Antipsychotics Flashcards
1
Q
Lithium MOA
(we don’t actually know, but what is the hypothesis)
A
Depletes inositol → stops signal transduction → decreases hyperexcitatory state → decreases mania (will do NOTHING to a healthy person)
(3 strategies: block recycling, stop transporter, increase CREB to increase BDNF & Bcl-2)
2
Q
Lithium facilitates ______ neurotransmission & inhibits ______ excitatory neurotransmission
A
- inhibitory (GABA)
- excitatory (Glu & DA)
3
Q
Neuromuscular adverse effects of lithium (3)
A
- Tremor
- Muscle hyperirritability ataxia
- Extrapyramidal symptoms
4
Q
Lithium cardiac adverse effects (3)
A
- Arrhythmia
- Hypotension
- Peripheral circulatory collapse
5
Q
Lithium effect on chronic kidney disease: symptoms
A
Nephrogenic diabetes insipidus (including polyuria, thirst and polydipsia)
6
Q
Lithium may cause ________ (metallic or salty taste).
A
dysgeusia/taste distortion
7
Q
Lithium may cause which thyroid abnormalities?
A
- Euthyroid goiter and/or hypothyroidism (including myxedema)
- Lower T3 & T4
8
Q
______ is used in patients with low leukocyte counts.
A
lithium
(it will always be present during lithium treatment, so it is used off-label for this purpose)
9
Q
Lithium is primarily excreted by _______.
A
kidneys
(proportionately to serum concentration; 80% reabsorbed via passive diffusion)
10
Q
Haloperidol and lithium may cause ______
A
Encephalopathic syndrome
11
Q
Lithium may prolong the effects of _______ agents
A
neuromuscular blocking
12
Q
Lithium and diuretics or angiotensin-converting enzyme inhibitors may decrease _____
A
clearance of lithium
13
Q
Atypical antipsychotics may produce more severe ________ (AE) when combined with lithium.
(exeption: Clozapine)
A
extrapyramidal syndrome
14
Q
Lithium contraindications (3)
A
- renal disease
- cardiovascular disease
- Bradycardia - tachycardia syndrome (“sick sinus”)
15
Q
Therapeutic overdoses are usually due to the accumulation of lithium. This is usually caused by changes to the patient’s status such as _______ (3).
A
- Diminished serum sodium
- Use of diuretics
- Fluctuating renal function
16
Q
A value of over of _____ serum concentration is considered lithium toxicity.
A
2 mEq/L
17
Q
Which type of dialysis is preferred for treating lithium toxicity / overdose?
A
Hemodialysis
(peritoneal dialysis may also be used)
18
Q
In addition to treating bipolar (mainenance & mania) and cyclic depression, lithium may be used as _______ adjunct therapy.
A
unipolar depression
19
Q
List 4 mood stabilitzers that treat acute mania and/or bipolar maintenane
A
- Lithium
- Valproate
- Carbamazepine
- Lamotrigine
20
Q
Schizophrenia is typically diagnosed in which age group?
A
- Females: Early 20s to early 30s
- Males: Late adolescence to early 20s
(in general, late teens to early thirties : this is the age where ppl start to use their pre-frontal cortex more and symptoms start to appear)
21
Q
What are the three categories of schizophrenic symptoms?
A
- Positive
- Negative
- Cognitive
22
Q
Positive symptoms of schizophrenia are psychotic behavior is not seen in _____
A
Healthy people
23
Q
Schizophrenia: positive symptoms observed in patient
A
- Altered perceptions
- Abnormal thinking
- Odd behaviors
24
Q
Schizophrenia: positive symptoms the individual experiences
A
- Hallucinations
- Delusions
- Thought disorder (unusual thinking & disorganized speech)
25
Mesocortical pathway is associated with _______ symptoms of schizophrenia.
negative
(DA influences preception, cognition & social behavior)
26
Altered Perceptions in schizophrenia: they experience changes in _____ (5)
1. Vision
2. Hearing
3. Smell
4. Taste
5. Touch
27
Example of delusions experienced by schizophrenic patients (positive symptoms) (2)
1. Paranoia or irrational fears that others are " out to get you"
2. Believing that the television, radio or Internet are broadcasting special messages that require your response
28
Negative symptoms of schizophrenia: (5)
1. Loss of motivation
2. Disinterest or lack of enjoyment in daily activities
3. Social withdrawal
4. Flat affect
5. Reduced speech
29
Cognitive symptoms of schizophrenia include problems with _____ (3).
