Anxiety & Mood Disorders (pharmacology Flashcards
(147 cards)
1
Q
Benzodiazepines potentiate the ____ receptor
A
GABA
2
Q
Diazepam- effects?
A
- Sedation (little effect on REM sleep)
- Anterograde amnesia
- Anxiolysis
- Ventilatory depression (potentiated by other CNS depressants)
- Anticonvulsant
3
Q
Diazepam- adverse effects?
A
- Tolerance
- Withdrawal syndrome
4
Q
Diazepam- indications?
A
General anxiety disorder
5
Q
Lorazepam- indications?
A
General anxiety disorder
6
Q
Alprazolam- indications?
A
- General anxiety disorder
- Panic disorders
7
Q
Clonazepam- indications?
A
- General anxiety disorder
- Panic disorders
8
Q
Flumazenil- actions?
A
- Inverse agonist @ benzodiazepine receptor
- Short duration
- May cause excessive anxiety
9
Q
Buspirone- actions?
A
- 5-HT1A partial agonist (not a benzo- litte action on dopamine or GABA receptors)
- Lower efficacy than Diazepam (as anxiolytic)
- No sedation, anticonvulsant, or tolerance effects (low abuse potential)
- May be useful for pts who abuse or are at risk of abusing benzodiazepines
10
Q
Buspirone- indications?
A
General anxiety disorder (up to 4 wks, safe up to 1 yr)
11
Q
Fluoxetine- actions?
A
- Selective serotonin reuptake-inhibitor
- Lag time: ~3-4wks
- ↑ 5-HT at presynaptic receptors → ↓ 5-HT synthesis, release
- Downregulation of presynaptic receptors after few weeks
- No sedative, anticholinergic, CV effects
12
Q
Risk of Fluoxetine overdose?
A
Very safe in overdosage
No sedative, anticholinergic, or CV effects
13
Q
Fluoxetine- adverse effects?
A
- Anxiety/Mania, Irritability, Insomnia
- Nausea
- ↓ libido, anorgasmia, erectile dysfunction
- use in children controversial*
however. ..
- Very safe in overdosage
- No sedative, anticholinergic, CV effects
14
Q
Citalopram- type of drug?
A
SSRI
15
Q
Escitalopram- type of drug?
A
SSRI
16
Q
Paroxetine- type of drug?
A
SSRI
17
Q
Sertraline- type of drug?
A
SSRI
18
Q
Fluvoxamine- type of drug?
A
SSRI
19
Q
Serotonin Syndrome- clinical signs?
A
Myoclonus & Tremor Hyperreflexia & Hyperthermia Confusion & sweating Muscle rigidity & Tachycardia Coma & Seizures
20
Q
Antianxiety SSRI’s & SNRI’s- Dependency risk?
A
Minimal risk of dependency
21
Q
Antianxiety SSRI’s & SNRI’s- long- or short-term efficacy?
A
Long-term efficacy
22
Q
SNRI’s- indications & safety?
A
- May be effective in ppl who don’t respond to SSRI’s
- Safer than tricyclics due to CNS selectivity
- More sedating than SSRI’s
23
Q
Venlafaxine- type of drug?
A
SNRI
24
Q
Duloxetine- type of drug?
A
SNRI
25
Mirtazepine- type of drug?
alpha-2-adrenoceptor antagonist
26
Mirtazepine- actions?
- alpha-2-adrenoceptor antagonist
- ↑ release of NE and 5-HT
- Pharmacological effects are
similar to SSNRI’s
27
Tricyclic antidepressants- actions?
↓ NE reuptake
28
Tertiary vs. Secondary Tricyclic antidepressants:
Prototype?
Sedating effects?
Anticholinergic effects?
Tertiary:
- Prototype: Amitriptyline
- Very sedating
- Significant anticholinergic effects
Secondary:
- Prototype: Desipramine
- Less sedating
- Fewer anticholinergic effects
29
Amitriptyline- type of drug / effect?
Tertiary Tricyclic Antidepressant
- ↓ re-uptake of NE & 5HT & has both central and peripheral anticholinergic effects
(TCAs general effect = ↓ NE reuptake)
30
Amitriptyline- effects in "normal" vs. depressed persons?
