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Bipolar
UMSOPPY3 Bipolar Disorder
191
Pharmacology
Graduate
04/09/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
What are the mainstays of treatment for acute mania and prophylaxis for recurrent manic and depressive episodes?
Definition
Lithium and Valproate
Term
What are alternative or adjunctive treatments for bipolar disorder?
Definition

Anticonvulsants

(lamotrigine, carbamazepine, oxcarbazepine)

 

Atypical antipsychotics

(aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone)

Term
In which mood subtypes are anticonvulsants more effective than lithium?
Definition
mixed states and rapid cycline
Term
Which drugs are more effective for recurrent bipolar depression?
Definition
lamotrigine and lithium
Term
Adjunctive agents include:
Definition

antidepressants

additional mood stabilizers

antipsychotics

benzodiazepines

Term
How does bipolar disorder differ from recurrent major depression or unipolar depression?
Definition
A manic, hypomanic, or mixed episode occurs during the course of the illness
Term
What is the difference between bipolar I and bipolar II?
Definition

Bipolar I - one or more manic or mixed episode

lifetime prevalence is 0.4-1.6%

 

Bipolar II - recurrent major depressive episodes with hypomanic episodes

lifetime prevalence is ~0.5%

Term

Is bipolar I more common in men or women?

 

Is bipolar II more common in men or women?

Definition

men = women

 

women>men

Term

What % of pt with bipolar disorder have a relative with a mood disorder (bp, major depress, cyclothymia, dysthymia)?

 

What is the lifetime risk of developing a mood disorder or bpd if a first-degree relative has bpd?

Definition

80-90%

 

15-35% for mood disorder

 

5-10% for bpd

Term
Where are the genes that likely contribute to bpd susceptibility located?
Definition
X chromosome
Term
What nongenetic factors may play a role in the etiology of BPD?
Definition

1. perinatal insult

2. head trauma

3. environmental factors

4. psychosocial or physical stressors

5. nutritional factors

6. neurotransmitter/neuroendocrine/hormonal theories

7. monoamine hypothesis

8. dysregulation of amino acid neurotransmitters

9. cholinergic hypothesis

10. secondary messenger system dysregulation

11. hypothalamic-pituitary-thyroid axis dysregulation

12. membrane and cation theories

13. sensitization and kindling theories

 

Term
What are possible environmental factors?
Definition

1. desynchronization of circadian or seasonal rhythms

2. changes in the sleep-wake cycle or light-dark cycle

 

Term
What are nutritional factors that may contribute to etiology of bpd?
Definition

1. deficiency of essential amino acid precursors that can lead to dysregulation of NT activity (L-tryptophan deficiency causes a decrease in 5-HT and melatonin synth and activity)

 

2. deficiency in essential fatty acids (omega-3-fatty acids) leading to dysregulation of NT

Term
The neurotransmitter/neuroendocrine/hormonal theories involve dysregulation between excitatory and inhibitory NT systems. Which NT are excitatory and which are inhibitory?
Definition

Excitatory: NE, DA, glutamate, aspartate

 

Inhibitory: 5-HT, GABA

Term

According to the monoamine hypothesis:

 

1. an excess of these catecholamines cause mania?

 

2. a deficit of these NT cause depression?

 

 

Definition

1. NE, DA (so treat with DA antag or a2-agonists)

 

2. NE, DA, 5-HT (so treat with 5-HT inh, NE/DA inh, and MAOIs)

Term
A deficiency of GABA or excessive glutamate activity can cause increased DA and NE activity. What agents increase GABA or decrease glutamate activity are are used to treat mania and for mood stabilization?
Definition
benzodiazepines, lamotrigine, lithium, valproic acid
Term

According to the cholinergic hypothesis:

 

1. (increased/decreased) acetylcholine can increase the risk of a manic episode

 

2. (increased/decreased) acetylcholine levels can increase the risk for a depressive episode

 

3. What are the treatment strategies that go along with this hypothesis? 

Definition

1. decreased = manic

 

2. increased = depressive

 

3. Mania -

agents that increased ACh activity: cholinesterase inhibitors 

   Depressive Episode -

agents that decrease ACh activity:

anticholinergics

 

 

 

Term
What are the three main components of "secondary messenger system dysregulation"?
Definition

1. abnormal G protein functioning

 

2. abnormal cyclic adenosine monophosphate and phosphoinositide secondary messenger system activity

 

3. abnormal protein kinase C activity and signaling pathways

Term

Hypothyroidism can precipitate depression and can be a risk factor for what? 

 

When is thyroid supplementation useful in pts?

 

Definition

rapid cycling

 

when treatment for rapid cycling is refractory or as augmentation to antidepressants in unipolar depression

Term

According to the membrane and cation theories:

 

1. (Hypo/Hyper)calcemia is associated with anxiety, irritability, mania, psychosis, and delirium

 

2. (Hypo/Hyper)calcemia is associated with depression, stupor, and coma. 

 

3. Ca concentrations may affect the excitability of neuronal firing and the synthesis and release of what 3 NT? 

Definition

Hypo

 

Hyper

 

NE, DA, 5-HT

Term
__________ is an antagonist of the catecholamine system and contributes to teh interaction between phosphatidylinositol and phosphatidylcholine secondary messenger systems.
Definition
Acetylcholine
Term
What are the 4 main categories of medical conditions that induce mania?
Definition

1. CNS disorders 

brain tumor, stroke, subdural hematoma, MS, lupus, seizures, Huntington's

2. Infections

encephalitis, neurosyphilis, sepsis, HIV

3. Electrolyte or Metabolic abnormalities

Ca or Na flux, hyper or hypoglycemia

4. Endocrine or hormonal dysregulation

Addison's, Cushing's, hyper or hypothy, menstrual, pregnancy, perimenopausal

Term
What are some medications or drugs that can induce mania?
Definition

Alcohol intoxication

Drug withdrawals

Antidepressants

DA-augmenting agents (CNS stim, amphetamines)

