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144 Cards in this Set
- Front
- Back
What is major depression? |
recurring episodes of dysphoria and negative thinking |
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What is bipoalr disorder? |
Moods swing from depression to mania over time |
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T or F: There are subtypes of major depression and bipolar disorder |
True |
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What does pathological depression resemble? |
An emotional state we have all experienced but differs significantly in intensity and duration (most important) |
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What does pathological depression cause? |
loss of interest in almost everything and inability to experience pleasure |
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What is the loss of interest in almost everything and the inability to experience pleasure called? |
Anhedonia |
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What do most patients with anhedonia mean? |
Hopelessness, sadness, worthlessness, guilt and desperation |
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T or F: Mania often occurs alone |
F, rarely occurs alone |
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What most often accompanies mania? |
It alternates with periods of depression to form bipolar disorder |
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How often does mania often last? |
Days not hours |
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What is the primary symptom of mania? |
Elation |
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What are some of the other symptoms besides elation of mania? |
1. little sleep need 2. unlimited confidence in themselves 3. impulsive decisions |
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What is the overall prevalence of major depressive episode among US adults? |
6.7 (about 7/100) |
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What age group has the highest prevalence of 12-month major depressive disorder? |
18-25 (10.3%) |
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What age group has the second highest prevalence of 12-month major depressive disorder? |
26-49 (7.5%) |
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What age group has the lowest prevalence of 12-month major depressive disorder? |
50+ (4.8%) |
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What race has the highest prevalence of 12-month major depressive episode? |
Mixed race (12.2%) |
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What race has the lowest prevalence of 12-month major depressive episode? |
Asian |
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What is the prevalence of 12-month major depressive episode in females? |
8.5% |
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What is the percentage of males that have had a major depressive disorder of 12-month prevalence? |
4.7% |
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Which gender gets more episodes of major depressive disorder? |
Female |
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Why is it thought that females have a higher prevalence of depressive disorder? |
1. guys dont talk about it 2. guys more likely to commit suicide 3. guys drink more because it is more acceptable for them to deal negative behavior |
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What is the lifetime prevalence of major depressive disorder? |
17% major depression for a long time |
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What percent of the US population has a lifetime prevalence of depression? |
3.9% |
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What percent of the US population has a 12-month prevalence of depression? |
2.6% |
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What percent of US population has a 12-month prevalence classified as severe? |
2.2% |
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Severity: 82.9% of these cases (2.2% of US adult population are classified as what? |
severe |
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What is the average age of onset for major depressive episode? |
25 year old |
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T or F: thoughts of suicide are uncommon with affective disorders |
False, very common |
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What percentage of depressed individuals attempt suicide? |
7-15% |
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What percent of the overall population attempts suicide? |
1-1.5% |
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What percent of people with bipolar disorder have attempted suicide? |
25-50% (most studies 40-50%) |
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Describe bipolar disorder #1 |
1. manic depression 2. periods of fluctuating mania and a swing to depression 3. Primary driver of effective drug treatment is different than bipolar 2 |
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Describe bipolar disorder #2 |
Characterized by predominantly depressive that fluctuates with a milder form of mania called hypomania |
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In bipolar two, which symptom do you treat and how? |
depression; respond better to anti-depressants |
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What are the monoamines? |
Dopamine, catecholamine, serotonin |
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How did the monoamine hypothesis originate? |
With the observation that reserpine induces depression as a side effect |
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What is reserpine primarily used for? |
The treatment of high blood pressure |
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How does reserpine cause depression? |
Prevents packaging or neurotransmitters into vesicles, leaving them in the cytoplasm where monoamine oxidases degrades them |
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What does reserpine do? |
inhibits vesicular uptake and storage, cannot be released, MAO degrades them |
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What is the fate of monoamines when it comes to reserpine like meds? |
stay in the cytosol resulting in less in the cells |
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Bottom line: why is reserpine making people derpessed? |
Took away amines |
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What is the normal function of MAO? |
Function of MAO is to metabolize monoamine transmitters in the presynaptic terminal. |
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What does MAO inhibition do? |
Increases the amount of neurotransmitter available for release |
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What is a big problem with MAO? |
Significant risk of liver toxci |
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Are MAOs widely prescribed for for depression? |
No, used infrequently, only when someone doesn't response to other classes |
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What are Tricyclic antidepresseeants named for? |
Their three ring structure |
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Are TCAs widely used? |
Not |
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How do tricyclic antideprssants act? |
by binding to the presynaptic transporter proteins and inhibiting reuptake of monamines |
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TCAs have the same effects as what drug? |
cocaine |
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What are the monoamines? |
