Depression/ Mania Drugs For Block III Flashcards
(169 cards)
1
Q
Definition of a:
Receptor-
Neurotransmitter-
Nueromodulator-
A
Receptor: a cellular macromolecule or a macromolecule complex with which a medication interacts to elicit a cellular response
Neurotransmitter: Substance that enables neurons to communicate with each other
Neuromodulator: Any substance that has an effect on neurotransmission
2
Q
What is the current understanding of neurotransmittion
A
Current understanding that the brain has a combination of voltage and chemical transmission
3
Q
What is the pathway of a neurotransmitter from Synthesis to reuptake
A
Synth- realease- Effect/activation of receptor- degradation- reuptake
4
Q
Neurotransmitters action is terminated by what two methods
A
Degradation via enzymes
Reuptake into the presynaptic neuron
5
Q
What is the major NT in the PNS and SNS and what degrades it
A
Acetylcholine:
Major NT in Parasympathetic & Sympathetic systems (activates Nicotinic & Muscarinic receptors and degraded by Acetylcholinesterase)
6
Q
What are the three Amino Acid NTs and what degrades them
A
GABA, Glutamate/aspartate, Glycine/taurine
Degraded by Transaminase
7
Q
What is the effect of GABA stimulation
A
Inhibitory/ Sedative
8
Q
What is the effect of Gluatmamte/ aspartate NTs
A
Excitatory, Stimulating
9
Q
What are the 4 types of amines NTs and what degrades them
A
Dopamine, NE, Seretonin, Histamine
Degraded by Monoamine Oxidase
10
Q
What are the two Neuropeptide NTs and what degrades them
A
Opiods and Techykins
Degraded by peptidases
11
Q
What does amantadine do
A
Increase the release of Dopamine
12
Q
What does long term antagonism or reduction of NT release cause
A
Up-regulation of receptors
13
Q
What does sustained release or slow elimination of NTs cause
A
Down regulation of receptor
14
Q
Dx Criteria for MDD
A
Depression + 5 S/s of SIGECAPS
15
Q
What is SIGECAPS
A
Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor, Suidice
16
Q
What are the gender differences as it relates to depression
A
Females have less serotonin, earlier onset, longer episodes, greater recurrence and more seasonal
More likely to attempt suicide (but less likely to complete the suicide), 2-4 x increase during menopause
17
Q
What are the three main classifications of depression
A
Reactive/ Secondary
Unipolar
Bipolar affective
18
Q
What is the option for refractory depression, depression in therapy, or psychotic depresssion
A
Electro therapy
T.I.D.
19
Q
What do all medications classified as Antidepressants do
A
increase the synaptic concentration of norepinephrine, dopamine, and/or serotonin
Three ways to increase these neurotransmitters:
- Inhibit the reuptake of neurotransmitters
- Block the metabolic degradation
- Increase the release of the neurotransmitters
20
Q
Serotonin is released from what kind of neuron
A
Raphe neurons
21
Q
TCAs, SSRIs, and SNRIs, have what MOA
A
block the reuptake of 5-HT and increase synaptic concentrations
22
Q
How are BZDs used with antidepressants
A
Not classified as an anti-depressant
Used short-term in acute anxiety management while SSRIs are initiated
23
Q
What is the difference between tertiary and secondary amines (TCAs)
A
Tertiary amines:
More potent at blocking reuptake of serotonin > norepinephrine
Include: amitriptyline, clomipramine, doxepin, imipramine
Secondary amines:
More potent in blocking reuptake of norepinephrine > serotonin
Include: nortriptyline, desipramine, and protriptyline
24
Q
TCAs have effect on what Receptors
A
Presynaptic SERT and NET
Postsynaptic A1 blocker
25
What is the MOA of TCAs
Block the reuptake of norepinephrine and serotonin (precursors to SNRI) into the presynaptic neuron which increases the concentrations of monoamines in the synaptic cleft (debated theory)
Also block alpha adrenergic, histamine and muscarinic receptors (anticholinergic side effects)
26
What is the ADE of TCAs
Anticholinergic S/e
27
Are TCAs first line Tx
seldom used as 1st line depression treatment; due to adverse effects and new agents available
28
What can TCAs be used for
Depression
Anxiety Disorders
(NOT 1st LINE!)
