SE: dry
mouth, blurred vision, constipation, urinary retention, cognitive changes) Diphenhydramine 50mg/day

If severe, stop the medication and give
above agents IV or IV once or twice
to stop the dystonia; then prescribe
oral medication to prevent another
episode

Answer 108

A

Pseudo parkinsonism—drug induced Parkinson’s like disease (Tremor “pill rolling”, rigidity or cogwheeling, bradykinesia-(slow movement), shuffling gait; slurred speech, mask like face, stooped posture, drooling;
cognitive dulling, worse negative symptoms, worse depression.

*Decrease the dose or switch to a different
antipsychotic

*First-line meds: Benztropine 1-2mg once or twice per day;

*trihexyphenidyl 2-5mg once or twice per day; diphenhydramine 50mg /day

*Symptoms can occur at any time; usually occurs within 1-2 months after antipsychotic initiated; highest risk patients: female, older higher potency agents at higher doses

*If the patient is at high risk for parkinsonism—start benztropine (or one of the first-line agents) at
the same time as starting the antipsychotic
*Can discontinue the anticholinergic agent after several weeks; many patients will not need to remain on it long term

*Usually caused by typical agents. Atypical can cause this also. (Meds least likely to cause this: clozapine, quetiapine, and
ziprasidone.) *D2 blockade—disruption
of balance b/t dopaminergic vs cholinergic neurons

Answer 109

A

Sense of restlessness, appear fidgety, can’t sit still, rocking motion; can be inner sense of restlessness; can lead to agitation and suicidal ideation; appears in days to weeks after starting medication

High potency typical agents most likely to cause this (Haloperidol); atypical aripiprazole, asenapine, brexpiprazole, cariprazine, lurasidone, paliperidone, risperidone;
SSRIs/Buspirone); D2 blockade

First-line medications to treat:

*Propranolol-Start 10mg BID; can go up to 30mg-90mg daily in 2-3 divided doses (SE: dizziness, fatigue, syncope, low BP)

*Inderal LA—long-acting propranolol dosed once a day (60- 80mg daily)

*Benzodiazepines-any of them will work. (Eg Lorazepam 0.5mg to 1mg BID) or diazepam 10mg BID or more frequently as needed

Reduce dose of medication; switch to lower potency agent or different atypical agent

*Don’t mistaken akathisia with agitation for psych disorder symptoms; you may worsen akathisia. (Clozapine, quetiapine, and lurasidone cause no more akathisia than placebo)

Answer 110

A

First line med
Deutetrabenazine (Austedo)

DOSE
6mg BID for 1 week, then raise based on response by 3mg BID every week max
24mg BID; take with food

RISK
QTc prolongation,
insomnia, nasopharyngitis, possible depression, and suicidality

NOTES
These usually need to
ordered through a specialty
pharmacy ($6000/mth)

First line med
Valbenazine (Ingrezza)

DOSE
40mg QHS for 1 week,
then 80mg QHS with or
without food

RISK
QTc prolongation, sedation,
possible depression and
suicidality

Answer 111

A

Step 1
Prevention-minimizing antipsychotics in patients at risk. Risk factors: Age>50; h/o SUD, brain injury, diabetes, HIV+, female gender, mood disorders, African American race, and presence of EPS
* Minimize the dose and duration if taking an antipsychotic
* Can decrease duration in mood disorders/not likely in schizophrenia

Step 2
Taper off with first signs of TD; discuss risks/benefits to continued treatment with antipsychotic
* d/c dose-lower the dose every 2-4 weeks
* Can have ‘withdrawal dyskinesias’ with worsening dyskinesias for the first few months after med is stopped
* Can be permanent, 30-50% of cases can resolve with discontinuation.

Step 3
Switch- if discontinuation is not successful.
* Clozapine is the only antipsychotic that does not cause TD (Low level of D2 occupancy) (has other risks) (Quetiapine also has a low level of D2 occupancy & low EPS rates)
* Aripiprazole, and olanzapine may be good alternatives

Step 4
VMAT2 inhibitor—if tapering and switching do not work-attempt to treat TD
* Valbenazine (Ingrezza)—take 1 time a day (1 in 4 response rates) & deutetrabenazine
(Austedo) Take BID with food (1 in 7 response rates) (H/o causing depress/suicide in past—has black box warning for Huntington’s for suicidality )
* Reduces dopamine hypersensitivity ; Don’t worsen psychosis; actually have been helpful in past for treating psychosis (reserpine)
* Take 4-6 weeks to work; continue as long as patient is taking the antipsychotic; or TD will
return within a mth of d/c

Step 5
Second line agents- dopamine agents that address other pathways such as glutamate antagonist- amantadine-tx’s dyskinesias in Parkinson’s disease; Ginkgo is neuroprotective; benztropine can
worsen TD with his anticholinergic effects

Answer 112

A

NMS is a life-threatening emergency and is fatal in 10% of cases. It usually occurs later in
treatment but can occur earlier.

