PHRM845-FINAL EXAM Flashcards

Pharmacotherapy of bipolar disorder

1
Q

What two things must a patient have to be diagnosed with bipolar disorder?

A

Mania and depression

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2
Q

Lifetime prevalence of bipolar disorder

A

2.4%

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3
Q

Clinical factors of bipolar disorder

A

Disease course
-Age at onset (late adolescents/early adulthood)
-Episodic course with episodes lasting a few weeks to several months
-Acceleration of cycle frequency is common as illness progresses
-Depression is the mood pole that is experienced most often in bipolar disorder–can lead to misdiagnosis

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4
Q

Comorbidities of bipolar disorder

A

-Alcohol and substance use is common (50-60%)
-2-3x higher mortality rate than general population
-Anxiety disorders are common comorbidities and can significantly impact remission of mood episodes if left untreated or inadequately treated

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5
Q

What is mania?

A

-Abnormally and persistently elevated, expansive, or irritable mood
-Grandiosity, flight of ideas, distractibility, pressured speech, decreased need for sleep, agitation, excessive involvement in pleasure activities
-Hospitalization is generally required
-Severe episode may involve psychosis
-Change in sleep pattern often initiates episode

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6
Q

What is hypomania?

A

-Less severe form of mania, hospitalization not often required
-Elevated, expansive, or irritable mood symptoms
-Inflated self-esteem, decreased need for sleep, distractibility
-No psychotic features
-Appear like type A (fly around to various types of projects)

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7
Q

What is rapid-cycling?

A

-Characterized by four or more mood episodes in 1 year
-Not based on mood changes in a day

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8
Q

Bipolar I classification

A

At least 1 manic episode, depressive or hypomanic episode may have occurred; manic episodes generally last at least 1 week

**Pt experiences at least 1 manic episode

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9
Q

Bipolar II classification

A

Major depressive and hypomanic episodes; hypomanic episodes generally last at least 4 days

*No manic episodes

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10
Q

Does bipolar mixed with depression matter for classification?

A

NO; just based on if the patient had a manic episode

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11
Q

What is mixed features of bipolar disorder?

A

It is a clinical conundrum that is confusing

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12
Q

What medication works best for mixed features of bipolar disorder?

A

Valproate

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13
Q

Target symptoms of mood for bipolar disorder

A

-Euphoria/elation/happiness
-Depression
-Lability
-Irritability
-Hostility
-Dissatisfaction

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14
Q

Target symptoms of cognitive/perceptual

A

-Flight of ideas
-Racing thoughts
-Grandiosity
-Delusions
-Hallucinations
-Ideas of reference
-Fragmented thoughts

**DOES NOT INCLUDE DISORDERED THINKING

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15
Q

Target symptoms of activity/behavior

A

-Pressured speech
-Impulsivity
-Insomnia
-Aggression/outbursts/violence
-Increased sexual dysfunction
-Panic

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16
Q

Pharmacotherapy overview for bipolar disorder

A

-Mood stabilizers are the foundation of acute and maintenance treatment
-First line: usually lithium or valproic acid (atypical antipsychotics can also be used as first line, as monotherapy, or in combination with lithium or valproic acid)
-Many pts will take polytherapy with mood stabilizers

17
Q

What are the mood stabilizing agents?

A

-Lithium
-Valproic acid
-Carbamazepine
-Oxcarbazepine
-Lamotrigine
-Topiramate

18
Q

What are the antipsychotic agents?

A

Atypical antipsychotics are FDA-approved for acute and/or maintenance bipolar disorder with or without psychosis

19
Q

Lithium use and dosage forms

A

-Good for classic mania and for pts with suicidal ideation
-Decreases number and severity of episodes in bipolar disorder
-Associated with decrease in suicidality—lithium has a narrow therapeutic index, so it can be fatal in OD. Evaluate if the pt has a suicidal plan and if so, if it involved OD via pill ingestion
-It comes in a citrate liquid (IR) and carbonate tablets/capsules (IR or CR)
-Some difference in the lithium content, but use 1:1 conversion!

20
Q

Lithium monitoring and adverse events

A

-Narrow therapeutic index: toxicity is above 1.2-1.5 mEq/L and we must think about renal function
-Toxicities: GI, ataxia, coarse hand tremor, altered mental status, seizure, lethargy, confusion, agitation
-SE: fine hand tremor, hypothyroidism (stopping med will NOT stop this; clear SE of lithium–treat with levothyroxine), polyuria, polydipsia, acne, dry mouth, weight gain, ECG changes
-Teratogenic: Avoid in 1st trimester, use with caution in 2nd and 3rd trimester (distributed based on volume; must increase lithium dose during pregnancy)
~Happens a lot less often than previously thought
~Have preg planning convo
~Corrected by surgery if unplanned

21
Q

Lithium lab monitoring

A

-SCr, BUN (almost entirely renally excreted)
-Urine specific gravity
-Na, K, Ca
-ECG
-Thyroid function test-TSH and T4
-Parathyroid
-CBC with differential
-Weight
-Pregnancy test
**RENALLY CLEARED AND TIED TO SODIUM
**Need pts to be consistent with fluid and sodium intake