Hallucinogens

Marijuana

NE-augmenting agents (A2antag, Bag, SNRI)

Steroids

Thyroid preparations

Xanthines (caffeine, theophylline)

OTC weight loss and decongestants

Herbals (St.John's Wort)

Term
What are the 4 subtypes of BPD?
Definition

1. bipolar I

2. bipolar II

3. cyclothymic disorder

4. bipolar disorder not otherwise specified

Term
What are the 4 classifications of mood states?
Definition

1. major depressive

2. manic

3. hypomanic

4. mixed

Term
What is the medical term used for normal mood?
Definition
euthymia
Term
Which type of BPD is characterized by episodes of chronic fluctuations between subsyndromal depressive and hypomanic episodes (2 years for adults and 1 year for children and adolescents)?
Definition
Cyclothymic disorder
Term
Which type of BPD is characterized by a major depressive episode(s) and hypomanic episode(s)?
Definition
Bipolar Type 2
Term
Which type of BPD is characterized by manic episode(s) with or without major depressive or mixed episode(s)?
Definition
Bipolar Type 1
Term
Do depressive episodes occur more in T1 or T2?
Definition
T2
Term
What are the atypical depressive features that increase a pts suicide risk?
Definition

1. mood lability

2. hypersomnia

3. low energy

4. psychomotor retardation

5. cognitive impairment

6. anhedonia

7. decreased sexual activity

8. slowed speech

9. carb craving

10. weight gain

Term

1. To diagnose mania how long do symptoms need to be present?

 

2. What are the common symptoms of mania?

 

Definition

1. 1 week with impairment in functioning

 

2. grandiosity, decreased need for sleep or food, pressured speech, flight of ideas (racing thoughts), distractibility, increased activity, poor judgment, and involvement in pleasurable activities with potentially negative consequences

Term
How is a hypomanic episode different from a manic episode?
Definition

1. less severe

2. does not cause marked impairment in social or occupational functioning

3. no delusions or hallucinations

Term

What is a mixed episode?

 

In what population are they more common?

 

How does a mixed episode affect the suicide rate? prognosis? 

Definition

A mixed episode is the simultaneous occurence of manic and depressive symptoms

 

More common in younger patients, more common in women

 

higher suicide rate and a poorer prognosis

Term

When is BPD usually diagnosed?

 

What is the avg. age of onset for a first manic episode?

 

Which type of episode typically presents first in females? males?

Definition

15-30 years old

 

21

 

major depressive episode in females

manic episode in males

 

 

Term

More than __ mood episodes per year = rapid cycling

 

Frequent and severe ____ episodes are the most common hallmark of rapid cycling.

 

What factors contribute to rapid cyclining?

Definition

4

 

depression

 

alcohol, stimulants, antidepressants, sleep deprevation, hypothyroidism, seasonal changes

Term
Early onset bipolar disorder presents similarly to ADHD with extreme irritability or rages before what age?
Definition
7 years old
Term
Fluctuations of hormones and NT during the ____ phase of the menstrual cycle, postpartum period, and during perimenopause can precipitate mood changes and increase cycling.
Definition
luteal
Term

How does BPD affect mortality rate?

 

What % of BPD pt attempt to commit suicide?

 

Are suicide attempts more likely with BP1 or BP2?

Definition

Increased: 2.3x higher

 

50% attempt

 

BP2

Term
What is the best predictor for level of functioning during a person's lifetime?
Definition

adherence to medical treatment

 

50% of pt DC meds because of SE

Term

How long must symptoms be present to be diagnosed as:

1. Major Depressive?

2. Manic?

3. Hypomanic?

4. Mixed?

5. Rapid Cycling? 

Definition

1. >2 weeks

2. >1 week

3. at least 4 days

4. nearly every day for at least 1-week

5. >4 major depressive or manic episodes in 12 months

Term

Diagnostic criteria for a major depressive episode includes

 

>2wk period of depressed mood or loss of interest or pleasure in nl activities associated with at least 5 of the following:

Definition

1. depressed, sad mood (adults) irritable (children)

2. decreased interest and pleasure in nl activities

3. decreased appetite, weight loss

4. insomnia or hypersomnia

5. psychomotor retardation or agitation

6. decreased energy or fatigue

7. feelings of guilt or worthlessness

8. impaired concentration and decision making

9. suicidal thoughts or attempts

Term

Diagnostic criteria for a manic episode includes

 

>1 week period of abnormal and persistent elevated mood (expansive or irritable), associated with at least 3 of the following (or 4 if irritable):

Definition

1. inflated self-esteem (grandiosity)

2. decreased need for sleep

3. increased talking (pressure of speech)

4. racing thoughts (FOI)

5. distractible (poor attention)

6. increased activity (social, work, sexual) or increased motor activity or agitation

7. excessive involvement in activities that are pleasurable but have a high risk for serious consequences

Term

How often should a patient be seen who is:

1. severely ill

2. less ill but symptomatic

3. starting or switching meds

4. continuation phase

Definition

1. q week

2. q2 weeks

3. q2 weeks

4. qmonth for 3 months then q2-3m

Term
How long should a patient be on a mood stabilizer?
Definition
for life
Term

What drugs have A+ ratings as monotherapy for acute mania or mixed states?

 

A+ as adjunctive?