It is characterized by:
 Reduced consciousness
 Increased muscle tone
 Autonomic dysfunction (hyperpyrexia, hypertension, tachycardia, tachypnea, diaphoresis, and drooling)

*Treatment consists of early detection, discontinuation of antipsychotics, management of fluid balance, temp. reduction, and monitoring for complications.

Answer 113

A

Anticholinergics-decreases antipsychotic effect

Barbiturates-decreases antipsychotic concentrations

Carbamazepine-up to 50% reduction in antipsychotic concentrations

Cigarette smoking-Reduced plasma concentration of antipsychotic agents

Fluvoxamine-increases haloperidol and clozapine concentrations

Amphetamines-may exacerbate psychosis

Benzodiazepines-Respiratory depression, stupor, and hypotension

Clonidine-hypotension or hypertension-potentiate alpha effects

Valproate Acid-Increases half-life and levels

Answer 114

A

Range
1- 40mg daily Decanoate: 10-20 times
the previous oral dose/2 weeks

How to dose-
Oral: 1-15mg/day can give once daily
or divided doses; not more than
100mg/day

Answer 115

A

Range
1-20mg/day Decanoate: 12.5-100mg/2
weeks

How to dose
Oral: 0.5-10mg/day in divided doses:
max: 40mg/day

Answer 116

A

Range
200-800mg/day

How to dose -
Initial: dose increased until symptoms controlled

Answer 117

A

Range
60-100 mg/day in divided doses

How to dose -
Initial 20mg/day in 2 doses titrate
over 7-10 days to 60-100mg/day in 2-
4 doses; max: 250mg/day

Answer 118

A

Range
12-24mg/day; 16-64mg hospital pts.

How to dose -
Initial: 4-8 mg TID; 8-16mg BID-QID
hospital pts.; Max: 64mg/day

Answer 119

A

Range
15-20mg/ day

How to dose -
Initial: 2-5 mg/day BID

Answer 120

A

From a clinical perspective:
* “Atypical antipsychotic” is defined in part by the “atypical” clinical properties that distinguish such drugs from conventional antipsychotics.

Atypical antipsychotics
Have the clinical profile of equal positive symptom antipsychotic actions, but low extrapyramidal symptoms and less hyperprolactinemia compared to conventional antipsychotics.
They also have antidepressant actions alone and in combination with other antidepressants.
Beyond antagonism of 5HT2A and D2 receptors, atypical antipsychotics interact with multiple other receptor subtypes for both dopamine and serotonin and have effects on other neurotransmitter systems as well
They are “atypical” from what is expected from a classical, conventional, first-generation antipsychotic.

Answer 121

A

 The presumed antipsychotic effects of the SGAs are blockade of D2 dopamine receptors.
 Where the SGAs differ from older antipsychotic drugs is their higher ratio interactions with serotonin receptor subtypes, most notably the 5-HT2A subtype, as well as with other neurotransmitter systems.
 Hypothesized that these properties account for the distinct tolerability profiles associated with each of the SGAs.
 All SGAs have different chemical structures, receptor affinities, and side effect profiles.
 Beneficial for both negative and positive symptoms.

Answer 122

A

Clozapine (Clozaril)

Risperidone (Risperdal)

Olanzapine (Zyprexa)

Quetiapine (Seroquel)

Ziprasidone (Geodon)

Aripiprazole (Abilify)

Paliperidone (Invega)

Asenapine (Saphris)

Iloperidone (Fanapt)

Lurasidone (Latuda)

Brexpiprazole (Rexulti)

Cariprazine (Vraylar)

Answer 123

A

Schizophrenia

Behavioral disturbances with dementia

Treatment-resistant depression

Autism Spectrum Disorders

Post Traumatic Stress Disorder

Anxiety disorders

Adjunctive treatment of depression

Acute Mania

Answer 124

A

*Many of the same side effects of
FGAs-
one disadvantage of atypicals
is the tendency to gain weight and
put patients at risk for Metabolic
Syndrome which consists of :
(Weight gain, Dyslipidemia, Altered
glucose metabolism, & Hypertension)

Answer 125

A

Clozapine, Olanzapine

Answer 126

A

risperidone, paliperidone, quetiapine,
iloperidone (weight only)

Answer 127

A

ziprasidone, aripiprazole, lurasidone,
iloperidone (low for dyslipidemia), asenapine

Answer 128

A

Olanzapine is one of the antipsychotics most associated with weight gain and
metabolic risk
Quetiapine can lead to weight gain and increased triglyceride levels and may be a second-line options if a primary concern is metabolic issues
Risperidone can lead to weight gain and increased triglyceride levels and may be a second-line options if a primary concern is metabolic issues.
Ziprasidone in general seems to be weight neutral and has been shown to
lower triglyceride levels.

