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93 Cards in this Set

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During which part of the bipolar cycle do patients make poor life decisions?
Manic
Lifetime prevalence of Bipolar?
1.5%
Which gender is most likely to get Bipolar?
Neither, equal prevalence
Typical onset for bipolar
Around age 20
Men tend to present with _____ Sx originally and Women are more likely to present with ______ Sx originally.
Men: Manic
Women: Depressed
Describe the genetic risk associated with Bipolar Disorder
About 80-90% of patients have a biologic relative witha mood disorder
Describe the monoamine hypothesis in terms of Bipolar disorder
Depression=Deficit of 5-HT,DA,NE
Mania= Excessive catecholamines (DA/NE)
Describe the Sensitization and kindling theories as far as Bipolar Disorder
Basically psychosocial or physical stressors can cause episodes, however, subsequent episodes can occur spontaneously due to increased sensitivity and kindling of the CNS.
Describe the neuroendocrine theories involved in Bipolar Disorder
Excessive thyroid activity can cause mania by increasing beta-adrenergic activity
Describe the Membrane and Cation hypothesis in terms of bipolar disorder
Calcium concentrations inside and outside of cells affect excitability of neuronal firing, this theory implicates that untreated patients have higher levels of calcium intracellularly in platelets and lymphocytes.
Briefly describe the Secondary messenger system theories for Bipolar disorder
Basically, abnormalities in the second messenger systems mess up the release of monoamines. ATPase activity is reduced and therefore a compensatory secondary messenger system
Describe the structural abnormalities that may contribute to bipolar disorder
Lesions in the frontal and temporal lobes are associated with bipolar disorder
Describe the biologic rhythms hypothesis in terms of bipolar disorder
Abnormal circadian rhythms have been reported in bipolar patients (i.e. suppression of melatonin). More mania during the summer. Switching from depression and mania can happen when patient is sleep deprived. Note that a significant life event can induce mania.
Describe what endocrine disorders are associated with mania
Hyperthyroidism
Describe some infections that are associated with mania
AIDs, influenza
Describe neurologic disorders that are associated with mania
Alzheimers, parkinsons
Name 7 agents associated with mania
Antidepressants (least: Buproprion, SSRIs), Pseudoephedrine, DA-augmenting agents, Albuterol, Steroids, Salmeterol, Stimulants
What are some symptoms of mania?
Increased self esteem, not tired, flight of ideas, distracted, directed, activated, dangerous activites, thinking you are god!
What are the 4 diagnostic types of Bipolar Disorder
1.Bipolar I
2.Bipolar II
3.Cyclothymic Disorder
4.Bipolar NOS
Describe Bipolar I
Major depressive episode + manic or mixed episode
Describe Bipolar II
Major depressive episode + Hypomanic episode
Describe Cyclothymic disorder
Chronic fluctuations between subsyndromal depressive and hypomanic episodes (2 years for adults and 1 year for kids/adolescents)
DSM Criteria for Bipolar disorder
1.Distinct period of PERSISTENTLY ELEVATED, EXPANSIVE OR IRRITABLE MOOD lasting 1 week.
2.(3 of the following):
A.Inflated self esteem
B.Decreased need for sleep
C.Pressured speech (flighty)
D.Flight of ideas
E.Easily distracted
F.Increase in goal-directed activity
G.Excessive involvement in pleasurable activities that have painful consequences
3. Symptoms are not a mixed episode
4.Severe enough to cause MARKED INPAIRMENT IN OCCUPATIONAL FUNCTIONING OR IN USUAL SOCIAL ACTIVITIES OR RELATIONSHIPS WITH OTHERS.
Describe hypomania
4 days of abnormal and persistently elevated mood with three of the mania symptoms
Mixed
Criteria for major depressive and manic episode (except for duration) occur nearly every day for 1 week
Describe Rapid Cycling
>4 major depressive, manic, hypomanic or mixed episodes in 12 months
Goals of Treatment for Bipolar Disorder
1.Resolution of bipolar Sx
2.Prevention of future episodes
3.Minimization of ADRs
4.Compliance
5.Patient education
6.Avoidance of stressors that may precipitate episodes
FDA indications for Lithium
Mania associated with bipolar
During which phases of bipolar treatment has lithium been established as effective.
All
In which population of patients would lithium be most effective
Those having PURE mania, fewer prior episodes, hystory of euthymia and family or presonal history of positive response.
Definition of Euthymia
1. Joyfulness; mental peace and tranquility.