 

 

Definition

Monotherapy:

1. Lithium

2. Divalproex

3. Aripiprazole

4. Olanzapine

5. Risperidone

6. Quetiapine

7. Ziprasidone

 

Adjunctive:

1. Olanzapine

2. Risperidone

3. Quetiapine

 

Term
Which drugs have A ratings for acute mania or mixed states?
Definition

1. Carbamazepine

2. Clozapine - monotherapy for treatment-resistant pts

3. Haloperidol - monotherapy or adjunctive

 

Term
Which drug has a class B rating for rapid cycling?
Definition
Lamotrigine
Term
Which anticonvulsants have an X rating for use in acute manic or mixed states?
Definition

Gabapentin - X for monotherapy and adjunctive

Tiagabine - for monotherapy

Term
Which drugs have an A or A+ rating for use in acute bipolar depression?
Definition

A+: Quetiapine

 

A: Lithium + Lamotrigine

 

Term
Which drugs have a B rating for use in acute bipolar depression?
Definition

1. Carbamazepine

2. Olanzapine - adjunctive with fluoxetine

3. Risperidone - adjunctive

Term
Which drugs have an A+ or A rating for use in continuation or maintenance therapy?
Definition

A+:

1. Lithium carbonate

2. Lamotrigine (Lamictal)

3. Olanzapine (Zyprexa)

 

A: Divalproex (Depakote)

Term

What are the efficacy ratings for lithium carbonate in:

1. acute mania or mixed states

2. acute bipolar depression

3. continuation or maintenance therapy

Definition

1. A+

2. A

3. A+

Term

What are the efficacy ratings for olanzapine in:

1. acute mania or mixed states

2. acute bipolar depression

3. continuation or maintenance therapy

Definition

1. A+ monotherapy or adjunctive

2. B adjunctive with fluoxetine

3. A+

Term
Which anticonvulsant has the best efficacy rating in acute bipolar depression?
Definition

Lamotrigine - A

 

Carbamazepine - B

Term

What are the efficacy ratings for quetiapine in:

1. acute mania or mixed state

2. acute bipolar depression

3. continuation or maintenance

Definition

1. A+ monotherapy or adjunctive

2. A+

3. D

Term
Which drugs are FDA approved for the treatment of acute mania in bipolar disorder?
Definition

1. lithium

2. valproate (or divalproex sodium) (Depakote)

3. aripiprazole (Abilify)

4. olanzapine (Zyprexa)

5. quetiapine (Seroquel)

6. risperidone (Risperdal)

7. ziprasidone (Geodon)

Term
Which drugs are approved for the maintenance treatment of bipolar disorder?
Definition

1. Lithium

2. Olanzapine (Zyprexa)

3. Lamotrigine (Lamictal)

 

Term
Which drug is the only antipsychotic that is FDA approved for bipolar depression?
Definition
Quetiapine (Seroquel)
Term
What is the drug of choice for bipolar disorder with euphoric mania?
Definition
lithium
Term
Which mood stabilizer has better efficacy for mixed states, irritable/dysphoric mania, and rapid cycling?
Definition
valproate
Term
What 3 things should treatment plans be based on?
Definition

1. patient-specific characteristics

2. comorbid psychiatric and medical conditions

3. avoidance of drug interactions and adverse effects

Term

What drugs are recommended for short-term adjunctive treatment of agitation or insomnia if needed?

 

Which is preferred for catatonia?

Definition

benzodiazepines:

lorazepam (Ativan) or

clonazepam (Klonopin)

 

lorazepam (Ativan)

Term
During mania, as a first line treatment which 2-3 drugs should be used in combo?
Definition

1. Lithium or Valproate PLUS

2. benzodiazepine (lorazepam or clonazepam) PLUS

3. atypical antipsychotic if psychosis is present

Term

When is valproate preferred over lithium?

 

Which drugs are preferred for bipolar depression?

Definition

mixed episodes and rapid cycling

 

lithium and lamotrigine are preferred over valproate for depression

Term
Lithium is approved for use in adults and children over what age?
Definition
12 years and older
Term
What monitoring is required to minimize adverse effects of lithium therapy?
Definition

1. renal function

2. thyroid function

3. blood level monitoring

Term
Lamotrigine can cause a severe dermatologic rash when combined with what drug commonly used in BPD?
Definition
valproate
Term
Which antidepressants have a high risk of causing discontinuation syndrome?
Definition

paroxetine (Paxil)

venlafaxine (Effexor)

 

Term
Which drug classes have more adverse effects and a higher risk of causing antidepressant induced mania?
Definition
MAOIs and TCAs
Term
Which SSRIs inhibit liver metabolism and have potential ddis?
Definition

fluoxetine (Prozac)

fluvoxamine (Luvox)

nefazodone (Serzone)

paroxetine (Paxil)

Term
What are the adverse effects associated with atypical antipsychotics?
Definition

extrapyramidal reactions

sedation

emotional blunting

sexual dysfunction

metabolic syndrome

orthostatic hypotension

obesity

T2DM

hyperlipidemia

hyperprolactinemia

cardiac disease

tardive dyskinesia

Term
Which 2 high potency benzodiazepines can be used as an alternative or in combination with antipsychotics in pts with mania, agitation, anxiety, panic, and insomnia, or in pts that can't take mood stabilizers?
Definition

clonazepam

lorazepam

Term
What are some ADE of benzodiazepines?
Definition

1. CNS depression

2. sedation

3. cognitive and motor impairment

4. dependence

5. withdrawal reactions

Term
When can you withdraw antidepressants?
Definition
2-6 months after remission
Term

Although they are rarely used, calcium channel blockers inactivate voltage-sensitive calcium channels, thus inhibiting NT synthesis and release and neuronal signal transmission. 

 

Which nondihydropyridine may have mood-stabilizing properties?

 

Which dihydropyridine?

Definition

Verapamil (Isoptin)

 

Nimodipine (Nimotop)

Term

What are the ADEs associated with CCBs?

 

When can they be used?

Definition

bradycardia and hypotension

 

preferred over lithium or anticonvulsants during pregnancy and breast feeding

 

nimodipine can be more effective than verapamil for rapid-cycling bc it has anticonvulsant properties, is highly lipid soluble, and can penetrate the brain

Term

Are gabapentin and topiramate effective for acute mania?

 

When is topiramate sometimes used?

 

Levetiracetam and zonisamide may have efficacy in what 2 situations?

Definition

probably not

 

as an add on weight-reduction med (but no evidence)

 

mania and for treatment-refractory rapid cycling

Term
Which of the newer anticonvulsants has little support for safety and efficacy as a mood stabilizer and has caused seizures in patients with bipolar disorder?
Definition
Tiagabine (Gabitril)
Term

What are the risks associated with lithium use during the first trimester of pregnancy?