1. Attention
2. Concentration
3. Memory
30
Cognitive symptoms of schizophrenia: patients typically experiences difficulties with ______ (3)
1. Processing information to make decisions
2. Using information immediately after learning it
3. Focusing and paying attention
31
\_\_\_\_\_\_\_ (5) are commonly seen in patients with schizophrenia and can exacerbate the symptoms of their disorder.
1. Anxiety
2. Depression
3. Panic
4. OCD
5. Substance abuse (EtOH, tobacco, prescription meds)
32
Schizophrenia: goals of treatment are to *decrease* dopamine in the _________ pathway and *increase* DA in the \_\_\_\_\_pathway, simultaneously.
1. mesolimbic
2. mesocortical
(we do NOT want to block nigrostriatal or tuberoinfundibular DA pathways)
33
While treating schizophrenia, the goal is to *decrease* DA in the mesolimbic & *increase* DA mesocortical pathways and NOT the _____ (2) pathways.
1. Nigrostriatal
2. Tuberoinfundibular
34
First generation antipsychotics are antagonists at which receptors (5)?
(classes are phenothiazines & non-phenothiazines)
1. D2
2. M1
3. H1
4. alpha 1
5. alpha 2
35
Second generation antipsychotics are antagonist of which receptors?
5-HT2A / D2 antagonist / partial agonist (Inverse agonist)
(examples: Paliperidone, Risperidone, Pimavanserin)
36
Disadvantages of Chlorpromazine
many adverse effects (especially autonomic)
(class: phenothiazine)
37
Disadvantages of Olanzapine (2)
1. Weight gain
2. Dose-related lowering of seizure threshold
(class: Thienobenzodiazepine)
38
Disadvantage of Ziprasidone
QT Prolongation
(class: dihydroindolone)
39
What are the excitatory NTs in the brain?
1. Glu
2. DA
(lithium blocks these and increases GABA)
40
Mesolimbic pathway is associated with _______ (2) symptoms of schizophrenia.
delusions and hallucinations
41
Substance abuse disorder is commonly seen in schizophrenic patients. Why?
DA receptors are unavailable. They self-medicate to feel good.
(EtOH, smoking, prescription meds)
42
Why is dosage titration important?
If you get over 85% receptor-binding, side effects will begin to show up
43
Chlorpromazine Adverse Effects (8)
1. Sedation
2. Anticholinergic effects
3. Orthostatic hypotension
4. QT prolongation
5. Deposits in cornea & lens of eye
6. Photosensitivity
7. Hyperglycemia
8. Weight gain
(Others: SLE cells, False positive pregnancy tests,Tardive dyskinesia)
44
Adverse effects of fluphenazine (5)
1. Akathisia
2. Parkinsoniaism
3. Dystonia
4. Tardive dyskinesia
5. Prolactin elevation
45
Haloperidol adverse effects: akathisia, parkinsonism, ______ (5)
1. EPS: Dystonia, Tardive dyskinesia
2. Hyperprolactinemia
3. Face edema
4. QT prolongation
5. Photosensitivity, hyperhidrosis
(same as Fluphenazine + QT prolongation)
46
Thioridazine adverse effects (5)
1. Sedation
2. Anticholinergic effects
3. Orthostatic hypotension
4. Retinitis pigmentosa (dose-dependent)
5. Ventricular arrythmias
47
Thiothixene adverse effects (5)
1. EPS: Akathisia, Parkinsonism, Dystonia, Tardive dyskinesia
2. Elevated prolactin levels
(as fluphenazine and haloperidol)
48
Pimozide adverse effects (4)
1. Akathisia
2. Parkinsonism
3. Tardive dyskinesia
4. Prolactin elevation
49
Blockade of D2 receptors in the mesolimbic pathway helps to reduce positive symptoms of schizophrenia but also shut down the reward pathway leaving patients with the following symptoms (3).