“Normals”:
- No elevation in mood
- Sedation, dec'd concentration
- Prominent anticholinergic effects (dry mouth & blurred vision)
Depressed persons:
- Improvement in mood (several wks lag)
- Tolerance to sedation develops
- ↑ stage-4 sleep, ↓ REM sleep (facilitates sleep, but not physiologic)
31
Amitriptyline- adverse effects?
- Sedation
- Dry mouth
- Orthostatic hypotension (alpha-adrenergic blockade)
- Mania
- Weight gain
- ↓ seizure threshold (↑ frequency) -- ONLY in persons w/ epilepsy
- Cardiac toxicity
32
Amitriptyline- cardiac effects?
- ↑ heart rate (anticholinergic)
- ↑ conduction time
- T-wave flattening or inversion
- ↓ contractility
- Overdosage may be fatal due to ventricular arrhythmias
- Lidocaine is antiarrhythmic of choice
33
Tricyclic Antidepressants- overdosage?
Common: 3rd leading cause of drug-induced death
- Larger dose = slower absorption
- Fatal dose ~ 1 -2 weeks supply
- Seizures common
34
Imipramine- type of drug?
Tertiary Tricyclic Antidepressant
35
Clomipramine- type of drug?
Tertiary Tricyclic Antidepressant
36
Doxepin- type of drug?
Tertiary Tricyclic Antidepressant
37
Nortriptyline- type of drug?
Secondary Tricyclic Antidepressant
38
Atypical Antidepressants
Trazodone, Nefazodone
- Very sedating
- Few anticholinergic effects
- 5-HT2A antagonism
- ↑ 5-HT release (5-HT1 antagonism)
- Little effect on cardiac conduction
39
Bupropion- type of drug?
↓ NE & DA reuptake
| but not 5HT
40
Bupropion- Side effects compared to other anti-depressants?
- Lowers seizure threshold more than any other antidepressant (epileptics)
Little or no effect on:
- Sedation
- Anticholinergic effects
- Orthostatic Hypotension
- Cardiac effects
41
Bupropion- Seizure effect? Uses other than depression Tx?
- Lowers seizure threshold
| - Also useful in alcohol & nicotine withdrawal
42
What were the first effective antidepressants?
MAO-inhibitors
43
MAO-A vs. MAO-B?
MAO-A = Gut
MAO-B = Brain
(MAO-inhibitors inhibit both)
44
MAO detoxification properties?
MAO important in detoxifying dietary
| amines, e.g. tyramine
45
MAO-inhibitors drug interactions?
Dangerous to use in combo w/ Meperidine
46
Isocarboxazid- type of drug?
MAO-inhibitor
47
Phenelzine- type of drug?
MAO-inhibitor
48
Tranylcypromine- type of drug?
MAO-inhibitor
49
Lithium- effect?
- ↑ NE, DA release
- No effect on 5-HT release
- Also no known physiological function (alkali Group 1 metal)
50
Lithium- distributes where?
To total body water (well absorbed by GI)
51
Lithium: ↓ __?__ → ↑ t½
Na+
52
Lithium- adverse effects?
- Low therapeutic index (2x TD = toxicity)
- Thirst
- Drowsiness
- Weight gain
- T-wave flattening on ECG
```
Toxicity- Mild:
Nausea, vomiting
Abdominal pain, diarrhea
Sedation
Tremor
```
```
Toxicity- Severe:
Hyperreflexia
Cranial nerve signs
Nephrogenic diabetes insipidus
Seizures
Coma
```
53
How is severe lithium intoxication treated?
Dialysis
| however, neurological impairment may be permanent
54
Bipolar Disorder- management?
Acute mania:
- Antipsychotic and/or sedative
- Lag time for lithium effects onset
Chronic bipolar disorder:
- Anticonvulsant (Carbamazepine, Valproic acid, Lamotrigine)
- Lithium
55
Types of meds used for anxiety?
Benzodiazepines, Buspirone, SSRIs, & SNRIs
56
SSRIs- indications?
- Developed as antidepressants
| - Also useful as anxiolytics
57
SNRIs- indications?
- Developed as antidepressants
| - Also useful as anxiolytics
58
When do SSRIs start working?
Usually a lag time of 3-4 wks but can be 7-8 wks before a meaningful therapeutic effect is evident
59
Important SSRI drug interaction?
Most SSRI’s are metabolized by CYP2D6 and most are also inhibitors of this isozyme. This is the source of a particularly important drug interaction with the estrogen antagonist, tamoxifen, that is a prodrug that is converted to its more active form by
CYP2D6.
