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Flashcards in Drugs to Treat Bipolar Disorder Deck (53):
1

Lithium Clinical Use

First-line treatment
Acute mania, bipolar depression, maintenance treatment
Reduces risk of suicide (BP I, BP II, major depression)

2

How long does it take for Lithium to reach full therapeutic effect?

2-3 weeks

3

Lithium MOA

Unclear
-2nd messenger enzymes
-effects neurotransmitters and release
-effects on electrolytes and ion transport (similar to Na)

4

Lithium protein binding

NONE!

5

How is lithium excreted?

Entirely renal excretion

6

Effect of Carbonic Anhydrase Inhibitors (ex. Acetazolamide) on Li?

Inhibit the proximal convoluted tubule from reabsorbing bicarbonate- Na and Li accompany bicarbonate, overall less Na and Li are absorbed, Li LEVEL GOES DOWN

7

Effect of osmotic diuretics (ex. Mannitol) on Li?

Increase tubular fluid osmolality at proximal convoluted tubule. Leads to an increase in the excretion of water and Na/Li, Li LEVEL GOES DOWN

8

Effect of loop diuretics (ex. Furosemide) on Li

Inhibit Na/K/Cl transport system in the thick ascending loop of Henle. uncertain effect on Li

9

Effect of Thiazide diuretic on Li

Inhibit Na/Cl reabsorbtion in the distal convoluted tubule, compensatory increase in reabsorbtion of Na and Li at the proximal convoluted tubule, Li LEVEL GOES UP

10

Effect of K sparing diuretics on Li

Act on collecting duct, decrease Na and Li reabsorption, Li LEVEL GOES UP

11

Effect of ACE Inhibitors on Li

Inhibits angiotensin II production, increase in Na and Li reabsorption in collecting duct, Li LEVEL GOES UP

12

Effect of Angiotensin II inhibitors on Li

Inhibits angiotensin II production, increase in Na and Li reabsorption in collecting duct, Li LEVEL GOES UP

13

Other things that can decrease the Li level

Aminophylline
Theophylline
Caffeine
Pregnancy

14

Other things that cause no change in Li level

Amiloride
Acetaminophen
Aspirin
Sulindac

15

Other things that cause increased Li level

NSAIDS
COX-2 inhibitors
Dehydration
Na Depletion
Renal Impairment
Advanced Age

16

Li Common Side Effects

hypothyroidism
Nausea
Diarrhea
Fine Tremor
Decreased concentration
Sedation
Weight gain

17

Li Rare Side Effects

Increased parathyroid

18

Li Serious Side Effects

Nephrogenic Diabetic Insipidus
Mild renal insufficiency
End stage renal disease
Li toxicity

19

Before starting Li check:

TSH
Renal Function
ECG (if patient >50 y/o)
Weight (BMI)
Pregnancy test

20

After starting Li, check:

Lithium level

21

When stable on Li, check___ every 6-12 months:

TSH
Renal function
Weight (BMI)
Li level

22

What is Depakote and what is the advantage to using over Valproic Acid?

Valproic acid & Sodium Valproate > pill that is enterically coated, decreased GI symptoms

23

Depakote MOA

Unknown, blockage of voltage dependent Na channels

24

Depakote protein binding

HIGHLY (90%) protein bound

25

Depakote Drug Drug Interactions

Protein displacement: Displaces other protein bound drugs (phenytoin, carbamazepine)
Can be displaced by caffeine and aspirin
Inhibits metabolism of anticonvulsants (carbamazepine, lamotrigine, phenytoin), risk of toxicity

26

Depakote Common Side Effects

Nausea, Vomiting, Diarrhea
Ataxia, headache, dizziness, tremor, sedation
Increased ammonia level, weight gain

27

Depakote rare side effects

thrombocytopenia, increased suicide risk, alopecia

28

Depakote Toxicity

Mild increase LFT's
Hepatotoxicity (child > 2 on sx med)
Hyperammonemia

29

Before starting depakote check:

LFTs
Platelet count
Weight (BMI)
Pregnancy test

30

After starting depakote check:

Valproic acid level

31

With depakote, when stable, every 6-12 months, check:

LFTs
Platelet count
Weight (BMI)
Valproic acid level

32

Carbamazepine Protein binding

Medium (70-80%) protein binding

33

Carbamazepine DDI

CYP450 effects
-increases metabolism of other drugs
-induces UDP-glucuronosyltransferases
-auto-induces its own metabolism
Other drugs can inhibit its metabolism
Other drugs can induce its metabolism
Take Away: It DOES NOT inhibit metabolism of other meds

34

Carbamazepine common SE

Nausea, vomiting, weight gain, teratogenic
1011 epoxide: ataxia, diploplia, dizziness, tremor, sedation

35

Carbamazepine rare SE

Stevens Johnson Syndrome
hepatotoxic
Aplastic anemia
Agranulocytosis

36

Lamotrigine protein bidning

Low protein binding (55%)

37

Lamotrigine metabolism

glucuronidation

38

Lamotrigine DDI

Depakote causes lamotrigine level to double
Oral contraceptives cause lamotrigine to halve
Carbamazepine cause lamotrigine to halve

39

Lamotrigine SE

rash (benign and Stevens Johnson Syndrome)
nausea

40

Second Generation Anti-psychotics for BD Indication

Severe Bipolar Mania (psychosis, suicidal/dangeous behavior)
Maintenance treatment
Only 3 for bipolar depression

41

Second Generation Anti-Psychotics Drug Combo

Li + SGA or
Depakote + SGA

42

Lithium Teratogenic risk

"increased risk of Ebstein's anomly" but risk is much lower than orginially thought

43

Depakote (Sodium Valproate) teratogenic risk

Greatest risk of serious birth defects of all psychotropic meds
Risk of neural tube defects
LAST resort in pregnant

44

Carbamazepine teratogenic risk

Neural tube defects

45

Lamotrigine teratogenic risk

Least teratogenic risk of mood stabilizers
Possible risk of cleft palate

46

Antipsychotics teratogenic risk

Same incidence of major physical malformation as general population (2-5%)

47

Risk of pregnant bipolar patient not taking medicaiton

Risk greatly increased of having a mood episode if untreated (37% w/ meds had a mood episode, vs. 85% w/o meds)

48

Which drugs can be used to treat Bipolar I Manic episode Severe:

Lithium
Depakote
FGA's (1st gen anti-psychotics)
SGA's
Benzos (adjunct)

49

Which drugs can be used to treat Bipolar I Manic Non-severe or Bipolar II Hypomanic

Lithium
Depakote
Carbamazapine
FGA's
SGA's
Benzo's (adjunct)

50

Which drugs can be used to treat Bipolar I Maintenance?

Continue what worked in treating the acute episode

51

Which drugs can be used to treat Bipolar II Maintenance?

Continue what worked in treating the acute episode

52

Which drugs can be used to treat Bipolar I or II Depression?

Lithium
Depakote?
Lamotrigine
Some SGA's
Anti-depressants?
Benzo's (at times)

53

Lamotrogine Indication

Good for treating bipolar depression, or maintenance Rx
NOT useful in treating bipolar I/II manic/hypomanic episodes