antipsychotics Flashcards
(122 cards)
1
Q
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DSM-5 Criteria for
Schizophrenia
A
2
Q
positive Symptoms of Schizophrenia
A
3
Q
negative Symptoms of Schizophrenia
A
4
Q
cognitive symptoms of Schizophrenia
A
5
Q
Proposed Pathophysiology of
Schizophrenia
*
A
- dopamine theory
6
Q
Dopaminergic Pathways
A
Nigrostriatal (A9)
Mesolimbic (A10)
Mesocortical (A10)
Tuberoinfundibular
7
Q
Nigrostriatal (A9) function
A
EP system - movement
8
Q
mesolimbic function
A
arousal, memory,
motivation
9
Q
mesocortical function
A
cognition,
communication,
social function,
response to stress
10
Q
tuberoinfundibular function
A
regulates prolactin
release
11
Q
Uses for Antipsychotics
* FDA Approved Indications
A
– Schizophrenia
– Bipolar Disorder
– Adjunctive Therapy in Major Depressive Disorder
– Autism Spectrum Disorder
12
Q
off label Uses for Antipsychotics
A
– Anxiety Disorders
– PTSD
– OCD
– Psychosis (other than schizophrenia)
– Acute treatment of aggression and agitation
13
Q
FGA – Mechanism of Action
diagram
A
postsynaptic d2 antagonism
14
Q
Effect of Nonselective Dopamine (D2) Antagonism of FGA
at dif D paths
A
15
Q
Dopaminergic Pathways – Effect of FGA on pathways
A
16
Q
FGA Efficacy and activity
A
- limited spectrum of efficacy/ activity, only tx’s psychosis
17
Q
Relative Potencies of FGA
A
halo= high and chlorpro=low
18
Q
what other receptors afre affects by FGAs
A
a1, M1, H1
19
Q
Adverse Effects by Receptor
Blockade at H1 due to FGA
A
dry mouth, drowsy
20
Q
Adverse Effects by Receptor
Blockade at M1 due to FGA
A
21
Q
Adverse Effects by Receptor
Blockade at alpha due to FGA
A
22
Q
Adverse Effects by Receptor
Blockade
* Dopamine antagonism
A
– Extrapyramidal Side Effects (EPS) – “movement disorders”
» Dystonic reaction
» Pseudoparkinsonism
» Akathisia
» Tardive dyskinesia
– Hyperprolactinemia –
» galactorrhea, menstrual irregularities /
amenorrhea, gynecomastia, sexual dysfunction
23
Q
Side Effect Profile - FGA: haloperidol
A
24
Q
Side Effect Profile - FGA: Chlopromazine
A
25
which FGA is more likely to have side effect associated with H, M and a receptors?
Chlopromazine
26
Extrapyramidal Side Effects (EPS) of antipsychotics
* acute dystonia
* pseudoparkinsonism
* akathasia
* tarditive dyskenisia
*
27
Extrapyramidal Side Effects (EPS):
Acute Dystonia
acute dystonic reaction - “severe muscle spasm”:
* eye-oculogyric crisis
* neck-torticollis
* back-retrocollis
* **tongue-glossospams**
*** pharyngeal-laryngeal dystonia**
28
incidence acute dystonia
2-64%
29
acute dystonia pathophys
mbalance between DA and ACh
30
acute dystonia onset
usually occurs during first 5 days of treatment or after a dosage increase
31
acute dystonia risk factors:
high potency AP, large doses, IM administration, young males
32
acute dystonia tx:
– acute treatment
– chronic treatment
– acute treatment - AC agent [ex. benztropine, diphenhydramine or a benzodiazepine
– chronic treatment - decrease dose, change AP agent, AC agent
33
Drugs to Treat Dystonia
| dental implication?
* Benztropine- IM
* Trihexyphenidyl-IM
* Diphenhydramine
Oral side effect – **dry mouth**
| Anticholinergic agenst target M1
34
Pseudoparkinsonism
signs
35
what aspects of pseudopark may influence dentistry
excessive drooling and rigidity/trembling of head
36
four cardinal symptoms of pseudoparkinsonism
– motor?
