Bipolar - Lithium

Question 1

What’s the first line treatment?

Answer 1

Lithium

Question 2

Acute Mania: Bipolar 1, 2, or Both?

Answer 2

Bipolar 1

Question 3

Acute Hypomania: Bipolar 1, 2, or Both?

Answer 3

Bipolar 2

Question 4

Bipolar Depression: Bipolar 1, 2, or Both?

Answer 4

Both

Question 5

Bipolar Maintenance: Bipolar 1, 2 or Both?

Answer 5

Both

Question 6

Can you treat bipolar with just an antidepressant?

Answer 6

No because you worry that it could flip them into a manic episode, so you need to give a mood stabilizer

Question 7

Lithium is used for what parts of bipolar?

Answer 7

Everything! So…Acute Mania/Hypomania, Bipolar Depression, and Maintenance

Question 8

Lithium is used as an adjunct for?

Answer 8

Major depression (b/c of increased effects of 5-HT)

Question 9

A unique aspect of lithium is?

Answer 9

Reduces risk of suicide

Question 10

How long does it take for Lithium to exert it’s full therapeutic effect?

Answer 10

2-3 weeks (delayed onset partially due to need to make dose adjustment)

Question 11

Lithium is treated similar to what ion in the body?

Answer 11

Na+

Question 12

Lithium’s effect on 5-HT? NE? DA? ACh?

Answer 12

Inc 5-HT effects
Dec turnover of NE and DA
Inc ACh synthesis

Question 13

% of blood protein binding for Lithium?

Answer 13

0%

Question 14

Describe Lithium’s therapeutic window.

Answer 14

Narrow!
0.6-1.2 meq/L
(>1.2 gives toxic effects)

Question 15

Lithium metabolism/excretion is?

Answer 15

RENAL!

Question 16

Diuretics that act at PCT do what? What are the 2 classes of these diuretics and the specific drug names (5 total)?

Answer 16

Urinary Alkalization

Carbonic Anhydrase Inhibitors - Acetazolamide, Dichlorphenamide, Methazolamide

Osmotic diuretics - Mannitol, Urea

Question 17

Li MOA?

Answer 17

Inhibits Inositol recycling enzymes
Inhibits GSK-3
Affects Protein Kinase C

Question 18

What happens to Li in the Glomerulus? PCT? Collecting Duct?

Answer 18

Glomerulus - freely filtered
PCT - reabsorbed with Na+
Collecting Duct - reabsorbed by principal cells epithelial Na+ channel

Question 19

With PCT diuretics, Li levels: increase, decrease, or no change?

Answer 19

Decrease

Inc Li excretion gives decreased Li level in the body

Question 20

With Loop of Henle diuretics, Li levels: increase, decrease, or no change?

Answer 20

No change (it’s controversial)

Question 21

Name a loop diuretic.

Answer 21

Furosemide

Question 22

With DCT diuretics, Li levels: increase, decrease, or no change?

Answer 22

Increases

Question 23

What’s the relationship between diuretic site of action and Li excretion?

Answer 23

As site of action moves from PCT to Loop of Henle to DCT, you go from increased Li excretion (PCT) to unclear changes (Loop) to decreased Li excretion (DCT)

Question 24

What diuretics act at the DCT?

Answer 24

Thiazide

Question 25

With Collecting Duct diuretics, Li levels increase, decrease, or no change?

Answer 25

Increases

Question 26

What are the classes of drugs that act on the Collecting Duct? What are the specific drugs in these classes

Answer 26

K+ sparing - Spironolactone, Amiloride ACE Inhibitors and Angiotensin II Receptor Antagonists - Aldosterone

Question 27

What's the MOA for Spironolactone?

Answer 27

K+ sparing diuretic Antagonizes aldosterone receptors

Question 28

Is it okay to be on both Li and Diuretics?

Answer 28

It's not really a problem with Furosemide but for other diuretics you have to monitor Li level to make sure it's therapeutic because of potential Li toxicity.

Question 29

What other things can give decreased Li levels?

Answer 29

Aminophylline Theophylline Caffeine Pregnancy (hold Li during labor and restart it after birth on half the dose given during pregnancy)

Question 30

What other things do not affect Li levels?

Answer 30

Amiloride Acetaminophen Aspirin Sulindac

Question 31

What other things give increased Li levels?

Answer 31

``` NSAIDs COX-2 Inibitors Dehydration Na depletion (hyponatremia) Renal impairment Advanced Age ```

Question 32

Common Lithium Side Effects (7)

Answer 32

``` Hypothyroidism (F 5x >M) Nausea Diarrhea Fine Tremor (propanolol helps) Decreased concentration Sedation Weight gain (F > M) ```

Question 33

Rare Li Side Effects (4)

Answer 33

Hyperparathyroidism End Stage Renal Disease Bradycardia Sick Sinus Syndrome

Question 34

Other serious Side effects from Li

Answer 34

NDI - Nephrogenic Diabetes Insipidus Mild Renal Insufficiency End Stage Renal Disease

Question 35

What is NDI (Nephrogenic Diabetes Insipidus)?

Answer 35

Affects kidney's ability to concentrate urine --> poluria gives polydipsia (inc fluid intake) Is a long term risk of Li (10+ years of use)

Question 36

What increases the risk for NDI?

Answer 36

Episodes of Li toxicity

Question 37

What can be used to treat NDI?

Answer 37

Amiloride

Question 38

Li Toxicity: Levels for Mild, Moderate, and Severe

Answer 38

Mild: 1.5-2.0 mEq/L Moderate: 2.0-2.5 mEq/L Severe: >2.5 mEq/L

Question 39

If someone shows confusion, is there Li toxicity?

Answer 39

Assume so and try to rule it out

Question 40

Mild Li toxicity gives? (7)

Answer 40

Nausea, Vomiting, Diarrhea Lethargy, Drowsiness Muscle Weakness Coarse Hand Tremor

Question 41

What do you do for mild Li toxicity?

Answer 41

Stop Li and resume lower dosage in a few days

Question 42

Moderate Li toxicity gives? (6)

Answer 42

``` Confusion Myoclonic Twitches Dysarthria Ataxia Nystagmus ECG Changes ```

Question 43

Severe Li toxicity gives? (5)

Answer 43

``` Grossly Impaired Consciousness Coma Inc DTR's (deep tendon reflexes) Seizures Syncope ```

Question 44

Lab tests before Li treatment

Answer 44

``` Pregnancy test Renal Function Thyroid Function ECG if > 50 y/o BMI ```

Question 45

Lithium levels and pregnancy

Answer 45

Lithium levels decreased during pregnancy and increase after delivery (due to GFR changes - in opp direction as Li level)

Question 46

1st trimester exposure to Lithium has what associated defect?

Answer 46

Ebstein's anomaly - congenial cardiac defects