 

Should you breast feed on lithium?

Definition

1.Epstein's anomaly (1:1000-2000)

2."floppy" infant syndrome (low Apgar score, lethargy, hypotonia, bradycardia, cyanosis, shallow respiration, and poor sucking)

3.hypothyroidism

4.nontoxic goiters

 

discouraged

Term
What are the risks of anticonvulsant use during pregnancy?
Definition

1. neural tube defects - 1st trimester

(carbamazepine 0.5-1%, valproate 5-9%)

valproate - spina bifida

2. craniofacial abnormalities

3. developmental delays

4. microcephaly

 

 

Term

How can you reduce the risk of neural tube defects while taking an anticonvusant like valproate?

 

Can you breast feed while taking valproate?

Definition

folate

 

Yes, valproic acid is excreted in low concentrations

Term
What are the features of catatonia?
Definition
mutism, motor excitement, stereotypic movements, waxy flexibility, negativism, echopraxia, echolalia
Term

What drugs are used to treat catatonia?

 

 

Definition
benzos - particularly lorazepam
Term

Why should you minimize the use of antipsychotics in catatonia?

 

What is the preferred treatment in this population?

Definition

Increased risk of neuroleptic malignant syndrome

 

ECT

Term

MOA:

Typical Antipsychotics

Atypical Antipsychotics

Definition

block DA2 receptors

 

block DA2 and 5-HT2A receptors

Term
Which antipsychotics are available in depot formuations?
Definition

haloperidol decanoate

fluphenazine decanoate

risperidone LA injection

Term
What is the only antipsychotic that is FDA approved for maintenance therapy in bipolar disorder?
Definition
Olanzapine (Zyprexa)
Term
Which antipsychotic has not demonstrated efficacy in acute mania and has actually been associated with inducing mania or hypomania?
Definition
ziprasidone (Geodon)
Term
When is carbamazepine used in bipolar disorder?
Definition

not first line

 

reserved for lithium-refractory patients, rapid cyclers, or mixed states

Term

What is carbamazepine's ddi with antidepressants, anticonvulsants, and antipsychotics?

 

What drugs increase carbamazepine levels?

Definition

it increases the hepatic metabolism and dosage increases may be necessary

 

calcium channel blockers (verapamil and diltiazem)

 

Term

What carbamazepine serum level is associated with ataxia, choreiform movements, diplopia, nystagmus, cardiac conduction changes, seizures, and coma?

 

Which hepatic enzymes are induced?

 

What should be done for carbamazepine toxicity?

Definition

15mcg/mL

 

3A4 (mainly), 1A2, 2C9/10 and 2D6

 

gastric lavage, hemoprerfusion, symptomatic treatment - for carbamazepine (Tegretol) toxicity

 

Term

What is carbamazepine's active metabolite?

 

What 3A4 inhibitors can lead to toxicity?

 

What is the interaction between valproate and carbamazepine?

 

What is the potential risk of combining carbamazepine with clozapine?

Definition

10,11-epoxide metabolite

 

cimetidine, diltiazem, erythromycin, fluoxetin, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefazodone, propoyphene, verapamil

 

Valproate displaces carbamazepine from protein binding sites and increases free levels, reduce the carbamazepine dose

 

possibility of bone marrow suppression

Term
What is the desired serum concentration of carbamazepine?
Definition

6-10mcg/mL 

12-14mcg/mL in some treatment resistant pts

Term
What is the MOA of lamotrigine?
Definition

blocks voltage-sensitive sodium channels

modulates or decreases glutamate and aspartate release

and has antikindling properties

Term
Which drug is most effective for prevention of bipolar depression?
Definition
lamotrigine
Term
What are the ADEs of lamotrigine?
Definition

HA, nausea, dizziness, ataxia, diplopia, drowsiness, tremor, rash, pruritis

 

~10% developed maculopapular rash - DC

 

SJS- greatest risk with coadmin of valproate (Valproate decreases the clearance of lamotrigine)

 

DC if diffuse, involves mucosal membranes, with fever or sore throat

Term

Lithium kinetics:

A?

D?

M?

E?

Definition

Absorption - rapidly

Distribution - widely, no protein binding

Metabolism - no metabolism

Excretion - unchanged in urine

 

it is a monovalent cation

Term
What is the goal serum concentration of lithium?
Definition
0.8-1mEq/L - fewer relapses
Term

What are the risks of using lithium with CCBs?

 

Lithium with ECT?

Definition

neurotoxicity

severe bradycardia with verapamil and diltiazem

 

 

acute neurotoxicity and delerium, WD lithium at least 2 days before and resume 2-3 days after the last treatment

Term
What is the BBW for lithium?
Definition

Toxicity (tremor, n/v, diarrhea, drowsiness, muscular weakness)

 

can occur within therapeutic range

Term
Severe lithium intoxication occurs when serum concentrations are higher than _______ and present with 3 key symptoms.
Definition

2mEq/L

 

1. gastrointestinal (v, diarrhea, incontinence)

2. coordination (fine to coarse hand tremor, unstable gait, slurred speech, twitching)

3. cognition (poor concentration, drowsiness, disorientation, apathy, coma)

Term

Lithium DDIs:

1. drugs that elevate lithium concentrations

2. increase neurotoxicity risk

3. enhance renal elimination

 

Definition

1. thiazides, NSAIDs, COX-2I, ACEI, NaCl-restricted diets

2. carbamazepine, diltiazem, losartan, methyldopa, metronidazole, phenytoin, and verapamil

3. caffeine and theophylline

Term
What happens to lithium's clearance rate during pregnancy?
Definition
it is increased by 50-100%
Term

What concentration is recommended for bipolar prophylaxis in the elderly?

 

Acute mania concentrations?