60
T or F? Up to a fourth or a third of persons with an anxiety disorder will have a
clinical response to the administration of a placebo
True
61
Mirtazapine has a similar effect to what type of drugs?
Serotonin-Norepinephrine Reuptake Inhibitors
(Mirtazepine is an 2-adrenoceptor antagonist and thus increases the release of both norepinephrine and serotonin from nerve terminals)
62
SSRIs approved to treat anxiety disorder in children?
Fluoxetine & Sertraline
63
Bipolar vs. Depression -- which is more common & which is more heritable
Depression- more common
| Bipolar Disorder- more heritable
64
Mania Txs that decrease DA?
Typical antipsychotics- Haloperidol
| Atypical antipsychotics- Risperidone
65
Mania Txs that stabilize mood?
```
Lithium
Valproate
Carbamazepine
Atypical Antipsychotics
Lamotrigine (prophylaxis of bipolar depression)
```
66
4 brain areas most involved in affective neuroscience?
Prefrontal cortex (Goal & appetitive behaviors)
Anterior Cingulate (Emotional Arousal)
Amygdala (Emotional Significance)
Hippocampus (Emotional Learning)
67
_____ Dysfunction Increases Depression Vulnerability. Deep brain stimulation to this area appears able to improve refractory depression.
Subfrontal Cingulate
68
Rats with learned helplessness develop decreased _____
catecholamines
| Consistent with the monoamine depletion hypothesis
69
Genes associated w/ depression: The _____ may be associated with vulnerability to depression
5HT transporter (SERT)
70
______ gene on chromosome 17 associated with vulnerability to depression (though controversial- appears to only increase depression risk with early abuse and only in women)
Short variant of promoter region of SERT
71
Disorders ass'd w/ depression?
```
Hypothyroidism
Cardiac (post-MI)
Pancreatic & other CA
Stroke (L>R)
Alzheimer disease
Traumatic Brain Injury
Parkinson disease
Epilepsy
Diabetes
AIDS/HIV
Chronic Pain
Lyme & inflamm diseases
```
72
______ dysfunction can look like depression
Dorsolateral prefrontal
73
Dorsolateral prefrontal dysfunction Sx?
```
■ Abulic, unmotivated
■ Apathetic (occasional outbursts)
■ Psychomotor slowing
■ Concrete, stimulus bound
■ Perseverative, poor problem solving, disorganized
■ “Pseudodepressed”
```
74
Disorders that can cause mania?
```
Hyperthyroidism
Stroke (R>L)
Traumatic Brain Injury (R>L & orbitofrontal)
Epilepsy
Infection (HIV, neurosyphilis)
Frontotemporal dementia
Hepatic encephalopathy
```
75
______ dysfunction can look like mania
Orbitofrontal
76
Orbitofrontal dysfunction Sx?
```
■ Child-like euphoria (“moria”)
■ Facetious humor (“witzelsucht”)
■ Shallow, labile affect
■ Social disinhibition
■ Impaired judgment, tact, foresight
■ Impulsive, distractible
■ Difficulty maintaining set
■ “Pseudopsychopathic”
```
77
Use ______ first in depression
SSRI SNRI, mirtazapine or bupropion
78
Use SSRI SNRI, mirtazapine or bupropion first in depression
a) If no response, do what?
- If only partial response, do what?
- If no response, do what?
a) verify sufficient dosage & duration (>4 weeks at full dosage)
b) refer for psychotherapy & consider augmentation (non-MAOi antidepressant, T3, LiCO3 or atypical antipsychotic)
c) use different agent or class (above)
79
T or F? All antidepressants can produce sexual dysfunction
Unfortunately, True
80
Avoid ____ in depression Tx, if elevated suicide risk
TCA’s
81
Which responds quicker to depression Tx: Lethargy/anergia or mood?
Lethargy & anergia respond quicker to treatment than mood
82
When to consult psychiatry in depression patients?
If resistant to depression treatment
83
When is neuromodulation used to treat depression?
Neuromodulation is used in refractory depression
| ECT, VNS, DBS, etc.
