MT6314 ANTIPSYCHOTICS AND ANTIDEPRESSANTS Flashcards
1
Q
Study of the drugs that affect cognition, affect, and behavior of an individual
A
Psychopharmacology
2
Q
Psychopharmacology includes the study of what drugs?
A
Antidepressants
Antipsychotics
Classic Mood Stabilizers
Stimulants
Benzodiazepines
3
Q
What is psychosis?
A
Inability to distinguish between what is real and what is not real
4
Q
Psychosis involves?
A
̶ Delusions
̶ Hallucinations
̶ Disorganized thinking with clear sensorium
5
Q
What is the most common psychotic disorder?
A
Schizophrenia
6
Q
Schizophrenia is characterized by?
A
̶ Structural and functional changes in the brain
̶ Dysregulated neurotransmitters
7
Q
Neuronal Networks of Psychosis
A
Dopamine theory
NMDA theory
Serotonin theory
8
Q
NMDA theory effect on NMDA receptors?
A
- NMDA receptor hypofunction
9
Q
What neuronal pathway is the main reason behind Schizophrenia?
A
Dopamine pathway
10
Q
Serotonin theory is defined as?
A
- 5-HT2A receptor hyperfunction in the cortex
11
Q
Purpose of Antipsychotic drugs?
A
- Improve mood and reduce anxiety
12
Q
Type of antipsychotic drug with high incidence of EPS
A
Neuroleptic
13
Q
Classical drugs affinity?
A
D2»_space; 5-HT2 receptors
14
Q
Atypical / Newer agents affinity?
A
5-HT2»_space; D2 receptors
15
Q
Classes of older antipsychotics?
A
Phenothiazine
Thioxanthine
Butyrophenone
16
Q
Antipsychotics are well absorbed when administered ______
A
Orally
17
Q
Antipsychotics are lipid or water soluble?
A
Lipid
18
Q
Antipsychotics are extensively bound to?
A
Plasma proteins
19
Q
Antipsychotics have long or short half lives?
A
Long
20
Q
Parenteral forms of antipsychotics?
A
- Fluphenazine
- Haloperidol
- Ziprasidone
- Olanzapine
- Aripiprazole
21
Q
Schizophrenia is due to excess of what in where?
A
functional DA in mesocortical tracts in the brain
22
Q
Types of Dopamine receptors
A
̶ GPCR, D1-D5
23
Q
Location of D2 receptors?
A
in the caudate, putamen, cortex, hypothalamus – negatively coupled to adenylyl cyclase
24
Q
Blockade of D2 receptors leads to?
A
EPS (tremor, slurred speech, akathisia, dystonia)
25
Has affinity for other receptors and less EPS
* Atypical antipsychotics
26
All antipsychotic drugs block H1 receptor to some degree except?
̶ Haloperidol
̶ Iloperidone
̶ Lurasidone
27
Antagonist for D2 blockade?
Clozapine
28
Weak agonist for D2 blockade?
Olanzapine (+)
Quetiapine (+)
Aripiprazole (+)
Brexipiprazole (+)
29
Agonist for D4 blockade?
Haloperidol (+)
Iloperidone (+)
Asenapine (++)
Clozapine (++)
Aripriprazole (+)
Brexipriprazole (+)
30
Antagonist for alpha1 blockade?
Lurasidone
Cariprazine
31
Antagonists for 5-HT2 blockade?
Haloperidol
Molindone
32
Agonists for M blockade?
Most phenothiazines and thioxanthenes (+)
Thioridazine (+++)
Molindone (+)
Paliperidone (+)
Clozapine (++)
Olanzapine (++)
Quetiapine (+)
33
Antagonists for H1 blockade?
Haloperidol
Iloperidole
Lurasidone
34
Effect is dopamine receptor blockade
First generation drugs
35
Underlies antipsychotic effect
Mesocortical-mesolimbic path
36
Antiemetic effect in the Mesocortical-mesolimbic path due to?
blockade of the chemoreceptor trigger zone
37
Common adverse effects in first generation antipsychotics?
̶ Extrapyramidal symptoms, hyperprolactinemia (1st Generation)
38
Clinical use of antipsychotics?