Definition

0.4-0.6mEq/L

 

1-1.5mEq/L

Term
What drug blocks voltage sensitive Na channels, modulates voltage-activated Ca currents, and increases K clearance?
Definition
Oxcarbazepine (Trileptal)
Term
What is the difference between carbamazepine and oxcarbazepine?
Definition

1. Oxcarbazepine is the 10-keto analog of carbamazepine

2. milder ADE

3. no autoinduction of liver enzymes (3A4)

4. potentially fewer drug interactions (controversial)

Term
What are the ADE associated with oxcarbazepine (Trileptal)?
Definition

dose-related:

dizziness, sedation, HA, ataxia, fatigue, vertigo, abnl vision, diplopia, n/v, abp

 

possibly higher rates of hyponatremia

Term
What are the DDI with Oxcarbazepine?
Definition

2C19 inhibitor

3A3/4 inducer

 

induces metabolism of oral contraceptives

Term

What should you do to alleviate the following frequent dose-related ADE with valproate:

1. GI complaints

2. Tremors

3. Sedation

Definition

1. with food, switch to divalproex sodium ER, adding a H2antag like famotidine or ranitidine

2. dose reduction or addition of a BB

3. give total daily dose at bedtime

Term
What are the most serious ADEs associated with Valproate?
Definition

1. Thrombocytopenia

2. fatal necrotizing hepatitis in children with epilepsy receiving multiple antiepileptics (idosyncratic, not dose-related)

3. life-threatening hemorrhagic pancreatitis

Term

What is the maximum recommended dose of valproate?

 

Which valproate formulation has a higher BA? How do you adjust the dose to compensate?

Definition

60mg/kg/day

 

the immediate release has a higher BA by ~15%, if using the XR you will need slightly higher doses

Term

What is the goal trough after the first week of therapy on valproate for acute mania?

 

What do most use for the therapeutic range?

Definition

>45mcg/mL

 

50-125mcg/mL taken 12h after last dose

 

Term

What are the 4 rating scales used in bipolar disorder?

 

What are some recommended QOL scales?

Definition

1. Young Mania Rating Scale

2. Brief Bipolar Disorder Symptoms Scale

3. Hamilton Rating Scale for Depression

4. Montgomery-Asberg Depression Rating Scale

 

Short Form (SF)-36

Psychological General Well Being Scale

Term
What are the 2 different lithium salts and their brand names?
Definition

Lithium carbonate:

Eskalith - 300mg capsule

Eskalith CR - 450 mg ER tab

Lithobid - 300mg ER tab

 

Lithium citrate:

Cibalith-S - 8mEq/5mL 

Term

What is the therapeutic trough of serum lithium concentration:

1. during acute episodes

2. as maintenance therapy

Definition

1.) 1-1.5mEq/L

2.) 0.6-1.2mEq/L

Term
What are the 7 proposed MOAs of lithium?
Definition

1. nomalizes or inh 2nd messenger systems

2. dec. 5-HT reuptake and increases synaptic sensitivity

3. inh synthesis of DA, decreases B receptors and inh DA2 and B receptor supersensitivity

4. Enhances GABAergic activity and nl GABA levels

5. reduces glutaminergic activity (increases glutamate)

6. Decreases Ca transport into cells, interferes with Ca-Na active transport, increases renal tubular reabsorption of Ca and increases serum Ca and parathyroid concentrations

7. Increases choline in RBCs and potentiates the cholinergic 2nd messenger system

Term

What are the brands for divalproex sodium?

 

What serum concentration should divalproex be titrated to?

 

What is divalproex sodium's MOA?

Definition

Depakote - 125, 250, 500mg EC, DR t; 125mg sprinkle cap

Depakote ER - 250, 500mg EC, ER tab

 

50-125mcg/mL

 

1.increases GABA levels in plasma and CNS, inh GABA catabolism, increases synth and release, can prevent reuptake, enhances action of GABA at GABAa receptor

2.normalizes Na and Ca channels

3. reduces intracellular inositol and protein kinase C isoenzymes

4. can modulate gene expression

5. antikindling properties can decrease in rapid cycling and mixed states

Term

How is valproic acid or valproate available commercially? brands?

 

 

Definition

Depakene 250mg capsule (valproic acid)

Depakene 250mg/5mL syrup (valproate sodium)

 

 

Term

What is the brand name for lamotrigine?

 

MOA?

Definition

Lamictal 25,100,150,200mg tablets; 2,5,25mg CT

 

1. blocks voltage-sensitive Na and Ca channels

2. modulates or decreases presynaptic aspartate and glutamate release

3. antikindling properties

Term
What are the brands and formulations of carbamazepine?
Definition

Tegretol, Epitol 200mg tablet

Tegretol 100mg CT, 100mg/5mL suspension

Tegretol-XR 100,200,400mg ER tab

Carbatrol 200,300mg ER cap

Equetro 100,200,300mg ER cap

Term
What is carbamazepine's MOA?
Definition

1. blocks voltage-sensitive Na channels

2. stimulates the release of ADH and decreases Na serum concentrations

3. blocks Ca influx through NMDA glutamate receptor and decreases Ca serum concentrations

4. Modulates presynaptic aspartate and glutamate release

5. Antikindling properties may decrease rapid cycling and mixed states

Term

How is oxcarbazepine available?

 

MOA?

Definition

Trileptal 150,300,600mg t; 300mg/5mL susp

 

Oxcarbazepine and it's active monohydroxy metabolite increase K conductance and modulate the activity of high-voltage activated Ca channels and block Na channels

Term

Benzodiazepine MOA?

 

Which are used in BPD? Availability?