Answer 129

A

Blockade of the dopamine receptors in the tuberoinfundibular tract results in the increased secretion of prolactin, which can result in breast enlargement, galactorrhea, amenorrhea, and inhibited orgasm in women and impotence in men.
The SGAs, apart from risperidone (Risperdal), are not particularly associated with an increase in prolactin levels and may be the drugs of choice for persons experiencing disturbing side effects from increased prolactin release.
Stimulation of the serotonin 2A receptors stimulates prolactin release

Answer 130

A

Clozapine is the worst, then olanzapine, quetiapine, and risperidone, paliperidone (in descending order)
Other SGAs are close to a weight neutral in adults. Kids still tend to gain weight despite neutral meds
Weight gain and metabolic effects are the greatest in the pediatric population
All labels with FDA warning for weight gain, hyperglycemia, new-onset or worsening diabetes and
hyperlipidemia

Answer 131

A

Clozapine, olanzapine, quetiapine are most sedating. ‘Revved up psychosis” will do well on these.
May need an alternative antipsychotic for long-term treatment if too sedating

Answer 132

A

EKG changes-ziprasidone is most prevalent with increased QT interval and can cause serious arrhythmias
* Actual risk is only 0.06%.

Others that cause QT prolongation: are thioridazine (Mellaril), iloperidone (Fanapt),
quetiapine (Seroquel)

Answer 133

A

EPS among the FGAs—Haloperidol and fluphenazine (Prolixin) cause the most EPS
Among the SGAs: risperidone is the highest EPS risk

Answer 134

A

aripiprazole (Abilify) & brexpiprazole (Rexulti)

Answer 135

A

Depends on plasma levels; trough level of
350 ng/mL

25mg qhs; increase by 25-50mg every 48-72
hours as tolerated

Answer 136

A

15-30mg/day schizo and mania 2-10mg/day
augment depression Decanoate: 300-
400mg/ 4 weeks

Oral: 10-15mg/day initial; max: 30mg/day-
schizo/mania 2-5mg/day

Answer 137

A

2-8mg/day psychosis or bipolar
0.5-2mg/day for children and elderly
12.5mg-50mg IM every 2 weeks

1mg/day orally in BID; increase 1mg each day as tolerated

Answer 138

A

400-800mg/day- Schizo
300mg/day Bipolar Depression

25mg BID and increase by 25-50mg twice a
day each day; max: 800mg

Acute mania: 100mg day 1 and increase to 400mg/day on day 4

Answer 139

A

10-20mg/day

5-10mg/day increase by 5mg once a week until desired efficacy

Answer 140

A

40mg-200mg/day schizo;
80- 160mg/day Bipolar

Schizo: initiate 20mg BID with food/

Bipolar: initiate 40mg BID

Answer 141

A

6mg/day Sustenna: 39-234mg/month

6mg/day taken in the morning; increase by 3mg/day
every 5 days

Answer 142

A

10-20mg/day BID dose- Sublingual
Children: 5mg BID; max 10mg/day

10mg/day- do not eat or drink for 10 mins.
after

Answer 143

A

12-24mg/day in BID dosing

2mg/day 1; 4mg/day 2; 8mg/day 3,
12mg/day on day 4; 16mg day 5

Answer 144

A

40mg-80mg/day Schizophrenia
20-60mg/day Bipolar

Take with food; 40-80mg/day increase as
tolerated

Answer 145

A

2-4mg/day Schizo
2mg/day Depression

1mg/day on days 1-4;
2mg on day 5- 7, and
4mg day 8 if needed

Answer 146

A

1.5-6mg once daily Schizo 3-6mg/day
daily

1.5mg/day on day 1 and can increase to 3mg
day 2

Answer 147

A

 Contraindications of treatment- allergic response history, ingestion of substance that may interact with antipsychotic, severe cardiac abnormality, high risk for seizures, narrow angle glaucoma, and presence of TD.

 Usual assessment of CBC, LFTs, and EKG

 Elderly and children more sensitive to treatment

 Start low and go slow

 Maximal effects of particular dose may not be evident for 4-6 weeks

 First 3-6 mos. After a psychotic episode are usually considered period of stabilization- dosage can be decreased about 20% every 6 mos. Until minimum effective dose is found.

 Persons usually maintained on antipsychotic 1 to 2 years after first psychotic episode; usually 5 years after 2nd episode;
lifetime maintenance after 3rd psychotic episode

Answer 148

A

May overcome problems with compliance

IM preparations usually give every 1- 4 weeks

May have to adjunct with oral medications initially until dose is therapeutic

After 3 to 4 weeks injection dose can be increased to single dose equal to total dose of drug given during period

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Atypical & Typical Antipsychotics Flashcards

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