Psych Neuro Exam 3: Lasilla BPD

Bipolar Subtypes

-Bipolar __

-Bipolar ___

-____

I, II, Cyclothymia

Bipolar I Manic Phase

-characterized by the DSM-5 to be a distinct period of abnormal and persistent expansive or irritable mood lasting __ week or longer

1

Bipolar I Manic Phase

-___ or more of these symptoms also have to be present (inflated self esteem, decreased need for sleep, pressured and increased speech, racing thoughts, agitation, distractibility, risk taking behavior)

3

Bipolar I Manic Phase

-the bipolar disorder impairs the daily ___ of the patient or the patient has the need for ___

functioning, hospitalization

DIGFAST Symptoms of Mania

D = _____

distractibility

DIGFAST Symptoms of Mania

I = _____

insomnia

DIGFAST Symptoms of Mania

G = _____

grandiosity

DIGFAST Symptoms of Mania

F = _____ of ideas/racing thoughts

flight

DIGFAST Symptoms of Mania

A = _____

agitation

DIGFAST Symptoms of Mania

S = _____, pressured

speech

DIGFAST Symptoms of Mania

T = _____ risks excessively

taking

It is difficult to diagnose bipolar disorders because most patients exist in either the ___ or ___ phase of the illness for the majority of the time

depressive, euthymic

Rapid Cycler: ≥___ cycles per year

4

Slow Cycler: <___ cycles per year

4

It is difficult to diagnose bipolar disorders because there is reluctance to seek treatment during the __ phase

manic

It is difficult to diagnose bipolar disorders because there is a high potential for ___ (including Cluster B personality disorders, ADHD, substance induced, schizoaffective disorder, LD/autism, unipolar vs bipolar depression)

misdiagnosis

Neurochemistry of Mania

-increased dopamine in mesolimbic and nigrostriatal pathways

-___ dopamine in TIF and mesocortical pathways

unchanged

Neurochemistry of Mania

-___ outflow of NE pathways

-____ in release of serotonin (leads to agitation, insomnia, euphoria)

increased, increased

Patient Assessment

The ___ of bipolar disorder influences choice of treatment (mania vs depression vs euthymia)

phase

Patient Assessment

-since there is a strong genetic component of bipolar disorder, if patient has family history of disorder, ask what their family's response to ____ was (if family member doing well on med, it is likely they will do well too)

treatment

Patient Assessment

-determine that patient truly has bipolar disorder and not a different ___ (via interview, history, variability in symptom duration, age, symptom severity, etc)

disorder

Drugs which can precipitate manic episodes

1) ___ (may induce a "switch phenomenon")

2) ____ (eg cocaine, amphetamines)

antidepressants, stimulants

Drugs which can precipitate manic episodes

3) ___ or ___

corticosteroids, androgens

Drugs which can precipitate manic episodes

4) ___ medications

5) synthetic ____ (eg JWH-018 and variants)

thyroid, cannabinoids

Therapeutic Targets-stop a car without wrecking it

1) Hit brakes to stop car rapidly (___ pathway)

GABA

Therapeutic Targets-stop a car without wrecking it

2) Disrupting flow of gas, takes more time (interference with ___ channels)

Na+

Therapeutic Targets-stop a car without wrecking it

3) Taking foot off gas, takes the longest (anti-____ ___)

NMDA glutamate

Meds for BPD

1. ___ ____ (lithium, divalproex, carbamazepine, lamotrigine)

2. ____

3. ____ (controversial)

4. ____

mood stabilizers, antipsychotics, antidepressants, benzodiazepines

Meds for BPD

-____ is an adjunctive/common off-label therapy

oxcarbazepine

What are the brand names of Lithium?

Lithium Carbonate, Eskalith

Lithium is the "gold standard" first line treatment for:

-___ mania

-___

-decreased ____/suicidal thoughts

acute, maintenance, suicidality

Lithium

-MOA is to interfere with ___ channels (disrupts flow of gas)

Na+

Lithium

-disadvantage is very ___ therapeutic index and significant ___ ___ profile

narrow, side effect

Lithium Drug Interactions

1. ____ ____ (allow sodium to be reabsorbed, therefore allowing more lithium to be absorbed, causing lithium toxicity)

thiazide diuretics

Lithium Drug Interactions

2. ____ (causes lithium toxicity)

3. ____ (causes lithium toxicity via angiotensin II decrease)