Definition

binds to BZD site and augments action of GABAa by increasing the frequency of Cl channel opening (causing hyperpolarization - a less excitable state) and inh neuronal firing

 

Clonazepam (Klonopin) 0.5,1,2mg t - 0.5-20mg/day 

Lorazepam (Ativan) 0.5,1,2mg t;     2-40mg/day

2mg/mL sol;

2mg/mL + 4mg/mL inj

Term
Which atypical antipsychotics are approved for bipolar disorder?
Definition

Aripiprazole (Abilify) 5,10,15,20,30mg t

Olanzapine (Zyprexa) 2.5,5,7.5,10,15,20mg t

(Zyprexa Zydis) 5,10,15,20mg ODT

Quetiapine (Seroquel) 25,50, (1/2/3)00 t

Risperidone (Risperdal) 0.25,0.5,1,2,3,4mg t

1mg/mL solution

(Risperdal M-Tab) 0.5,1,2,3,4mg 

Ziprasidone (Geodon) 20,40,60,80mg cap

Term
What is the MOA for atypical antipsychotics?
Definition
antagonisize postsynaptic DA2 receptors and block 5-HT2a receptors that increase presynaptic release of DA = lowering the risk of EPS and prolactin release; receptor blockade varies by agent: DA, 5-HT2A-2C, A1-ad, muscarinic, histamine1
Term

What CCB are used as third-line agents in combination with other drugs (carbamazepine, valproate, antipsychotics)?

 

MOA?

Definition

Nimodipine (Nimotop) 30mg capsule - 30-120mg/day

Verapamil (Verelan) 120,180,240,360mg cap -80-480/day

(Calan, Isoptin) 40,80,120mg film-coated t

120,180,240 mg ER t

 

Blocks Ca influx through L-type Ca channels

Alters Ca-Na exchange

Decreases 5-HT, DA, and endorphin activity

Term
Which drugs require hematologic tests (CBC with diff and platelets) at baseline and at 6-12months?
Definition

1. Carbamazepine: DC- plt<100th/mm3; WBC<3th/mm3

2. Lithium 

3. Valproate: DC if plt<100th/mm3 or prolonged bleeding time

Term
Which drugs require metabolic tests (fasting glucose, serum lipids, weight) at baseline and at 6-12months?
Definition

1. Atypical antipsychotics (increased app w weight gain (initial low or normal BMI), rapid or signif gain during early therapy, hyperlipidemia, diabetes)

2. Lithium 

3. Valproate 

Term
Which drugs require liver function tests (ALT, AST, ALP, LD, bilirubin) at baseline at at 6-12months?
Definition

Carbamazepine -DC if liver dysfunction

Valproate

Term
Which drugs should have renal function tests (serum creatinine, BUN, urinalysis, urine osmolality, sp gravity) done at baseline? at 6-12months?
Definition

Carbamazepine + Lithium

Lithium (q2-3m during first 6 then q6-12; if impaired monitor 24-h urine volume and creatinine q3m; if urine volume>3L/day, monitor urinalysis, osmolal, and spgrav q3months)

Term
Which drugs require thyroid function tests (T3, T4, T4 uptake, TSH) at baseline at at 6-12months?
Definition
Lithium - 1-2x during first 6m then q6-12; monitor for hypothy, if supp req, monitor and adj q1-2m until nl then q3-6m
Term
Which drugs require serum sodium monitoring at baseline and again at 6-12 months?
Definition

Lithium

Carbamazepine

Oxcarbazepine

 

Term
Which drugs require dermatologic monitoring (rashes, hair thinning, alopecia) at baseline and at 3-6months?
Definition

Carbamazepine

Lamotrigine - serious dermatologic rxn, SJS, within 2-3mo

Lithium - alopecia

Valproate

Term
Which drug can interfere with some pregnancy tests?
Definition
Carbamazepine (Tegretol)
Term
With this therapy, you should obtain a baseline EKG for pt >40yo or if preexisting cardiac disease (benign, reversible T-wave dep can occur).
Definition
Lithium
Term
Which drug is not recommended during the first trimester of pregnancy due to the risk of neural tube defects?
Definition

Valproate

 

 

Term
Which types of episodes are briefer and end more abruptly that other episodes?
Definition
Manic more so than depressive
Term
What is the avg length of manic episodes that are untreated?
Definition
4-13months
Term

Which drug was recently approved for maintenance treatment?

 

Efficacy?

 

 

Definition

Aripiprazole (Abilify)

 

Showed efficacy in preventing relapse into mania (did not show efficacy at preventing depression)

 

Duration - no systemic data to support use beyond 6 weeks

 

 

Term

Which drug is now FDA approved for maintenance therapy of BPD when given in combination with lithium or divalproex?

 

Efficacy?

Definition

Quetiapine

 

showed efficacy for preventing manic and depressive relapse

Term

Which ADE is more frequently associated with oxcarbazepine than carbamazepine?

A. Ataxia

B. N/V

C. SJS

D. Hyponatremia

Definition
D. Hyponatremia
Term

Which of the following lab tests is needed before initiating therapy with valproic acid?

A. K level

B. LFT

C. Thyroid FT

D. Mg level

Definition
B LFT
Term

Antidepressants can be used when treating a patient with BPD who is currently:

A. depressed and taking a mood stabilizer

B. not depressed but hx of severe depression before each manic episode

C. hypomanic but hx of severe depression

D. Manic but hx of severe depression after manic episode

E. A+B

F. All of the above

Definition
A. depressed on a mood stabilizer
Term

Antipsychotics could be used in a pt displaying which of the following symptoms:

A. Mania with psychotic features

B. Mania without psychotic features

C. Depression with psychotic features

D. A and B

E. All of the above

Definition
E. All of the above
Term

A diagnosis of BPD comes only after a pt has a:

 

A. manic episode

B. hypomanic episode

C. depressed episode

D. A or B

E. All of the above

Definition
D. manic or hypomanic episode
Term

Which medication is FDA approved as monotherapy or adjunctive therapy for BPD maintenance?

A. olanzapine

B. quetiapine

C. risperidone

D. ziprasidone

E. A and B

Definition

E. Olanzapine (Zyprexa) - mono or adjunctive

+ Quetiapine (Seroquel) - adjunctive with lithium or valproate

Term
Hyperprolactinemia and the amenorrhea-galactorrhea syndrome are ADE associated with which drug class?
Definition
antipsychotics - especially those that strongly antagonize DA receptors in the tuberoinfundibular tract
Term

Which statement concerning the use of lithium in the treatment of bipolar affective disorder is accurate?