1. Apathy
2. Anhedonia
3. Lacking motivation, interest and joy from social interactions
(similar to the negative symptoms of schizophrenia)
50
Neuroleptic - induced deficiency syndrome
Blocking D2 receptors in the music cortical pathway can worsen negative and cognitive symptoms (even tho low density of D2 receptors in the cortex)
51
Prolactin elevation from blocking D2 receptors in the tuberoinfundibular may lead to ______ (symptoms).
1. Hyperprolactinemia → galactorrhea and am in area
2. Fertility issues in women → rapid demineralization of bone in postmenopausal women, sexual dysfunction and weight gain
52
Tardive dyskinesia treatment (2)
1. Valbenazine
2. Deutetrabenazine
53
Chlormromazine indications (4)
1. schizo, mania, bipolar
2. childhood schizo & autism
3. N/V in terminal illness
4. Intractable hiccup
54
Chlorpromazine is used as an adjunct therapy for _____ (2)
1. short-term management of anxiety psychomotor agitation excitement
2. violent or dangerously impuslive behavior
55
Pharmacokinetics of ______ are complex; serum levels of unchanged drug and clinical effect do not correlate well.
Chlorpromazine
56
Clozapine also causes granulocytopenia or agranulocytosis in approximately 1% of patients requiring \_\_\_\_\_.
regular blood cell count monitoring
57
Clozapine is associated with excess risk of myocarditis and venous thromboembolic events including fatal pulmonary embolism. What are the other adverse affects (7)?
1. sedation
2. dizziness/vertigo
3. HA
4. tremor
5. hypersalivation, dry mouth
6. sweating
7. visual disturbances
58
\_\_\_\_\_\_ (second gen. antipsychotic) carries the greatest risk of QT prolongation
Ziprasidone
59
Quetiapine: prominent adverse effects (2)
1. Sedation
2. Hyperlipidemia
60
Olanzapine prominent adverse effects: Weight gain, Glucose abnormalities, Hyperlipidemia, Hyperglycemia & diabetes mellitus, _______ (5).
1. NMS
2. Sedation
3. Extremity pain
4. Dry mouth
5. Orthostatic hypotension
61
In addition to weight gain glucose abnormalities and hyperlipidemia, what are three other prominent adverse effects of Clozapine?
Sedation
Orthostatic hypotension
62
Why do a typical antipsychotics help with EPS symptoms?
blocks 5HT2A receptor → increases DA release
63
5-HT2A antagonism → increase DA neurotransmission in the Nigrostriatal pathway, reducingEPS. 5-HT1A partial agonism helps increase DA release in ____ and inhibit _____ release.
* PFC
* glutamate
(Hyperpolarization of cortical pyramidal cells produce anxiolytic effects. Improve negative and cognitive symptoms by increasing dopamine release in the prefrontal cortex)
64
Why do Clozapine and Quetiapine lower the risk of EPS?
They bind a more loosely to the D2 receptors
65
Clozapine is a substrate for which enzymes?
* CYP1A2
* CYP3A4
66
Olanzapine IM agitation is associated with ________ (2).
1. schizophrenia
2. bipolar I mania
67
Which second generation antipsychotics are D2 & 5HT2A antagonists?
1. Lurasidone
2. Olanzapine
3. Clozapine
68
Laruasidone (Latuda) indications
* Schizophrenia
* Depressive episodes associated with Bipolar I Disorder (bipolar depression) (as monotherapy and as adjunctive therapy with lithium or valproate)
69
Lurasidone (Latuda) metabolism mainly by _____ (enzyme).