84
4 neuromodulation Txs: Efficacy? (ECT, VNS, rTMS, DBS)
ECT electroconvulsive therapy- Well documented efficacy
VNS vagal nerve stimulation- FDA approved but only mildly effective
rTMS regional transcranial magnetic stimulation: FDA approved but not reimbursed; time consuming
DBS deep brain stimulation- Investigational but promising
85
ECT- indications & contraindications?
```
Indicated in refractory depression; life-threatening
neurovegetative features (e.g. elderly); catatonia; severe mania
```
Relatively few contraindications
86
Bright Light Therapy is used to treat ______
winter depression
- 10,000 lux for 20-30 minutes in AM
- Full spectrum light
87
Treat acute mania in hospital with ______
3-pronged approach:
- Pharmacologic treatment (Antipsychotic)
- -- Mood stabilizer
- --Anxiolytic
- Reduce stimulation
- Minimize unstructured time
88
3 types of mood stabilizers (evidence-based)?
1. Lithium
2. Anticonvulsants (Carbamazepine, Valproate, Lamotrigine)
3. Atypical antipsychotics
89
Does Gabapentin have evidence as a mood stabilizer?
NO!
90
Lithium notes?
- Requires monitoring of levels, TSH, Renal function
| - Dangerous in OD; But reduces suicidality; 5HT stabilizer
91
Valproate adverse effects?
weight gain; anemia
92
Carbamazepine- adverse effects?
potent CYT inducer; hyponatremia; anemia
93
Lamotrigine- indications?
prophylaxis of bipolar depression only, not mania
94
Atypicaly antipsychotics- indications? Risk?
Risk of metabolic syndrome & tardive dyskinesia
| Best saved for treatment of psychosis
95
Antidepressants carry some risk in ______
Bipolar Disorder
| Always use with mood stabilizer/anti-manic medication
96
Antidepressants share the ability to do what?
potentiate the activity of one or more of the amine neurotransmitters norepinephrine, serotonin, or dopamine
(action is achieved by inhibiting the presynaptic reuptake of the neurotransmitter, increasing its release, or by inhibiting its metabolism)
97
T or F? Psychiatrists treat most depression.
False. Primary physicians treat most depression
98
What types of depression should be referred to psychiatrist?
Refer refractory, bipolar, or atypical patterns to a psychiatrist
99
Etiology of mood disorders vs. vulnerability issues?
Major mood disorders have a neurobiological basis.
| Vulnerability may result from gene-environment interactions.
100
In most cases of depression, a/an _____ will be tried initially because of the significant sedation
that initially accompanies thereapy with a/an _____.
In most cases, an SSRI will be tried initially because of the significant sedation that initially accompanies thereapy with an SNRI.
101
What is the “switch phenomenon” & who is at risk of experiencing it?
Depressed persons with an underlying bipolar disorder given an antidepressant may experience the “switch phenomenon” in which the drug induces a manic episode
102
A potentially exciting method for assessing the ultimate efficacy of a trial of an antidepressant medication?
EEG
(~75% accuracy in predicting ultimate remissions and responses at seven weeks of therapy when applied one week into therapy)
103
Only SSRI approved for depression in children?
Fluoxetine
104
Primary effect of Tricyclic Antidepressants?
Inhibit the reuptake of norepinephrine
105
Prototypical tertiary tricyclic antidepressant (TCA)?
Amitriptyline
106
Untreated overdosage of amitriptyline is often fatal due to what?
Development of malignant arrhythmias
107
Fatal dose of Amitriptyline?
~ 1 – 2 week’s supply
108
If an arrhythmia develops w/ Amitriptyline, what is the anti-arrhythmic drug of choice?
Lidocaine
109
Troubling adverse effect of Amitriptyline that applies to patients who also have Bipolar Disorder?
Some depressed patients will go “beyond” normal and become manic
110
3 tertiary TCAs other than the prototypical Amitriptyline?
Imipramine, Clomipramine, & Doxepin
111
Prototypical secondary TCA?
Desipramine
112
How do the side effects of Desipramine compare w/ those of Amitriptyline?
It causes much less sedation than amitriptyline as well as fewer anticholinergic adverse effects & less weight gain.
Desipramine has similar effects on cardiac conduction and may be lethal in overdosage
113
Similar medication to Desipramine?
Nortriptyline
114
Trazodone & Nefazodone- effects? Adverse effects?