– tremor?
– rigidity?
– posture?
four cardinal symptoms
– akinesia, bradykinesia or decreased motor activity
– tremor
– cogwheel rigidity
– postural abnormalities
37
Pseudoparkinsonism incidence
15-36%
38
pseudopark pathophysiology:
decrease in DA activity
39
pseudopark onset
1-2 weeks after AP initiation or increase in dose
40
pseudopark risk factors
high potency AP, increased AP doses, age >40, female
41
tx pseudopark
treatment: decrease dose, change AP agent, AC agents [benztropine/Trihexyphenidyl], DA agonist [amantadine]
42
Drugs to Treat
Pseudoparkinsonism
| dental implications?
* Benztropine
* Trihexyphenidyl
Oral side effect – **dry mouth**
| M1 antagonists
43
Akathisia
* extreme motor restlessness/inability to sit still
– patient can not typically control akathisia for even a short time period
44
akathsia incidence
incidence: 25-36%
45
akathasia pathophys
pathophysiology: unknown
46
akathasia onset
onset: 2-4 weeks
47
Akathisia dif to distinguish from?
difficult to distinguish from anxiety/agitation/psychosis
– akathisia made worse with increased AP doses
48
akathasia risk factors
high potency AP, large AP dose
49
akathasia tx
treatment: decrease dose, change AP agent, **beta blocker
propranolol **, or a** benzodiazepine**
50
how can propranolol be useful for akathasia tx from a dental view
no oral side effect
51
Propranolol (Inderal)
* MOA
Propranolol (Inderal)
* MOA - nonselective
beta-adrenergic
receptor blocking
agen
| used for akathaisa
52
Propranolol:
* Common Side Effects
* life-threatening?
* oral side effects?
* Overdose?
* ddi?
* Common Side Effects
– Dizziness, weakness and fatigue
* No life-threatening side effects
* No oral side effects
* Overdose – hypotension and bradycardia
* High risk for drug interactions
53
Tardive Dyskinesia
* syndrome characterized by involuntary movements
* **– buccal-lingual-masticatory syndrome (BLM)- makes dental tx hard**
– orofacial movements
– writhing movements of face, neck, back, trunk and extremities
54
incidence tarditive dyskenesia
20%
55
tarditive dyskenesia pathophysiology
(1) increase in DA receptor sensitivity
(2) neuronal degeneration
56
tarditive dykenesia onset
yrs
57
tarditive dyskenesia risk factors
increased age, female, concurrent diagnosis of mood d/o, long duration of AP use
58
Tardive Dyskinesia Treatments:
* first step?
* dosages?
* AP agent?
* Rx's used?
* prevention
* reduce dose of AP – always use lowest effective dose
* change AP to second generation antipsychotic (SGA)
– clozapine -- treatment option
* * 2 drugs recently FDA approved for TD
– **MOA – vesicular monoamine transporter 2 inhibitor (VMAT2)**
» **Valbenazine **(Ingrezza)
* Oral side effect – dry mouth
» **Deutetrabenazine** (Austedo)
* Oral side effect – dry mouth
59
Oral Side Effects
* FGA's
60
Oral side effects of Medications to treat
side effects of FGA
61
CV Side Effects of FGA
62
Weight Gain and FGA
63
FGA advantages
– effective for positive symptoms
– multiple dosage formulations available
– decreased cost
64
* FGA Disadvantages
– not effective in 30% of patients
– minimal efficacy for negative symptoms
– minimal efficacy for cognitive symptoms
– high side effect burden (EPS)
– risk of tardive dyskinesia
– nonadherence
65
SGA – Mechanism of Action
Selective Dopamine (D2) Antagonism and Serotonin Antagonsim (5 -HT2A) of SGA
66
Advantages of SGA different moa
Advantages of Selective Dopamine (D2) Antagonism and Serotonin Antagonsim (5-HT2A) of SGA
block of 5ht works to increase DA in non-mesolimbic paths to prevent ADRs
67
Dopaminergic Pathways – Effect of SGA's at the pathways
68
clozapine:
69
Risperidone
70
Olanzapine (OLZ)
71
Quetiapine (QUE)
72
Aripiprazole (ARI)
73
Lurasidone (LUR)
74
SGA and side effect burden
75
clozapine receptors acted on
76
clozapine indications
– Treatment refractory schizophrenia
» Lack of efficacy
» Intolerable side effects (i.e. TD)
– ↓ risk of recurrent suicidal behavior in schizophrenia and schizoaffective disorde