CYP3A4.
(Grapefruit should be avoided, dose adjustment is needed in renal & hepatic impairment)
70
Cariprazine indications
* Schizophrenia
* Acute treatment of manic or mixed episodes associated with bipolar I disorder
(same as Lurasidone/Latuda)
71
Cariprazine AE (2)
1. EPS: akathisia
2. dyspepsia
3. Pregnancy: EPS and/or withrawal sx in neonates w/3rd trimester exposure
72
Cariprazine is metabolized extensively by ______ (enzyme) and weakly inhibits \_\_\_\_\_\_.
* CYP3A4
* CYP1A2, CYP2C9, CYP2D6, CYP3A4, CYP2C19, CYP2A6, and CYP2E1
73
Cariprazine MOA
* ***_Partial agonist_*** at the D3, D2 and 5-HT1A receptors
* Antagonist at 5-HT2B and 5-HT2A receptors
(no appreciable affinity for muscarinic receptors)
74
Which second generation antipsychotics are ***_Partial agonist_*** : 5-HT1A and D2 & Antagonist: 5-HT2A receptors
1. Brexpiprazole
2. Aripiprazole
75
Brexpiprazole AE
1. Suicide (\<24 y.o.)
2. Weight gain
3. Akathisia
4. Pathological gambling and other compulsive behaviors
76
Asenapine Indications:
* Schizophrenia
* Bipolar I disorder (Acute monotherapy of manic or mixed episodes, in adults and pediatric patients 10 to 17 years of age. Maintenance monotherapy treatment in adults)
77
Asenapine MOA
D2 and 5-HT2A receptor antagonist
78
Asenapine is metbolized via glucuronidation by _____ and oxidative metabolism by \_\_\_\_\_.
* UGT1A4
* CYP1A2
(weak inhibitor of CYP2D6)
79
Asenapine AE (3)
1. Seizure
2. Cognitive and motor impairment
3. QT prolongation
80
Aripiprazole (3rd gen. antipsychotic) Indications (6)
1. Schizophrenia
2. Agitation associated with schizophrenia or bipolar mania (Injection)
3. Acute treatment of manic and mixed episodes associated with Bipolar I
4. Adjunctive treatment of MDD
5. Irritability assoc. w/Autistic disorder
6. Tourette’s disorder
81
Aripiprazole & Brexpiprazole are BOTH metabolized by ______ & \_\_\_\_\_.
CYP3A4 and CYP2D6
(Dosage adjustments are recommended in patients who are known CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers)
82
Aripiprazole AE: Hyperglycemia, Dyslipidemia, DM, Weight gain, \_\_\_\_\_\_(4).
1. Seizure
2. Cognitive & motor impairment
3. NMS
4. Tardive dyskinesia
83
Neuroleptic Malignant Syndrome, aka \_\_\_\_\_\_\_, may be caused by almost any antipsychotic or tranquilizer (neuroleptic).
1. Drug-Induced Movement Disorder
2. Hyperthermia
3. Neuroleptic-Induced acute dystonia
84
Neuroleptic Malignant syndrom is caused by ______ antagonism
D2 receptor
85
Neuroleptic Malignant Syndrome symptoms
1. Fever (102 to 104 degrees F)
2. Irregular pulse
3. Tachycardia
4. Tachypnea
5. Muscle rigidity
6. Altered mental status
7. Autonomic nervous system dysfunction resulting in high or low blood pressure, profuse perspiration
8. Other symptoms may include liver or kidney failure, hyperkalemia, rhabdomyolysis or blood clots in veins and arteries
86
Neuroleptic Malignant Syndrome Tx (3)
1. Diazepam
2. Dantrolene
3. Bromocriptine
87
Why do antipsychotics also work for depression and other disorders
it has to do with the affinity for many receptors; at certain dosages it will have different effects (antidepression, sedation, etc)