* Treatment of schizophrenia
* Mania
* Tourette syndrome
* Alzheimers and Parkinsonism
39
How long do effects of antipsychotics take for treating Schizophrenia?
Effects take several weeks to develop
40
lower cost, EPS
1st gen
41
improves negative symptoms (emotional blunting,
social withdrawal, lack of motivation)
2nd gen
42
For treating mania, antipsychotics should be given with?
lithium
43
For treating mania, 2nd generation antipsychotics should be given with?
benzodiazepines
44
Drugs for prevention of manic phase of bipolar disorder
o Aripiprazole, olanzapine, asenapine
45
Drugs for prevention of bioplar depression
o Quetiapine, lurasidone, olanzapine, carizapine
46
Drugs for Tourettes syndrome
Molindone
47
What develops Parkinson-like symptoms?
Dose-dependent EPS
48
Dose-dependent EPS is common with?
Common with Haloperidol and more potent piperazine derivatives (Fluphenazine, trifluoperazine)
49
Dose-dependent EPS is infrequent with?
2nd generation drugs, Clozapine
50
Methods to deal with dose-dependent EPS?
Mx: reduce dose, use of antimuscarinic agents
51
Other neurologic dysfunction in the toxicity of antipsychotics are seen in?
akathisia, dystonias
52
Instances of akathisia, dystonias respond to?
Also respond to antimuscarinic agents, or diphenhydramine
53
Why do the autonomic effects of toxicity occur?
̶ Due to blockade of peripheral muscarinic and alpha receptors
54
Order of strength of autonomic effects?
Thioridazine>>clozapine and atypicals>>haloperidol
55
Atropine like effects are ? and treated by?
Dry mouth, constipation, urinary retention – Thioridazine and Chlorpormazine
56
Caused by alpha blockade
Postural Hypotension
57
Choreoathetoid movements of the lip and buccal muscle
Tardive dyskinesia
58
Is tardive dyskinesia reversible?
May be irreversible
59
What increases severity of the symptoms in tardive dyskinesia?
Antimuscarinic drugs that improve EPS
60
T or F: Switching to Clozapine for treating tardive dyskinesia improves the condition
F, does not exacerbate only
61
How to temporarily improve the condition of tardive dyskinesia?
increasing neuroleptic dosage
62
Endocrine effects in antipsychotic toxicity?
Hyperprolactinemia, gynecomastia, infertility due to D2 blockade in pituitary, prominent with Risperidone
63
Who are prone to NMS?
Patients sensitive to the EPS
64
How to treat NMS?
̶ Treat with dantrolene, diazepam, dopamine agonists
65
Sedation in antipsychotic toxicity is marked in what drug?
Chlorpromazine
66
Least sedating antipsychotics?
fluphenazine and haloperidol; aripiprazole and lurasidone
67
Visual toxicities for antipsychotics?
̶ Visual: retinal deposits with thioridazine
68
Cardiac effects of antipsychotic toxicity?
̶ Cardiac rhythm abnormalities: thioridazine, quetiapine, ziprasidone
69
What causes agranulocytosis and seizure a high doses?
Clozapine
70
Commonly used for manic phase of bipolar disorder
Lithium
71
Why is important to monitor levels of lithium in the plasma?
to establish effective and safe dosage
72
MOA of lithium?
- inhibits enzymes for recycling neuronal membrane phosphoinositides
- depletion of PIP2 , IP3, DAGs
- prevents amine neurotransmission
73
Antiseizure drugs include?
̶ Valproic acid
̶ Carbamazepine and lamotrigine
74
Valproic acid prolongs inactivation of?
voltage gated Na channels, GABAA agonist
75
Used for antimanic effects when failed to respond to lithium
̶ Valproic acid
76
Prolongs inactivation of voltage gated Na channels
̶ Carbamazepine and lamotrigine
77
Carbamazepine and lamotrigine are used for?
for mania and prophylaxis of depressive phase
78
Half life of lithium?
20hrs
79
How is lithium distributed?
Body water
80
Therapeutic dosage of lithium?
0.6-1/4 mEq/L
81
Increases renal clearance
Theophylline
82
Treatment for increased lithium at toxic levels
Thiazide diuretics
83
Why is lithium required at the initiation of treatment?
Slow onset of action
84
Lithium can increase what anomaly?