Numerous off labeled uses such as:
Treatment for pain syndromes: useful in chronic pain
Migraine prophylaxis
29
What is the Onset of TCAs
2-4 weeks
30
What are the cautions and warnings for TCAs
Most commonly used drug in an overdose
(Avoid in suicidal pts)
Can produce serious, life-threatening cardiac arrhythmias, delirium, coma, seizures, and psychosis
(T.C.A These Cause Arrhythmia’s)
Should not be used in patients with suicidal ideations
Should avoided in patients with cardiovascular conditions, closed angle glaucoma, urinary retention, or severe prostate hypertrophy (Anticholinergic Effects)
31
What are Anticholinergic Fx
Anticholinergic Effects: dry mouth, urinary retention, constipation, blurred vision
Dry mouth is a suggested link to weight gain due to the tendency for patients to drink excessive caloric beverages
The anticholinergic effects will make BPH worse
32
Are TCAs sedating?
Yes they block Histamine
33
Which TCAs cause the most sedation, Anticholinergic efffects, and Alpha blockade
Amitryptyline, Doxepin, Clomipramine
34
What is Doxepin indicated for
Depression and insomnia
35
What is clomipramine approved for
OCD
36
What TCA can be used for childhood bed wetting in chlidren older than 6
Imipramine
37
Which two TCAs specifically mention weight gain
Notriptyline (2kgs) and Amitriptlyine (1.5kgs)
38
What receptors do SSRIs effect
Presynaptic SERT
39
What is the MOA of SSRI
Inhibit serotonin reuptake, without affecting reuptake of norepinephrine or dopamine into the presynaptic neuron
SSRI’s do not significantly effect histamine, muscarinic or other receptors
40
What is the onset of SSRI
3-8 weeks
41
1st line for depression
SSRI
42
1st line for OCD
SSRI
43
1st line for Panic DO
SSRI
44
1st line for social phobia
SSRI
45
1st line for PTSD
SSRI
46
1st line for Premenstral Dysphoric DO
SSRI
47
1st line for GAD
SSRI
48
What is the advantage of SSRI over TCAs in Tx depression
Not as lethal in cases of overdose
Low cost and better pt outcomes
49
Which SSRI has the longest 1/2 life
Fluoxetine
1-3 days for parent drug and active metabolites are 4-16 days
50
What is the 1/2 life of most SSRI
About 1 day, except fluoxetine
51
Which SSRI has the shortest 1/2 life
Fluvoxamine is the shortest with half-life at 15 hours
52
All SSRI interact with CYP 450 except for
Citalopram and escitalopram
53
What are the SSRI that are most activating
Fluoxetine and Sertaline
54
Which SSRI are most sedating
Paroxetine and Fluvoxamine
55
Which SSRI has the worst wt gain
Paroxetine
56
What are the ADE for SSRI
Gastrointestinal: nausea, diarrhea, constipation
CNS: agitation, anxiety, tremor, or panic may be seen in during the early phase of therapy
Sexual Dysfuntion
Serotonin Syndrome
EPS
57
What are the interventions that can be used to combat the sexual dysfunction of SSRIs
Wait-and-see method
Lowering the dose of the SSRI
Switching to bupropion or adding ED medication (i.e. sildenafil)
58
What are the severe ADE of SSRIs
Serotonin Syndrome
Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Especially with elderly
EPS side effects:
Include akathisia, dystonias, and parkinsonian symptoms
Reported with all SSRI’s, but paroxetine has the most reported
59
What is a severe ADE of SSRIs in elderly pts
SIADH
60
What is EPS
Include akathisia, dystonias, and parkinsonian symptoms
61
Which SSRI has the most risk for EPS
Paroxetine
62
How does Seretonin syndrome present
```
Cognitive effects (thinking)
Neuromuscular dysfunction (movements)
Autonomic dysfunction (reflexes, breathing, hr)
```
63
What is the Tx for seretonin syndrome
Withdraw offending agent(s)!