NE, DA, 5-HT |
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TCAs basic structure |
All look like 3 benzene rings |
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What are the side effects of TCAs? |
1. sedation and fatigue 2. small therapeutic 3. potentially dangerous cardiovascular effects |
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What are the potentially dangerous cardiovascular side effects of TCAs? |
1. hypotension (orthstatic, drop in systolic) 2. tachycardia (elevated HR) 3. arrhytmias |
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Can you overdose on TCAs? |
Yes, and commit suicide |
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What are second-generation antidepressants designed for? |
to be more selective and have fewer side-effects |
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How do SSRIs work? |
by blocking the presynaptic re-uptake transporter for 5-HT |
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What was Prozac originally developed for? |
High BP |
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Who makes prozac and what is the story of its approval? |
Eli Lily, tested for high bp but did not work and Eli realized they had increased mood |
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On what do SSRIs have significant influence on? |
1. sensitivity to pain 2. emotionality 3. response to negative consequence or reward |
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What are rats with depleted 5-HT like? |
1. Irritable 2. aggressive 3. overly sensitive to pain 4. altered patterns of eating and satiety |
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What are the antidepressant action of SSRIs related to? |
Increased 5-HT function at some serotonergic receptors |
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What are the side effects of SSRIs? |
1. anxiety 2. restlessness 3. movement disorders 4. muscle rigidity 5. nausea 6. headache 7. insomnia 8. sexual dysfunction 9. motor function 10. Sleep |
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where has low 5-HIAA ben found postmortem? |
In both the brains of suicide victims and in the CSF of depressed patients |
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What is the 5-HT precursor? |
Tryptophan |
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What is 5-HIAA? |
The main metabolite of serotonin |
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T or F: Tryptophan can be used to measure low serotonergic function |
True, it is the precursor |
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T or F: Trytophan is usually high in depressed patients |
False, low |
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Can SSRIs cause physical dependence? |
YES |
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How long do withdrawal symptoms last? |
Several week |
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What are the alleles of the serotonin reuptake transporter? |
two alleles-long and short |
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What does SERT mean? |
serotonin reuptake transporter |
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What percent of people have the short allele? |
10-15% |
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What is the short allele of SERT associated with? |
reduced level and function of the transporter |
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Having the short allele of SERT is a what for depression? |
Risk factor |
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How is the short allele significant in medication? |
Those with it respond better to SSRIs than those who do not have it |
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How do antidepressants increase 5-HT? |
1. by blocking the re-uptake 2. inhibiting MAO |
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What happens at first with anti-depressants? |
the increase in synaptic 5-HT activates autoreceptors to slow firing and reduce synaptic 5-HT |
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An increase in the synaptic cleft translates into what? |
Increase in auto receptors |
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Antidepressants typically take how long? |
2-4 weeks |
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What is the bottom line about the time it takes for for antidepressants to work? |
down regulates the autoreceptor |
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What does long-term administration of antidepressant result in? |
Down-regulation of the autoreceptors and synaptic 5-HT gradually increases |
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Go through the steps of antidepressants on serotenergic cells |
1. Released 2. Binds to autoreceptor 3. shuts down release 4. downregulation 5. now leftover serotonin can activate the postsynaptic cells |
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Where are autoreceptors located? |
Presynaptic terminal |
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Where are serotonin receptors located? |
Post-synaptic membrane |
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What is the basis of serotonin syndrome? |
SSRIs have potentially life threatening effects when combined with other serotenergic agonists or drugs that interfere with metabolism of the SSRIs |
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What are the side-effects of serotonin syndrome? |
1. severe agitation 2. disorientation 3. ataxia 4. muscle spasms 5. fever 6. shivering 7. chills 8. diarrhea 9. elevated BP 10. increased HR |
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What is the serotinin-ne hypothesis of depression? |
There are anatomical and functional interactions between NE neurons originatin in the locus coeruleus and the 5-HT neurons in the raphe nuclei |
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T or F: serotonin and NE systems are capable of modulating the other |
True |
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What does current thinking suggest of therapies for affective disorders? |
Enhancing both NE and 5-HT function is more beneficial than enhancing only one |
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What are examples of dual NE/5-HT modulators? |
Effexor and Cymbalta |
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Even though Cymbalta does affect mood, what do most people report? |
Less aches and pains |
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What is the goal of third-generation antidepressants? |
Speed onset of effectiveness and reduce side effects |
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What stage are third-generation antidepressants currently in? |
Development and testing stages |
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What are the two new approaches to therapies for affective disorders? |
1. CRF receptor antagonism 2. enhancement of cAMP second-messenger system |
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CRF_____ can be used to help treat depression. |
inhibition |
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What does the glucocorticoid hypothesis focus on? |
The stress-related neuro-endocrine abnormalities of depression |
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What do depressed patients have an abnormally high secretion of? |
CRF |
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The hypothalamic CRF neurons are normally controlled by what other areas? |
the amygdala stimulates and the hippocampus has inhibitory control |
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What does an overactive amygdala mean? |