A. excessive NaCl intake enhances the toxicity

B. it aleviates the manic phase within 12h

C. dosage may need to be decreased in pts on thiazides

D. it doesn't cross the placental barrier and is quite safe in pregnancy

E. elimination rate is equivalent to that of creatinine

Definition

C. Correct

 

*high urinary levels of Na inh renal tubular reabsorption of lithium = decreased plasma levels

*lithium clearance is decreased by distal tubule diuretics (thiazides) because natriuresis stimulates a reflex increase in the proximal tubule reabsorption of Li and Na

*any drug that can cross the BBB can cross the PB. teratogenic risk is low, but use during prego may contribute to low Apgar score in neonate; Ebstein's anomaly - tricuspid

*elimination rate of lithium is equivalent to 1/5th that of creatinine

 

Term

A 30-year-old male is on drug therapy for a psychiatric problem. He complains that he feels "flat" and that he gets confused at times. He has been gaining weight and has lost his sex drive. As he moves his hands, you notice a slight tremor. He tells you that since he has been on medication, he is always thirsty and frequently has to urinate. The drug he is most likely to be taking is:

A. carbamazepin           D. risperidone

B. haloperidol               E. valproic acid

C. lithium

Definition

C. lithium:

confusion, mood changes, decreased libido, weight gain are all symptoms that may be unrelated to drug admin; on the other hand, psychiatric drugs are often responsible for such symptoms. Tremor and symptoms of nephrogenic diabetes insipidus are characteristic adverse effects of lithium that may occur at blood levels within the therapeutic range

Term

Which of the following drugs is established to be both effective and safe to use in a pregnant patient suffering from bipolar disorder?

A. carbamazepine

B. chlorpromazine

C. lithium

D. olanzapine

E. valproic acid

Definition

D. olanzapine;

carbamazepine and valproic acid are effective in BPD but CI in prego because of effects on fetal development. although the potential for dysmorphogenesis due to lithiumm is probably low, the most conservative approach would be to treat the pt with olanzapine. chlorpromazine has no proven efficacy in BPD

Term

The effective treatment of a bipolar pt has necessitated doses of lithium that result in plasma levels of 1.4-1.6mEq/L. Lately he has begun to suffer from increased motor activity, aphasia, mental confusion, and social withdrawal. The best course of action would be to:

 

A. add amitriptyline to the drug regimen

B. continue lithium and add haloperidol

C. DC lithium and start valproic acid

D. DC lithium and start clozapine

E. increase the dose of lithium

Definition

C. DC lithium and start valproic acid;

 

these are symptoms of lithium toxicity. it is appropriate to try an alternative drug (olanzapine, carbamazepine, valproic acid) Clozapine as a single agent has minimal efficacy in BPD.

Term

A young pt treated with an antipsychotic for a few weeks becomes easily fatigued and experiences periodic fevers. Petechiae are apparent on PE, and lab studies revel leukopenia and thrombocytopenia. If a diagnosis is made that the patient is suffering from drug-induced agranulocytosis, he is most likely being treated with:

 

A. aripiprazole

B. clozapine

C. haloperidol

D. olanzapine

E. risperidone

Definition

B. clozapine; 

 

 

Term

Within days of starting haloperidol treatment, a young male developed generalized muscle rigidity and a high temp. In the ER he was incoherent, with increased HR, hypotension, and diaphoresis. Labs indicated acidosis, leukocytosis, and increased creatine kinase. What is the most likely reason for his symptoms?

 

A. agranulocytosis

B. bacterial inf

C. NMS

D. spastic retrocollis

E. TD

Definition

C. Neuroleptic Malignant Syndrome (NMS);

 

result of an extremely rapid block of dopamine receptors in pt who are highly sensitive to EPS of antipsychotics. Management involves fever control, muscle relaxants (dantrolene or diazepam) and possibly admin of dopamine receptor ag (bromocriptine). 

Term

Which of the following drugs has a high affinity for 5HT2 receptors in the brain, does not cause EPS or hematotoxicity, and is reported to increase the significant QT prolongation?

 

A. chlorpromazine

B. clozapine

C. fluphenazine

D. olanzapine

E. ziprasidone

Definition

E. ziprasidone (Geodon)

 

the newer antipsychotics have greater affinity for 5HT2 than DA receptors. Clozapine is hematotoxic. Ziprasidone carries a greater risk of QT prolongation than olanzapine.

Term
Which carbamazepine formulation is the only one FDA approved for bipolar disorder?
Definition
Equetro ER 100, 200, 300mg capsules
Term

How do you reduce polyuria when taking lithium?

 

What is a treatment available to control the lithium-associated tremor?

Definition

change to once daily dosing

 

bb- propranolol 10mg po TID

Term

Which comes first, polyuria or polydepsia?

 

Nephrogenic diabetes insipidus is diagnosed with a urine output >__ L/day

 

Treatment?

Definition

Polyuria

 

3L/day

 

diuretic: loop, thiazides, triamterene

Term
What are the complications with lithium therapy and pregnancy?
Definition

1. Ebstien's anomaly in ~0.1% (1-8x increase)

2. increased neonatal goiter

3. "floppy baby syndrome" - hypotonia, low Apgar score, lethargy, bradycardia, cyanosis, premature delivery, thyroid abnormalities

4. lithium clearance is increased 50-100% during prego

Term

What is the serum lithium level for acute toxicity?

 

maintenance toxicity?

Definition

Acute >6-8mEq/L

Maintenance >4mEq/L

Term

Divalproex peak = 3-5h

Valproic acid peal = 1-4h

 

metabolism?

 

ddi?

 

 

Definition

CYP2C9, 2C19, UGT

 

inh 2C9 + UGT

Term

Valproate ADEs:

 

BBW?