77
# which SGA has the greatest potential for binding other receptors?
(not D2/5HT)
clozapine
| olanzapine high as well but a little less with a/M
78
clozpaine
– CBC?
– dose related risk of?
– cv
– oral effects?
– agranulocytosis, must be monitored
– dose related seizure risk
– myocarditis
– oral side effects
» dry mouth, sialorrhea, hypersalivation; could cause either
79
Receptor Binding Affinities
Reflecting Side Effect Profiles of clozapine
high action at all 3
80
metabolic effects of clozapine
highest, these are MC of mortality
81
Risperidone receptors acted on
82
Risperidone (Risperdal)
* Indications
– Schizophrenia
» Acute treatment
* Adults + adolescents 13-17 years
» Maintenance treatment
– Bipolar I Disorder
» Acute Manic or Mixed Episodes – monotherapy or in combination with lithium or VPA
* Adults + children and adolescents 10-17 years
– Autism
» Treatment of irritability associated with autistic disorder in children and adolescents (ages 5-16 years)
» Symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods
83
Risperidone
* Additional information
– doses > 6 mg/day = ?
– prolactin?
– oral?
– doses > 6 mg/day = increase risk of EPS
– ↑ prolactin - not dose related
– no oral side effects
84
Receptor Binding Affinities
Reflecting Side Effect Profiles of risperidone
only action at a= hypo
85
Metabolic Side Effects of risperidone
moderate risk
86
Olanzapine receptors affected
87
Olanzapine (Zyprexa)
* Indications
– Schizophrenia
» Acute treatment
* Adults and adolescents 13-17 years
» Maintenance treatment
– Bipolar I Disorder
» Acute Manic or Mixed Episode – monotherapy or combination with lithium or VPA
* Adults and adolescents 13-17 years
» Maintenance treatment – monotherapy
» Depressed Episodes - combination product only (Symbyax - olanzapine+ fluoxetine)
– Treatment Resistant Major Depressive Disorder – combination product only (Symbyax – olanzapine + fluoxetine)
» Defined as nonresponse to 2 separate trials of different antidepressants of adequate dose and duration in the current episode
– Acute agitation associated with schizophrenia or Bipolar I mania (IM formulation only
88
Olanzapine oral effects?
xero
89
Receptor Binding Affinities
Reflecting Side Effect Profiles of olazapine
high actions at all three
90
Metabolic Side Effects of olazapine
high risk
91
Quetiapine receptors affected
92
Quetiapine (Seroquel and Seroquel XR)
* Indications
– Schizophrenia
» Acute treatment
» Maintenance Treatment
– Bipolar I Disorder
» Acute Manic of Mixed Episodes – monotherapy or in combination with lithium or VPA
» Depression (Bipolar I and II disorder)
» Maintenance
– Adjunctive Treatment of Major Depressive Disorder (inadequate response to antidepressant monotherapy
93
Quetiapine
Oral effect?
– off label uses?