NSAIDs, ACEI

Lithium Drug Interactions

4. ___ intake (increased intake decreases lithium levels)

5. _____ (caffeine, decreases lithium level)

6. ___/____ (theoretical interaction, minor risk of serotonin syndrome)

sodium, methylxanthines, SSRI/SNRI

Lithium Dosage Forms

-lithium carbonate ___ capsules

-lithium carbonate __ tablets

-lithium carbonate ___ capsules

-lithium citrate ___

IR, CR, ER, liquid

Lithium-Test Question

-8meq/5mL of lithium citrate liquid = ____mg lithium carbonate

300

Lithium Acute Phase Dosing

-start patient on ____mg IR BID and adjust by lithium levels

300

Lithium Acute Phase Dosing

-If CrCl < ____ mL/min, dose adjustment needed because lithium is renally excreted

50

Lithium Acute Phase Dosing

-If CrCl < 50 mL/min, consider starting at 300-450mg po ___ (as opposed to usual BID schedule)

QD

Lithium Acute Phase Dosing

-Average dose is 900-1800 mg/day to achieve target drug level of ___-___ mEq/L

0.8-1.2

Lithium Acute Phase Dosing

-steady state is reached in __-__ days

5-7

Lithium Acute Phase Dosing

-even though steady state is reached in 5-7 days, it takes __-__ days for response (so do not adjust dose before this point)

10-14

Lithium Acute Phase Dosing

-since it takes 10-14 days for response to lithium therapy, we can use ___ and/or ____ adjunctively while we are waiting

benzodiazepines, antipsychotics

Lithium Monitor Drug Serum Levels

-we want a trough

-if patient is on BID dosing, draw level before __ dose

-if patient is on QD CR/ER product that is dosed at night, draw level before ____ dose

morning, evening

Lithium Monitor Drug Serum Levels

-we want a trough because "troughs kill"

-if trough is high, that means ___ will be high, and we can delay dose before toxic peak occurs

peak

Lithium Monitor Drug Serum Levels

-monitor serum drug level and creatinine at __ week, __ months, and then every __ months

1, 3, 6

Lithium Monitor Drug Serum Levels

-we monitor serum drug level and creatinine more frequently if patient has ___ sodium changes, changes in ___ intake, changes in ___, or interacting meds prescribed

dietary, caffeine, hydration

Lithium Other Monitoring-Renal Function/Electrolytes

-____

-Cr, CrCl

-__+

-__+

-glucose

BUN, Na, K

-"Lithium loves the ____"

-At the beginning, lithium can cause a brief hyperthyroid phase

-Shortly after, it more commonly leads to hypothyroidism from decreased thyroid hormone release

thyroid

Lithium Other Monitoring-Thyroid Function Test

-free ___

-____

-____

-reverse __

T4, TSH, T3, T3

Lithium Other Monitoring-Parathyroid Hormone

-____

-___

PTH, Ca

Lithium Other Monitoring

-____ (remember there are sodium channels in heart and vasculature)

-____ (category D-risk outweighs benefit)

ECG, pregnancy

Lithium Continuation and Maintenance Treatment

-re-evaluate lithium levels and continue to target optimal __-___mEq/mL

0.8-1.2

Lithium Continuation and Maintenance Treatment

-clinical pearl: target for MDD augmentation is __-__mEq/L

0.4-0.6

Lithium Continuation and Maintenance Treatment

-Lithium exhibits linear kinetics

-A dose change of 300mg translates into a __-__mEq/L change in plasma concentration (if someone has normal renal function)

0.2-0.4

Lithium Continuation and Maintenance Treatment

-need for lower doses in the __ and those with compromised __ function

elderly, renal

Symptoms which respond in first 2 weeks on lithium therapy:

-less pressured ___

-less psychomotor activity

-less ___

-___ patterns begin to normalize

speech, agitation, sleep

Symptoms which respond later on lithium therapy:

-___

-____ processes

-insight and judgement

delusions, though

Goals of Lithium Therapy

1. prevent next ___ episode

2. prevent lithium ____

manic, toxicity

There will be __-___ side effects during the first 14 days of lithium therapy

self-limiting

Lithium Self-limiting Side Effects

-___ discomfort and ___ (most common)