22
Q

Lithium drug interactions

A

-Decreased lithium renal clearance which increases lithium levels from ACEi, ARBs, thiazide diuretics, NSAIDs, and dehydration
**Use acetaminophen (tylenol) if needed

-Increased Li renal clearance which decreases Li levels with caffeine, osmotic diuretics, and loop diuretics

-Increased Li excretion (decreases lithium levels) with sodium bicarbonate and high Na intake
-Toxicity related to Na depletion from thiazide diuretics

23
Q

Valproate (valproic acid, divalproex)
-Dosage forms
-Dosing

A

-ER dosage form is ~10-15% less bioavailable than delayed release dosage form
~1:1 conversion, expect lower serum concentration with the ER dosage form (usually not clinically significant)

-Valproic acid syrup (IR) and capsule sprinkle form-higher risk for GI ulcerations (usually esophageal)

-Usual initial dose is 1000 mg given as a nighttime dose or split into 2 divided doses
~Serum levels 80-125 mcg/ml are associated with most efficacy in mania; obtain level at least 96 hours (4 days) after first dose or dose increase

24
Q

Valproic acid adverse effects

A

-Unsafe in ANY trimester of pregnancy–obtain baseline pregnancy test
-PCOS occurs in up to 50% of women who take valproic acid
~Assess for menstrual cycle changes or hirsutism
~May treat with metformin
~Refer to endocrinologist
-GI–anorexia, N/V/D, dyspepsia, ulceration
-Thrombocytopenia, platelet dysfunction
-Teratogenic–neural tube defects, enduring negative effects on IQ of offspring
-Increased appetite (weight gain: 6-8 kg)
-Hyperammonemia

25
Valproate lab monitoring
-Baseline pregnancy test, LFTs, CBC with differential -serum concentration -Serum ammonia-if suspect hyperammonemia (routine ammonia monitoring is not necessary)
26
Valproate drug interactions
-Significant concern with combination use with lamotrigine--increased lamotrigine serum concentrations increase the risk of SJS
27
Carbamazepine
-Considered 2nd or 3rd line -Known teratogen -Induces nearly all CYP450 enzymes -Serum concentration not well correlated to efficacy in bipolar disorder -Associated with thrombocytopenia/hematologic effects
28
Oxcarbazepine
-Considered 2nd or 3rd line -May be used as adjunctive therapy -CYP450 3A4 inducer (NO auto induction) -Associated with hyponatremia, but less hematologic effects compared to carbamazepine
29
Lamotrigine
-1st line tx for DEPRESSIVE sx in bipolar disorder *Not useful for acute treatment or for manic episodes -Slow dose titration due to SJS
30
Topiramate
-Clinically used as adjunctive tx -Limited efficacy as a mood stabilizer in placebo-controlled studies -Slow dose titration to avoid cognitive deficits (dope-amax) -May cause weight loss -Heat intolerance/hypo hidrosis -Metabolic acidosis and kidney stones -Possible teratogen--cardiac structural defects -DRESS warning
31
Antipsychotics in bipolar disorder
**Clinically, it is okay to use them as monotherapy **Think about quetiapine and lurasidone specifically -Atypical antipsychotics (except brexpiprazole, clozapine, iloperidone, and paliperidone) are FDA-approved for acute and/or maintenance tx (manic/mixed episodes) with and without psychosis
32
Antipsychotics in bipolar disorder (clinical pearls)
-Atypical antipsychotics may be used as monotherapy or can be used in combination with other mood stabilizers (usually valproate or lithium) -Antipsychotic polytherapy is not appropriate in most cases for psychiatric illnesses -All monitoring parameters for metabolic syndrome and movement side effects apply when used for bipolar disorder -Can use lithium + antipsychotic, lithium + valproate, or valproate + antipsychotic **Can NOT use 2 antipsychotics together
33
Treatment considerations
-Mood stabilizer tx is long-term and considered to be maintenance tx to reduce time to subsequent mood episodes **Keeps pt from rapid cycling -Tx is limited by tolerability to meds and med adherence -Suicide attempt risk is high in both poles of bipolar disorder--monitor closely and use lithium cautiously **More pts die from bipolar/schizophrenia than depression
34
Combination tx
-Drug regimens in psychiatry is as much an art as a science (may result in difficult regimens) -Combo often designed based on pt response, drug interactions, and adverse effects -Lithium and valproate can be used together and can also be used with an antipsychotic
35
Tx in pregnancy
-Lithium, valproic acid, carbamazepine, and topiramate are known or possible teratogens -Atypical antipsychotics, besides olanzapine and clozapine, are often used in pregnancy because they are thought to have less evidence of teratogenic effect
36
Antidepressants in bipolar disorder
-Depression is experienced most often -Use of antidepressants is linked with a switch to mania ~Questionable efficacy of antidepressants for depression in bipolar disorder ~Need to have maintenance mood stabilizer tx in combo with antidepressant tx -Anxiety disorders are a common comorbidity in bipolar disorder: will use serotonergic antidepressants to tx anxiety