Ebstein's anomaly (congenital cardiac anomaly)
85
What drugs are under phenothiazines?
Chlorpromazines
Fluphenazine
Thioridazine
86
Phenothiazines block what receptors?
alpha
M
H1
87
What drug is under butyrophenones?
Haloperidol
88
MOA of butyrophenones?
Blocks D2 > 5-HT2 receptors
89
What receptors to butyrophenones block?
Some for alpha
Less for M
90
Antipsychotic drug class used in Huntington chorea and Tourettes
Butyrophenones
91
MOA of second generation antipsychotics
Block 5-HT2 > D2
92
Feelings of sadness and or loss of interest in normally
pleasurable activities, leading to emotional and physical problems, with resulting impairment in social, occupational and other areas of functioning for 2 weeks
depression
93
Hypotheses for antidepressants?
Monoamine hypothesis
Neurotrophic hypothesis
Neuroendocrine hypothesis
94
TCAs are related to?
phenothiazine antipsychotics
95
TCAs route of administration
Orally
has 1st pass effect
96
What kind of metabolism required for TCAs?
* Excessive hepatic metabolism required
97
Short or long half life for TCAs?
Long
98
Fluoxetine long or short half life?
Long (1 dose/ week)
99
Heterocyclics have Pharmacokinetics similar to ?
TCA
100
Heterocyclics that have short half lives
Nefazodone and trazodone
101
Related to amphetamines and orally active
Monoamine oxidase inhibitor
102
metabolizes NE, Epinephrine, Serotonin
MAOI-A
103
metabolizes Dopamine, Tyramine
MAOI-B
104
MAOI with fastest onset, short duration of action
Tranylcypromine
105
What class drug: Phenelzine, Selegiline, Tranylcypromine
MAOIs
106
What class drug: Amoxapine, Bupropion, mirtazapine
Heterocyclic antidepressants
107
WHAT CLASS DRUG: Duloxetine, venlafaxine
5-HT-NE reuptake inhibitors
108
WHAT CLASS DRUG: Nefazodone, Trazodone
5-HT antagonists
109
WHAT CLASS DRUG: Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline
Selective Serotonin reuptake inhibitors
110
WHAT CLASS DRUG: Amitryiptyline, Clomipramine, imipramine
TCA
111
Neuroendocrinic factors include?
ACTH
Sex steroids
Thyroid hormone
112
During depressed states, what happens with the thyroid hormone?
Blunting of response of thyrotropin and thyrotropin-releasing hormones, elevations in thyroxine
113
ACTH effect in depression
Nonsupression of ACTH in the dexamethasone suppression test
114
Other drugs with antidepressant action
Ketamine
Brexanolone
115
NMDA antagonist
Ketamine
116
Nasal spray version of ketamine
Esketamine
117
modulator of GABA A receptors
Brexanolone
118
Use of brexanolone
PPD
119
Inhibit SERT
SSRIs
120
6 major SSRIs
Fluoxetine
Sertraline
CItalopram
Paroxetine
Fluvoxamine
Escitalopram
121
S enantiomer of citalopram
Escitalopram
122
Not optically active
Paroxetine
Fluvoxamine
123
Indications of SSRIs
GAD
PTSD
OCD
Panic disorder
PMDD
124
Half life of SSRIs
18-24hrs
125
SSRIs have minimal inhibitory effects on?
NE
126
Bind to transporters for both serotonin and NE
SNRI
127
TCA MOA?
Inhibit the reuptake transporters that terminate the
actions of NE and 5-HT and blocks H receptors and α-adrenoceptors
128
blocks 5HT2A receptor in the neocortex
Nefazodone and trazodone
129
MAOI MOA?
Increase brain amine levels, interfering with metabolism --> increase in vesicular stores of NE and 5-HT
130
Fluoxetine are inhibitors of?
CYPD2D
131
Fluvoxamine inhibitor of?
CYPD3A4
132
Citalopram, Escitalopram and Sertraline have what kind of interactions with CYP?