Supportive care:
Anxiety/seizures -benzodiazepines
Hyperthermia- ice, cooling blankets
Cyproheptadine :
1st generation antihistamine, and 5HT1A and 5HT2 antagonist
64
What is the warning with Citalopram
QT prolongation
65
Can SSRIs be used with Aspirin or NSAIDS
No, DDI, increases bleeding
66
What enzyme does fluoxetine inhibit
2D6
67
What is the clinical use of sertraline
PTSD and MDD
68
Why is paroxetine not recommended in children
Increases SI
69
Can paroxetine be used in pregnancy
Cardiac septal defects in 1st trimester exposure (Cat. D/X)
70
What is fluvoxamine clinically approved for
Only OCD
71
What enzyme does fluvoxemine inhibit
2D6
72
What is the does restriction with citalopram because of QT elongation
No more than 40 mg/day
73
What is the clinical use for the SSRI: vortioxetine
MDD
74
Can vortioxetine be dc abruptly
May be stopped abruptly, but headaches and muscle tension was evident in clinical trials
Recommend that the dose be decreased to 10mg/day for week before full discontinuation
75
What are the 4 strong CYP2D6 inhibitors
bupropion, fluoxetine, paroxetine, or quinidine
76
How should vortioxetine be used with enzyme inhibitors and inducers
Strong inhibitor of CYP2D6: reduce Vortioxetine dose by half when given with a strong CYP2D6 inhibitors: bupropion, fluoxetine, paroxetine, or quinidine
Substrate of CYP2D6 and CYP3A4: consider increasing Vortioxetine dose when given with strong CYP inducers: rifampin, carbamazepine, or phenytoin for more than 14 days
77
What receptors do SNRI Fx
Presynaptic SERT and NET
78
What is the MOA of SNRIs
inhibit the reuptake of 5HT and NE, increasing their levels; little activity for alpha adrenergic, cholinergic, or histamine receptor
79
Which SNRIs have been associated with elevated DBP at high doses
Venlafaxine, desvenlafaxine, and duloxetine
80
What is the SE profile for SNRI
Similar profile to SSRIs
```
Common adverse effects:
Nausea
Headache
Somnolence
Dry mouth
Dizziness
Sexual dysfunction
Insomnia
```
81
Should SNRI and MAOIs be used together
No
82
What is the MOA of Venlafaxine
Mechanism of Action: SNRI with dose-related effect on NE
Doses <150mg/day, primarily a serotonin effect
83
At what dose in venlafaxine primarily a seretonin effect
Less than 150 mg/day
84
What is the clinical indication for venlafaxine
Severe or treatment-resistant depression
Generalized anxiety disorder (GAD)
PTSD (1st line agent along with SSRIs)
85
What two drugs can be used as 1st line agents for PTSD
SSRI and venlafaxine
86
What SNRI can be used when SSRIs fail
Venlafaxine
87
How does venlafaxine work at 75 mg/day vs 225 mg/day
Works as an SSRI at doses ~75mg/day; SNRI at >225mg/day.
88
What is Desvenlafaxine
Active metabolite of venlafaxine
89
What is the clinical use for desvenlafaxine
2nd line agent for MDD
90
What is the MAO of Duloxetine
SNRI with dose dependent NE reuptake inhibition
91
What is the clinical use of Duloxetine
Severe or treatment-resistant depression
Generalized anxiety disorder
Diabetic peripheral neuropathy!
Fibromyalgia!
Chronic musculoskeletal pain caused by chronic lower back pain or osteoarthritis pain!
92
Which SNRI really works on chronic and muscular pain
Duloxetine
93
What pts should Duloxetine be avoided in
Should NOT be used in patients with hepatic insufficiency, end-stage renal disease requiring dialysis, or severe renal impairment
94
What vital sign should be monitored with Duloxetine
BP
95
What is the MOA of levomilnacipran
Stronger inhibitor of norepinephrine reuptake than duloxetine (Cymbalta) or venlafaxine (Effexor)
96
What is the clinical use of levomilnacipran
Only for depression
97
What are the ADE of SNRI: levomilnacipran
May cause hyponatremia and increase bleeding risk
Blood pressure elevation and orthostatic hypotension can occur
98
What is the difference with milnaciprin and levomilnacipran
More active isomer of the SNRI milnacipran (Savella)
Milnacipran (Savella) approved for fibromyalgia, not depression
99
When do NDRIs have an effect
On the presynaptic NE reuptake receptor
100
What is the MOA of Bupropion
dopamine and norepinephrine reuptake (at high doses) inhibitor with minimal activity on serotonin
101
What are the clinical uses of Bupropion
MDD
Smoking cessation
Unlabeled: ADHD adjunct
102
What are the ADE of bupropion
Headache, insomnia, irritability, nausea, vomiting, decreased appetite
Weight loss ~4kg
Increased risk of seizures
To reduce seizures: avoid use in susceptible patients;
History of seizure disorders, eating disorders
Associated with less sexual dysfunction than other anti-depressants
103
Bupropion has what contraindication
: patients at risk for seizures
including patients with seizure disorders, history of anorexia or bulimia, or using or withdrawing from medications such as alcohol or benzodiazepines
104
What is the prominent DDI of bupropion
MAO inhibitors
Allow 14 days elapse
105
What are the common affects of SRAs
Antagonists of 5HT2 family of receptors
Antagonists of α1 receptors
Antagonists of Histamine1 (H1) receptors – causes drowsiness
106
What is the MOA of trazadone
modestly inhibit serotonin reuptake (less than SSRIs), antagonist for postsynaptic 5HT2A, H1, and α1 receptors
107
What is the clinical use for Trazodone
Depression in combination with SSRi/ SNRI in patients with sleep DO
108
ADE of Trazadone
Drowsiness and Ortho Hypotension (A1 blockade)
109
What is the MOA of mirtazapine
SRA Inhibits 5HT2A, 5HT3, H1, α1 and α2 receptors, does not have reuptake inhibition effect.