2. Moderation of mood, not manic or depressed.
Lithium would be more useful in those patients lacking what medical history?
No neurological impairment, pscyhotic symptoms or history of substance abuse
What is the onset of action for lithium
7-10 days
Lithium MOA
Alters cation transporta cross cell membranes in nerve and muscle cells and influences reuptake of 5-HT and NE
Is lithium highly protein bound?
Not at all
Describe Lithium's distribution in the tissues
HIGHLY distributed in Kidneys (consider GFR), Thyroid (slows T3->T4 conversion) and the bone
How is lithium metabolized?
Its not
Common ADR's associated with Lithium
GI upset
Fatigue
Weakness
Fine hand tremor
Acne
Alopecia
Weight gain
Benign reversible leukcytosis
What RENAL ADR's are associated with Lithium
Diabetes insipidus, polyuria
What endocrine ADR's are associated with Lithium?
Hypothyroidism
What cardiac ADR's are associated with Lithium?
Dysrhythmias
Describe pregnancy implications when using lithium
Category D, Great risk of teratogenicity in the 1st trimester
What general rule of thumb can be used when assessing drug interactions for lithium?
Anything that impacts renal blood flow or modifieds Na stores will have an impact on lithium.
Major Lithium drug interactions
1.ACEi,ARBs (Increase Li)
2.Diuretics (Increase Li)
3.NSAIDs (Increase Li) except ASA
4.NaCl (Decreased Li Levels)
5.Na Depletion (Increase Li)
6.Haloperidol (NeuroTox!)
When should lower doses of Lithium be used?
In elderly and thosed with impaired renal function
Describe lithium dosing
300mg BID-TID titrated upwards depending on response and tolerance. SLOW TITRATION
Describe therapeutics drug monitoring for lithium
1.Initially, draw a level 12 hours after last dose every 4 to 5 days
2.Lithium levels are indicated 5-10 days after dose changes or addition/deletion of drugs affecting lithium clearance or changes in renal function.
What is the desired lithium concentration?
0.6mEq-1.2mEq (1.5 highest)
Describe what labs should be done to monitor lithium?
Baseline: TSH/T4/T3,Renal Fx,CBC,Electrolytes,Weight,EKG and pregancy
Follow-up: Serum Li, Renal/Thyroid,weight and CBC monthly x 3 months then q 6-12m
FDA indcations for valproic
eplipesy, Mania (Bipolar), migraine prophylaxis
Compare the efficacy of Valproic acid vs. Lithium
Found to be as effective as lithium for mania and more effective for fast cyclers
In which patients would Valproic acid be most effective?
Rapid cyclers, mixed mania, and mania due to medical conditions
Describe Valproic acid's antidepressant properties
Poor
Common ADR's for Valproic acid
Gi upset, sedation, weight gain, THROMBOCYTOPENIA
Describe the Black box warning marked on Valproic acid
Hepatotoxicity, Pancreatitis
Which drug can cause Polycystic ovarian syndrome (Bearded lady disease)
Valproic acid
2 Major drug interactions for Valproic acid
Lamotrigine (Kills VPA, Lamotrogine levels go up)
Warfarin - Increase INR
Describe dosing guidelines for VPA
Can give loading dose
Based on response and tolerance
Describe Lab monitoring for VPA
Baseline: Chemistry,LFTs,CBC,weight,pregnancy
Follow-up:[VPA], LFTs,Weight,CBC monthly x 3 months and then q 6 - 12 mo

LIPASE AND AMYLASE SHOULD BE PERIODICALLY CHECKED
Equetro Indications
CBZ: Bipolar disorder
Who is CBZ typically given to?
Those who are refractive to Li or VPA
Onset of action for CBZ
7-10 days
CBZ May be most effective in which patients?
Those having mixed or rapid cycling episodes, neurologic disease and negative family history of mood disorders
PK considerations for CBZ
Major inducer
AUTOINDUCES: Therefore CBZ clearance can DOUBLE with chronic therapy if receiving the same dose
Common ADR's for CBZ
Nystagmus, Ataxia, Blurry vision, drowsiness, dizziness, GI upset, diplopia
Hematological ADR's associated with CBZ
Leukopenia, Thrombocytopenia
BLACKBOX:::Agranulocytosis
BLACKBOX:::Aplastic Anemia
Which major isoenzyme is induced by CBZ?
3A4
Which agents may have decreased levels as a result of CBZ therapy
Anticonvulsants, BZDs, Buproprion, OC's, Antipsychotics, barbiturates and ANTICOAGS
Regarding platelets, at what levels should CBZ be discontinued?
If platelets are below <100,000
OR
WBC <3000
QUICK REVIEW: Li
Tough on Liver/Kidney?
Kidney
QUICK REVIEW: Li
Sedating?
Yes
QUICK REVIEW: Li
Weight Gain?
Yes
QUICK REVIEW: Li
Sexual Dysfunction
Yes
QUICK REVIEW: Li
Monitoring parameters
Li Level
Chem 7
Thyroid
Weight
QUICK REVIEW: VPA
Tough on Kidney/Liver?
LIVER BLACK BOX
QUICK REVIEW: VPA
Sedating?
Yes
QUICK REVIEW: VPA
Weight Gain?
Yes
QUICK REVIEW: VPA
Sexual Dysfunction?
Not really
QUICK REVIEW: VPA
Monitoring parameters
VPA level
CBC
LFT
Weight
QUICK REVIEW: CBZ
Tough on kidney/liver?
Liver
Strong inducer
QUICK REVIEW: CBZ
Sedating?
Yes
QUICK REVIEW: CBZ
Weight gain?
Not really
QUICK REVIEW: CBZ
Sexual dysfunction?
Not really
QUICK REVIEW: CBZ
Monitoring parameters
CBZ level
CBC
LFTs
Chem 7
Major side effect of VPA above all others (not liver)
WEIGHT GAIN
For treatment of Acute Mania, what is the most common treatment?
Mood stabilizer + BZD +/- Antipsychotic
When is an antipsychotic warranted in acute mania?
If patient is hallucinating
3 Mood stabilizers
Li
VPA
CBZ
Why are BZDs not really great agents for the treatment of Mania?
Only cover up the problem
Which AP has been approved for acute mania (and monotherapy)
Arpiprazole
For Bipolar Depression, which SSRI's can be used?
Any but Prozac due to long half-life
What do you do with a patient on an AD that becomes manic?
STOP AD
Describe treatment of Bipolar depression
Maximize Mood stabilizer
Short term AD may be used (Buproprion or SSRI)
Olanzapine/Fluoxetine combo may be a good choice for some.