GI, sedation

Lithium Self-limiting Side Effects

-fine hand ___

-diarrhea, polyuria, polydipsia

tremor

Clinical Pearl: Consider ___ daily bedtime dosing with either IR or ER formulation to improve adherence (the patient will then experience side effects such as fine tremor at night and not during the day)

once

If the self-limiting side effects persist after the first 14 days, consider lithium ____

toxicity

Lithium Long Term Side Effects

-____ gain

-abnormalities in ___ panel (hypothyroidism)

-hyperparathyroidism

weight, thyroid

Lithium Toxicity

mild toxicity → serum levels __-__ mEq/L

1.5-2

Lithium Toxicity

mild toxicity → ___ tremor, nausea, vomiting, diarrhea

fine

Lithium Toxicity

moderate toxicity → serum levels __-__ mEq/L

2-2.5

Lithium Toxicity

moderate toxicity → ___ tremor, ataxia, __-wave changes on ECG

coarse, T

Lithium Toxicity

severe toxicity → serum levels >__ mEq/L

2.5

Lithium Toxicity

severe toxicity → ___ (nearly unconscious), seizures, ___ collapse, arrythmias

stupor, CV

Lithium Patient Counseling

-educate patient as to self-limiting vs persistent side effects and __ presentation

toxicity

Lithium Patient Counseling

-maintain ___ status

-maintain consistent __ intake

-maintain diet consistent in ___

fluid, sodium, caffeine

Lithium Patient Counseling

-changes in other medications may require a recheck of lithium levels

-keep appointments for ___ work

-know when to contact physician (cycle into mania or depression, toxicity signs)

blood

Divalproex Sodium

-Divalproex DR and Divalproex ER are NOT ____

interchangeable

Divalproex

-used to treat __ mania and ___ cycling bipolar disorder

-increasing evidence in mania and mixed mania (off label)

acute, rapid

Divalproex

-MOA is to potentiation of post-synaptic ___ receptor (slam on breaks, fastest onset of all mood stabilizers)

GABA

Divalproex

-can cause ___ toxicity

-highly protein-bound to ___ (remember that free drug is therapeutic)

liver, albumin

Divalproex

-only forms approved for BPD are Depakote __ and Depakote ___

-NOT valproic acid (depakene)

DR, ER

Divalproex Dosing

-500mg QD and titrate up to 1000mg/day based on ___, normal ___ function, and serum ___

weight, hepatic, albumin

Divalproex Alternative Dosing

-If a patient presents with acute mania, there may not be time to wait for liver function or albumin labs, so ____-based dosing can be used to start Divalproex treatment right away

weight

Divalproex Alternative Dosing

-weight x 10, then round down

-ONLY can use this alternative dosing for divalproex __

DR

Divalproex DR

-drug is ___/ionized after activation in low pH of stomach

-drug absorbed in small intestine (jejunum)

released

Divalproex ER

-dual layer tablet

-after dissolution, ionization of outer later, inner layer forms a ___ in the small intestine

gel

DR: absorption occurs about __ hours after administration

ER: small immediate release absorption then __-__ extended release

2, 18-24

DR: peak SDL in __ hours

ER: peak SDL in __ hours (so give in morning so sedation peaks at night)

6, 12

DR: 100% absorption

ER: 80% absorption (so must dose __% higher than DR)

20

DR: dosed __-__ times/day

ER: dosed ___ time/day

2-3, 1

Divalproex Therapeutic Effect

-onset of action and steady state achieved in about __ days (fast!)

4

Divalproex Therapeutic Effect

-___mcg/mL of free drug is needed to cross blood brain barrier

50

Divalproex Therapeutic Effect

-50 mcg/mL is needed to cross blood brain barrier, may be lower in presence of ___ serum albumin (because more free drug)

low

Divalproex Target Serum Drug Levels

Acute Phase → ___-___ mcg/mL

100-125

Divalproex Target Serum Drug Levels

Continuation Phase → ___-___ mcg/mL

50-100

low serum albumin = (~___gm/dL or lower)

3.6

If low serum albumin (~3.6gm/dL or lower), request ___ ___ level OR adjust ___ based on conversion table

free VPA, dose

Kinetics of Divalproex

-drug is bound approximately __% to circulating albumin

-creates a circulating reservoir for divalproex

94

Kinetics of Divalproex

-lower albumin = more __ drug = increased risk for ___

free, toxicity

Divalproex Toxicity

-sedation

-____ (confusion, visual hallucinations, rapid onset, caused by increased serum ammonia)

delirium