110
What is the clinical use for mirtazapine
MDD, better than TCAs, used with SSRI and SNRI for MDD with sleep DO
111
What are the ADE of mirtazapine
Sedative, low dose sleepiness, high dose insomnia
Reported to have less sexual side effects than the SSRIs
Increased appetite, significant weight gain and hyperlipidemia
Constipation
Dry mouth
Asthenia
112
How is mirtazapine cleared
Renally!! Lower dose if CrCl <30ml/min
113
What is the MOA of Nefazadone
Inhibits 5HT2 family of receptors, α1 receptors, and reuptake of serotonin + norepinephrine
114
What is the clinical use of Nefazadone
Anxious depression, or in SSRI with too much sex dysfuntion
115
What is the black box warning with nefazadone
Risk of liver failure
116
What is the MOA of MAO-I
blocks the enzyme responsible for the break down of norepinephrine, dopamine and serotonin which increases the stores of these transmitters in the neurons
117
What is the clinical use of MAO-I
Atypical depression
(hypersomnia, hyperphagia, and mood reactivity)
Patients refractory to other anti-depressant agents
118
What are MAO-I food interactions
Tyramine
119
What are the ADE of MAO-I
Hypertensive Crises: increased levels of catecholamines, which can be the result of ingestion of tyramine containing foods
Serotonin Syndrome: when levels of 5HT become too high usually as the result of multiple serotonergic agents
Orthostatic hypotension
Peripheral edema
Weight gain
Sexual dysfunction
120
Are MAO-I such as phenelzine and Tranylcypromine 1st line agents
No, considered last line agents
121
What foods should be avoided with MAOIs
avoid use with cheese, wine, beer, sausage, liver and several other items
122
How long should the waiting period be when switching someone to a MAOI
Wait 2 weeks after discontinuing antidepressant before initiating the MAOI
Except Fluoxetine waiting period should be 5-6 weeks
123
What is the MOA and Clincal use of selegiline
MAOI
Clin use: MDD
(High doses require diet modification, Tyramine)
124
Adequate trial of any drug includes:
Adequate trial of any agent includes full therapeutic doses for 2-8 weeks and in some cases for up to 12 weeks
If no response at that point, the drug can be considered a failure
125
What are the strong inhibitors of 2D6
Bupropion
Fluoxetine
Paroxetine
126
What is the strongest inhibitor of 3A4
Nefazadone
127
What two drugs can be used if the pt has sex dysfunction with SSRI, SNRI
Bupropion is not likely to cause sexual dysfunction
Mirtazapine has a lower risk than an SSRI or SNRI to cause sexual dysfunction
128
What drugs can be used if the pt is putting on weight with antidepressants
Bupropion and Fluoxetine are less likely to cause weight gain
129
TCA’s, Mirtazapine, paroxetine, and trazodone- ALL CAUSE what>?