Definition

alopecia, tremor, ataxia, pancreatitis, TCP, hepatotox, hyperammonemia, POS, insulin resis, hyperandrogenism, bone demineralization

 

Hepatotoxicity: fatal; occurs within first 6 months of therapy

 

Pancreatitis: abp, n/v, anorexia

Term
_______ probability from valproate therapy increases in females >110mg/mL and in males >135mg/mL
Definition
Thrombocytopenia
Term
What is a major risk of pregnancy in valproate therapy?
Definition

neural tube defects 5-9%

use folic acid supplementation in women of child-bearing age

Term
Carbamazepine metabolism?
Definition

CYP3A4 substrate

metabolized by autoinduction 

 

Induces CYP3A4, 1A2, 2C9, 2D6 (may decrease levels of BC)

 

 

Term

Carbamazepine ADEs:

 

BBW:

Definition

hyponatremia, thrombocytopenia, leukopenia, agranulocytosis, hepatotoxicity, diplopia, dry mouth, blurry vision, constipation, SJS 5-10%, confusion, arrhythmias, alopecia, lupus-like symptoms

 

aplastic anemia, agranulocytosis (monitor blood levels q2weeks for first 2 months then q3 months)

S/S: oral ulcers, sore throat, easy bruising, bleeding, fever

Term

What are the risks of carbamazepine and pregnancy?

Definition
1. Congenital malformations (spina bifida, craniofacial defects, developmental delays) 0.5-1%
Term

What is the maximum daily dose of oxcarbazepine?

 

What is the MOA?

Definition

2400mg/day

 

10-keto analog of carbamazepine, blocks voltage-sensitive Na channels, modulates voltage-activated Ca currents, and increases K conductance

Term

What is the active metabolite of oxcarbazepine?

 

Inh? Induces?

Definition

10-monohydroxy-carbazepine

 

Inh: 2C19

Inducer: 3A4 (induced metabolism of OC)

 

Term
Oxcarbazepine ADEs?
Definition
sedation, vertigo, n/v, hyponatremia (worse than carbamazepine)
Term

Lamotrigine

 

MOA?

Definition

Lamictal

 

may stabilize neuronal membranes by acting on voltage-sensitive sodium channels; decrease release of presynaptic glutamate and asparte

Term

What are the ADE of lamotrigine?

 

Toxicity?

Definition

TEN, SJS?, 10% have some rash; ataxia, blurred vision, sedation

 

Rash >> with valproate+lamotrigine

 

Tox: stupor, coma, death

Term

What are the ddi of lamotrigine?

 

Aseptic meningitis?

Definition

Lamotrigine increases the serum concentration of valproic acid.

 

Lamotrigine decreases the serum concentration of cabazepine, phenytoin, and phenobarbital

 

 

Term
Lamotrigine use in pregnancy?
Definition

1. possible increase in rate of major congenital malformations

2. increased risk of cleft-lip, cleft-palate

3. greater risks at doses >200mg

Term
Which bipolar drugs must be dispensed with a medguide?
Definition

Clozaril (clozapine) - agranulocytosis

 

Zyprexa Relprevv (olanzapine extended-release injectable suspension) - post-inj delirium/sedation

Term

Symbyax

1. Dose?

2. Indications?

3. CI?

4. Warnings/Precautions?

Definition

olanzapine (zyprexa) + fluoxetine (paxil)

1. capsule

2. Depressive episodes associated with BP1, treatment resistant depression (in MDD)

3. no use with MAOI or within 12d of DC, wait 5 weeks to start MAOI, pimozide or thioridazine - QT prolongation, do not use thioridazine within 5 weeks of DC symbyax

4. worsening/suicide risk, elderly with dementia, NMS, hyperglycemia, hyperlipidemia, weight gain, SS and NMS-like reactions, allergic reaction/rash, activation of mania/hypomania, TD, orthostatic hypo, leukopenia, neutropenia, agranulocytosis, seizures, abnormal bleeding, hyponatremia (SIADH), potential for cog and motor impairment, hyperprolactinemia, long elimination half-life of fluoxetine, lab test (FBG, lipids)

 

Term
What are the dosages available for SYMBYAX?
Definition

Olanzapine/Fluoxetine:

3/25

6/25

6/50

12/25

12/50

Term

Symbyax metabolism?

 

What factors affect metabolism?

 

Definition

Fluoxetine - metabolized by 2D6

Olanzapine - metabolized by 1A2, 2D6

 

smoking status, gender, and age

 

Term
Which atypical antipsychotics are indicated for BP maintenance?
Definition

Mono:

Aripiprazole

Olanzapine

 

Adj:

Quetiapine 

Ziprasidone 

 

 

Term
Which atypical antipsychotics are indicated for the treatment of acute depression in BPD?
Definition

Quetiapine 

Olanzapine (adjunctive with fluoxetine)

 

Term
Which atypical antipsychotics are indicated for acute mania or mixed episodes?
Definition

aripiprazole (Abilify)

asenapine (Saphris)

olanzapine (Zyprexa)

ziprasidone (Geodon)

risperidone (Risperdal)

quetiapine (Seroquel)

Term

Which atypical antipsychotics:

1. is available as SL

2. is available as ODT

3. inj for acute agitation

4. long acting or extended release inj

Definition

1. asenapine (Saphris)

2. aripiprazole, olanzapine, risperidone

3. aripiprazole, olanzapine, ziprasidone*

4. paliperidone, risperidone

 

*indicated for acute agitation with schizo not BPD

Term

1. Which atypicals have the worst metabolic profiles?

2. Which has no QT-prolongation?

3. Which has the least EPS?

4. Most EPS?

5. Most hyperprolactinemia (sexual dysfunction, gynecomastia, irregular periods)?

6. no CYP3A4 metabolism?

7. Most sedation? 

8. least sedation?

Definition

1. olanzapine and clozapine

2. olanzapine

3. iloperidone and quetiapine

4. paliperidone and risperidone

5. paliperidone and risperidone

6. risperidone and olanzapine

7. clozapine

8. aripiprazole, iloperidone, paliperidone, risperidone, ziprasidone 

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