Modest interactions with CYP
133
increase amine release by antagonism of α-2 receptors
Mirtazapine
134
Anti-anxiety and anti-depressant
5-HT2 Receptor Antagonist
135
no effect on 5-HT or NE amine transporters
Bupropion
136
Pharmacologic effects of antidepressants
Amine uptake blockade
Sedation
Muscarinic blockade
Cardiovascular effects
Seizures
137
Sympathomimetic effects in the amine uptake blockade include?
increase NE in nerve endings; inhibit reuptake of NE in nerve endings
138
Chronic use of antidepressants for amine uptake blockade leads to?
Low BP
139
Sedation with the use of antidepressants are common in?
Common in TCA and heterocyclic (mirtazapine) and 5-HT2 blockers (nefazodone and trazodone)
140
Muscarinic blockade occurs in?
Occurs with all TCA esp. amitryptaline and doxepine; also with nefazedone, amoxapine, amprotiline
141
Atropine like effects are minimal with?
SSRI and bupropion
142
Cardiovascular effects are common with? and this causes?
TCA causing hypotension, arrhythmias
143
Cardiotoxicity is caused by?
venlafaxine
144
What lowers convulsion threshold?
TCA and MAOI
145
Overdose of what antidepressants causes seizures?
Maprotiline and SSRI’s
146
T or F: Newer drugs more tolerable side effects
T
147
most useful if with psychomotor retardation, sleep disturbances, poor appetite, wt. loss
TCA
148
for significant anxiety, phobia, hypochondriasis
MAOIs
149
increase suicidal risk
SSRI, SNRI
150
What do TCAs have that SNRIs don't?
antihistamine, alpha blocking, and anticholinergic
effects
151
Antidepressant for Neuropathic pain
Duloxetine, venlafaxine
152
Antidepressant for OCD
Clomipramine and SSRI
153
Antidepressant for Stress incontinence and vasomotor menopausal symptoms
SNRI
154
Antidepressant for for patients withdrawing from nicotine dependence
Bupropion
155
Causes serotonin syndrome
SSRI
156
Serotonin syndrome is characterized by?
interaction of fluoxetine and MAOI
157
Why is fluoxetine not recommended to be used with MAOIs?
Fluoxetine has long half life
158
Serotonin syndrome drugs include?
MAOIs
TCAs
Meperidine
MDMA
Antiseizure drugs
Management drugs
Muscle relaxants
Blockers of 5-HT
159
Causes a dose dependent increase in BP
Venlafaxine
160
Causes weight gain
Mirtazapine and Trazodone
161
Causes seizures and cardiotoxicity
Amoxapine, amrotilline
162
Hypertensive crisis in patients taking MAOIs and high ____ in diet
Tyramine
163
Causes hepatic microsomal enzyme inhibition
SNRI, 5-HT2 antagonists, and heterocyclic drugs
164
Venlafaxine is metabolized where to form?
In liver
Desvenlaxafine
165
Lowest protein binding amongst all antidepressants
Venlafaxine
166
Well absorbed
Half life of 12hrs
Tightly bound to proteins
Duloxetine
167
MOA of Venlafaxine?
Inhibits NE transporters
168
Most SNRIs have a great affinity for SERT or NET?
SERT
169
TCA plasma half life?
8-36hrs
170
MOA is the Potentiation of NTA actions at post synaptic receptors
TCA
171
Antagonism of muscarinic receptors in TCAs are marked with?
Amitryptyline
172
What GCPR is distributed around the cortex?
5-HT2A
173
Weak inhibitor of SERT and NET but potent against 5-HT2A
Nefazodone
174
Selective inhibitor for SERT with little effect on NET
Trazodone
175
Trazodone metabolic which is a potent 5-HT2A antagonist
M-CPP
176
Weak-Moderate presynaptic adrenergic blocking properties
Modest antagonist of H1
Trazodone
177
Resembles amphetamine and has CNS activating structures
Buproprion
178
Biphasic elimination phase of Buproprion
1st - 1hr
2nd - 14hrs
179
New antidepressant with no sexual side effects
Piperazino-azepine group
Mitrazapine
180
Mitrazepine enhances the release of?
5-HT2 and 5-HT3
181
Similar properties with Maprotiline
Rapidly absorbed
Amoxapine
182
Used in Parkinson's
Inhibits MAO-B
Selegiline
183
BDNF affects what parts of the brain?
Hippocampus
Anterior cingulate gyrus
Medial frontal cortex