Too much stress |
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What are the stress hormones pathway? |
Hypothalamus, pituatary, ACH, Adrenal |
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What happens to glucocticoid levels when stress is prolonged and intense? |
It remains high, hippocampal neurons are damaged and no longer respond |
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What does damage to the hippocampus include? |
Decreased dendritic branches and spines in the PFC and hippocampus. Formation of new hippocampal cells is inhibited |
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What happens when the hippcampus shrinks? |
Cant stop hypothalamus from releasing CRF |
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What does cell loss in the hippocampus mean? |
Reduced response to cortisol levels and loss of feedback inhibition of the HPA axis |
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What do antidepressant drugs do to CRF levels? |
Reduce them and revers loss of hippocampal dendrites in animal studies |
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What did CRF receptors antagonists that were developed show early promise of? |
antidepressants with minimal sideffects |
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What happened to the CRF receptor antagonists as antidepressants? |
Frequent elevation in liver enzymes and further development was halted |
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Depressed patients have high levels of what? |
CRF |
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What do early life traumas alter? |
the set point for the HPA axis |
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What does the alteration of the set point for the HPA axis do? |
Make it permanently over-responsive and increasing risk for later depression, anxiety, disorders, alchol abuse |
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What do rats subjected to early-life trauma show? |
high stress-induced ACTH and cortisol, increased CRF in brain, permanent increase in CRF gene expression as adults |
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What did antidepressant drug treatment prevent in adult rats? |
CRF increase, and also it reduced fearful behaviors |
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What happened do CRF increase and reduction in fearful behavior in adult rats after they ceased treatment? |
Termination caused the abnormalities to return |
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What does the prevented CRF increase by new antidepressant drugs in adult rats show? |
new direction for antidepressant drug development and that treatment may have to be continued indefinitely |
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What is the neurotrophic hypothesis? |
Low BDNF may be responsible for the loss of dendritic branches and spines in the hippocampus and PFC and for reduced neurogenesis in the hippocampus |
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What is BDNF? |
Brain developed neurotrophic factos |
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What may antidepressants do to BDNF? |
May prevent decrease of BDNF |
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What is the supporting evidence for the neurotrophic hypothesis? |
1. Chronic Stress reduces BDNF in the hippocampus in rats. 2. Chronic but not acute antidepressant treatment increases BDNF in animals and humans 3. Antidepressants prevent stress-induced reduction in BDNF and neuronal atrophy |
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Stress, increase glucocorticoids and decreased BDNF cause what? |
Atrophy and decreased survival and increased vulnerability of hippocampal cells |
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What do antidepressants, increase in NE and 5-HT and BDNF cause? |
Increased survival and growth of hippocampal cells |
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What is the evidence for BDNF in the etiology of depression? |
BDNF is low in the hippocamppus and PFC of depressed patients postmortem BDNF gene polymorphism may be associated with mood disorders Modifying gene expression in mice leads to depressive behaviors |
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What is the most effective medication for patients with bipolar disorder? |
Litium carbonate |
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Does lithium have an effect on healthy individuals |
No |
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What does lithium carbonate do for those with bipolar disorder? |
eliminates or reduces manic episodes without causing depression or producing sensation |
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How effective is lithium carbonate in reducing suicide in bipolar individuals? |
VERY effective |
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Lithium Bromide dramatically does what? |
Increases the time between both depressive epidsodes and manic episodes (particularly manic ones) |
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What action does lithium enhance? |
5-HT actions |
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How does lithium enhance 5-HT actions? |
By elevating brain tryptophan, 5-HT and 5-HIAA and increasing 5-HT release |
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What does lithium do to catecholamine activity? |
Reduces catecholamine activity by enhancing reuptake and reducing release |
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Given that lithium flattens the extremes of emotion in both directions, what is it likely that is modifies? |
Synaptic transmission at points beyond the neurotransmitter receptors, for instance, in second-messenger function |
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What are the side effects of lithium? |
generally mild but may include 1. Increased thirst and urination 2. Impaired concentration and memory 3. Fatigue 4. Tremor 5. Weight gain |
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Is the therapeutic index high or low for lithium? |
Very low; blood levels of lithium must be monitored on a regular basis |
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What are some alternatives to lithium? |
Valproate Carbamazepine |
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What is valproate also called? |
Depakote |
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How does Valproate work? |
An anticonvulsant drug approved for treating acute mania |
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How does Valproate work? |
Enhancing GABA and blocking Na+ channels |
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What is the effectiveness of Valproate similar to? |
Lithium but different side effects |
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T or F: Valporate is safe for women of childbearing age |
False, not good it its limited in this population and is teratogenic |
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What is carbamazepines also called? |
Tegretol |
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What is Carbamazepine primarily? |
Anticonvulsant |
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How does caramazepine work? |
Blocks Na+ channels, Agonists at GABA-A receptors Releases serotonin |
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What seems to work better at first, Carbamazepine or lithium? |
Carbamazepine |
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By what time period does the carbamazepine and lithium seem to balance out? |
14-21 day of treatment |