Oral side effect – dry mouth
– Commonly used off-label as a sedative hypnotic and anxiolytic
94
Receptor Binding Affinities
Reflecting Side Effect Profiles of quetapine
high effects at h1: WG and xero
moderate at a1: hypotension
95
Metabolic Side Effects of quetiapine
moderate
96
Aripiprazole targeted receptors
97
Aripiprazole (Abilify)
* Mechanism of action
– **D2 partial agonist**; can increase DA in def paths and decrease in path with too much
– 5HT2a antagonist
98
Aripiprazole indications
– Schizophrenia (Adults + adolescents 13-17 years)
» Acute treatment
» Maintenance treatment
– Bipolar Disorder I (Adults + children/adolescents 10-17 years)
» Acute Manic or Mixed Episodes – monotherapy or in combination with VPA or lithium
» Maintenance treatment
– Adjunctive treatment of Major Depressive Disorder (inadequate response to antidepressant monotherapy)
– Autism
» Treatment of irritability associated with autistic disorder in children and adolescents (ages 5-16 years)
» Symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods
99
Aripiprazole
– mc EPS?
– oral?
– akathisia is more common than other types of EPS
– no oral side effects
100
Receptor Binding Affinities
Reflecting Side Effect Profiles of aripriprazole
well tolerated
101
Metabolic Side Effects of aripiprazole
low
102
Lurasidone (Latuda) indications
– Schizophrenia
» Acute treatment
– Depressive episodes associated with Bipolar I disorder
103
Lurasidone
– Must be taken with?
– oral?
– Must be taken with food (at least 350 kcal)
– No oral side effects
104
Receptor Binding Affinities
Reflecting Side Effect Profiles of Lurasidone
well tolerated
105
Metabolic Side Effects of Lurasidone
low risk
106
Oral Side Effects of SGA's
* Sialorrhea, Hypersalivation?
* Dry Mouth?
| which agents can cause these? why?
* Sialorrhea, Hypersalivation
– Clozapine (Clozaril)
* Dry Mouth
– Clozapine (Clozaril)
– Olanzapine (Zyprexa)
– Quetiapine (Seroquel
| due to blocking action at h1or m1 (xero)
107
CV Side Effects of SGA's scale
108
SGA advantages
– effective for?
– may be effective for?
– clozapine effective in treatment of?
– side effect profile?
» decreased risk of?
» decreased incidence of ?
» prolactin? exception>/
– effective for positive symptoms
– may be effective for negative symptoms
– clozapine effective in treatment refractory schizophrenia
– improved side effect profile as compared with FGA
» decreased risk of TD
» decreased incidence of EPS
» minimal to no prolactin elevation (except RIS
109
SGA disadvantage
risk of metabolic side
effects
110
Selection of Antipsychotic Therapy
| what is first line for schizophrenia?
* Second Generation Antipsychotics (with the **exception of clozapine, olanzapine, and iloperidone**) have become the agents of first choice for the treatment of schizophrenia.
– Practice guidelines and consensus statements support this recommendation.
111
Maintenance Antipsychotic Therapy
* Relapse rates
* Relapse rates are extremely high
– 60-80% relapse rate within 1 year with no antipsychotic therapy
– 20% relapse rate within 1 year with continued antipsychotic therap
112
Treatment duration antipsychotics:
1st episode -
2nd episode -
> 2 episodes -
1st episode - treat x 1 year
2nd episode - treat x 5 years
> 2 episodes - treat for lifetime
113
initial response to AP and maximal response timeframes
Expect to see initial improvement in symptoms within 2 weeks of starting antipsychotic therapy.
Maximum response make take up to 6-8 weeks.
114
which SGA have the greatest chances of metabolic ADR
| Weight Gain, Risk for Diabetes, Worsening of lipid profiles
clozapine/olanzapine
115
which SGA are least likely to interact with extra receptors
Aripiprazole
Lurasidone
116
which SGA are least likely to cause metabolic disturbances
Aripiprazole
Lurasidone
117
which SGA may only affect a receptors additionally?
risperidone
118
which SGA have moderate effects on metabolic state
risperidone
quetiapine
119
which SGA do not affect M receptors
Risperidone
Quetiapine
Aripiprazole
Lurasidone
120
which SGA do not affect H receptors
Risperidone
Aripiprazole
Lurasidone
121
VMAT 2 inhibitors used for? ADE?
velbenzamine and debueterbenzamine
used for tarditive dyskensia
can cause xerostomia
122
which SGA may not prevent prolactin increase?
risperidone