Somnolence
130
Is bupropion activating or sedating
Activating, increases energy
131
What drugs should be used with a pt with antidepressants and needs pain control
Duloxetine (Cymbalta) or venlafaxine in depression plus fibromyalgia or neuropathic pain
Amitriptyline and Imipramine have indication for diabetic neuropathy
132
Which two TCAs are indicated for diabetic neuropathy
Amitriptyline and Imipramine have indication for diabetic neuropathy
133
What SSRI should be used in pts with CV Dz
Sertaline
134
Which SSRI should not be used in obese pts
Paroxetine
135
Which SSRI should be avoided in pts with insomnia
Fluoxetine and sertaline
136
Which SSRi should be avoided in pregnancy
Paroxetine and fluoxetine
137
Which SSRI should be avoided in the elderly
Paroxetine
138
SNRI should not be used in pts with
HTN or Agitation/ Insomina
139
Mirtazapine should not be used in pts with
Obesity or hyperlipidemia
140
Bupropion should not be used in pts with
SZR, HTN, or agitation/ insomina
141
Vortioxetine should not be used in pts with
Nausea or Vomitting
142
What is the tapering method for paroxetine
Decrease by 10 mg q 1-2 weeks
143
What is the tapering method for Sertaline
Decrease by 50 mg q 1-2 weeks
144
What is the tapering method for TCAs
10-25% q 1-2 weeks
145
Do you have to taper Fluoxetine or Bupropion
NO
146
What are the two 2* antipsychotics that are approved for depression augmentation
Only Aripiprazole (Abilify) and Quietiapine (Seroquel) have FDA approval
147
What is the clinical use of lithium
Effective for manic and depressive components
Acts as a mood stabilizer during manic phase
Does not work well in patients who are rapid cyclers (four or more episodes per year)
148
Does lithium work well in pts with cyclothimic mania
NO
149
What is the Therpuic Index for Lithium
Narrow therapeutic index: requires serum blood level monitoring Lithium level (0.8-1.2mEq/L is therapeutic)
150
What are the conditions that effect lithium concentration
Conditions that raise lithium levels: dehydration, fever, vomiting, crash diets and sodium restricted diets can all increase lithium levels
151
What is the standard Lithium W/Up
CBC
Electrolytes
Renal function
Thyroid function tests
Urinalysis
Electrocardiogram (ECG)
Pregnancy test (childbearing age)
152
What are the ADE of lithium
```
Lethargy
Coarse tremor
Confusion
Neurologic and Psychiatric:
Higher plasma levels can cause tremors, convulsions, confusion
```
Seizures
Coma
Cardiac Effects: dysrhythmias can occur at lithium toxicity, which can result in death
153
What effect does lithium have on the thyroid
Decreases thyroid function
154
What renal effects does lithium have
Nephrogenic Diabetes Insipidus/Renal Effects:
Blocks the responsiveness of the renal collecting tubule to vasopressin
Polyuria and polydipsia
155
Can lithium be used in pregnancy
Avoid in 1st trimester in possible
156
How do NSAIDS and lithium interact
NSAIDs will increase Lithium levels due to an enhanced reabsorption of sodium and lithium secondary to inhibition of prostaglandin synthesis
157
What level is severe lithium toxicity
Severe toxicity occurs (level>3mEq/L), hemodialysis may be indicated
158
What is the DOC in manic indications
Valproic ACid and Divaproex sodium
159
What anticonvulsant is the DOC for rapid cycles
Valproic Acid and Divalproex sodium
160
What are the ADE of Valproic Acid and Divalproex sodium
neurotoxicity, sedation, hair loss, teratogenic
| causes spina bifida
161
What is the clin use for carbamazepine
Effective for acute mania and maintenance therapy
Used for long-term management
Can be added to lithium for patients who have not responded to monotherapy
Carbamazepine (Equetro) approved by the FDA for acute manic/mixed episodes
162
What pts should be screened prior to carbamazepine use
Screen for HLA-B*1502 (Asian and Asian Indian) population
Increased risk of severe rash (Steven’s Johnson syndrome)
If positive; carbamazepine should not be used
163
What are the ADE of carbamazepine
Hyponatremia, including SIADH can occur
Rash/Steven’s Johnson Syndrome
Agranulocytosis
164
What is the clin use of lamotrigine
Approved for maintenance therapy
Appears to be effective against the depressed phase of bipolar disorder
165
How should the use of lamotrigine and valproic acid be used together
Valproic acid inhibits the metabolism of lamotrigine and increases the risk of severe skin reactions
Double the dose of lamotrigine if given with carbamazepine
166
What is the primary concern of using lamotrigine
Rash that may present of SJS
Associated with aseptic meningitis in adult and pediatric patients
167
What is the clincal use of BZD in Bipolar DO
ACUTE treatmet,
Useful for insomnia, hyperactivity, and agitation
168
Which two atypical antipsychotics are not approved for use in manic pts
Clozapine and Iloperidone
169
Which 2* antipsychotics are approved for bipolar maintenance monotherapy
Olanzapine (Zyprexa)
Aripiprazole (Abilify)