- Only weakly affect NE & 5HT re-uptake
- Antagonize 5-HT2A receptors
- ↑ 5HT release (inhibit presynaptic 5-HT1
receptors)
- Very sedating
- Little anticholinergic activity
- Minimal effects on cardiac conduction
115
MAOIs use today?
In depression patients who fail first-line regimens
116
Why are MAOIs dangerous?
B/c of many drug interactions they participate in, especially fatal ones
117
Dietary restrictions in MAOI patients?
Tyramine reduction
| may experience a hypertensive crisis if ingest tyramine
118
Well-known drug interaction w/ MAOIs that potentiate effects & may cause serotonin syndrome?
Meperidine
119
4 MAOIs to know?
Isocarboxazid, phenelzine, tranylcypromine
MAO-B inhibitor = Selegiline
120
Primary medication for Bipolar Disorder?
Lithium
121
Lithium biochemical effects?
Increases release of NE & DA (but NOT 5HT) from nerve terminals in response to an AP
122
__a__ markedly decreases lithium excretion, and persons with __b__ have a prolonged effect from each dose of lithium
a) Hyponatremia
| b) renal failure
123
Significant lithium toxicity occurs at blood levels about _(#)_x the therapeutic concentration
2 x
124
Therapeutic doses of lithium often cause what?
thirst, weight gain, drowsiness, and T-wave flattening on the ECG
125
Length of time to achieve stable Lithium concentrations?
Several days are required for achieving stable plasma lithium concentrations.
126
Typical long-term management of bipolar disorder?
Mood-stabilizer (Lithium)
&/or
Anticonvulsant (carbamazepine, valproic acid, or lamotrigine)
127
What is needed to make diagnosis of anxiety disorder? (vs. just anxiety)
* some degree of dysfunction
| * symptoms for at least 6 months
128
Anticipatory anxiety?
worse before, better after event
129
In specific phobias, does the person often recognize that the fear is exaggerated or unreasonable?
Yes
130
Generalized Anxiety Disorder
Excessive worry and anxiety more days than not
```
3 or more of:
• Restless, keyed-up, on edge
• Easily fatigued
• Difficulty concentrating/ Mind goes blank
• Irritability
• Muscle tension
• Sleep disturbance
```
131
What is Agoraphobia?
* Anxiety about being in situations from whichescape is difficult
* Avoidance of these situations or markeddistress/ anxiety about being in these situations
* Often occurs with panic attacks but notnecessarily
132
Medications w/ anxiolytics target what 3 sets of neurotransmitters?
- GABA (GAD)
- Cortisol and Norepinephrine (PTSD)
- Serotonin (Panic, OCD, probably plays a role in all forms of anxiety)
133
Adverse effect of using extinction as behavioral method?
Escalation of provoking behavior
Ex: child turns on sink for attention
- --> you ignore it
- --> child floods bathroom
134
Benzodiazepines:
Target?
Advantage?
Problems?
```
Target = GABA
Advantage = effective in aborting anxiety
Problems =
• Not useful in prophylaxis
• Tolerance, addiction
• Toxicity in overdose esp with alcohol
```
135
Clomipramine: Useful in _____
OCD & Social Anxiety Disorder
136
SSRI/SNRI: Advantage? Disadvantage?
Advantage = non addictive, effective in broad range of disorders, lower toxiciy in overdose
Disadvantage = can take 4-12 weeks for effect
137
Tx: Debilitating anticipatory/ performance anxiety
Beta-blockers
138
Tx: Panic Disorder
SSRI
| Benzo as adjunct
139
Tx: PTSD
Treatment tends to be symptomatic
140
Tx: Social Anxiety Disorder
SSRI
| Clomipramine
141
Tx: OCD
SSRI
| Clomipramine
142
Tx: Generalized Anxiety (GAD)
SSRI
SNRI
Buspirone
143
What part/characteristic of the Type A personality is associated w/ an increased risk of cardiac disease?
Hostility
| not competitiveness, so guy w/ road rage has increased risk but Mai Lan's husband racing other sailboat does not
144
T or F? Depression increases risk of cardiac disease.
True
145
T or F? Super-competitivenes increases risk of cardiac disease.
False
| hostility & depression do, though
146
What are the "anxiolytics"?
Benzodiazepines & Buspirone
147
What are the "mood stabilizers"?
Lithium
Carbamazepine, Valproate, & Lamotrigine
Atypical antipsychotics (Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprasidone, Aripriprazole)
