Bipolar - Lithium Flashcards
What’s the first line treatment?
Lithium
Acute Mania: Bipolar 1, 2, or Both?
Bipolar 1
Acute Hypomania: Bipolar 1, 2, or Both?
Bipolar 2
Bipolar Depression: Bipolar 1, 2, or Both?
Both
Bipolar Maintenance: Bipolar 1, 2 or Both?
Both
Can you treat bipolar with just an antidepressant?
No because you worry that it could flip them into a manic episode, so you need to give a mood stabilizer
Lithium is used for what parts of bipolar?
Everything! So…Acute Mania/Hypomania, Bipolar Depression, and Maintenance
Lithium is used as an adjunct for?
Major depression (b/c of increased effects of 5-HT)
A unique aspect of lithium is?
Reduces risk of suicide
How long does it take for Lithium to exert it’s full therapeutic effect?
2-3 weeks (delayed onset partially due to need to make dose adjustment)
Lithium is treated similar to what ion in the body?
Na+
Lithium’s effect on 5-HT? NE? DA? ACh?
Inc 5-HT effects
Dec turnover of NE and DA
Inc ACh synthesis
% of blood protein binding for Lithium?
0%
Describe Lithium’s therapeutic window.
Narrow!
0.6-1.2 meq/L
(>1.2 gives toxic effects)
Lithium metabolism/excretion is?
RENAL!
Diuretics that act at PCT do what? What are the 2 classes of these diuretics and the specific drug names (5 total)?
Urinary Alkalization
Carbonic Anhydrase Inhibitors - Acetazolamide, Dichlorphenamide, Methazolamide
Osmotic diuretics - Mannitol, Urea
Li MOA?
Inhibits Inositol recycling enzymes
Inhibits GSK-3
Affects Protein Kinase C
What happens to Li in the Glomerulus? PCT? Collecting Duct?
Glomerulus - freely filtered
PCT - reabsorbed with Na+
Collecting Duct - reabsorbed by principal cells epithelial Na+ channel
With PCT diuretics, Li levels: increase, decrease, or no change?
Decrease
Inc Li excretion gives decreased Li level in the body
With Loop of Henle diuretics, Li levels: increase, decrease, or no change?
No change (it’s controversial)
Name a loop diuretic.
Furosemide
With DCT diuretics, Li levels: increase, decrease, or no change?
Increases
What’s the relationship between diuretic site of action and Li excretion?
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)
What diuretics act at the DCT?
Thiazide
With Collecting Duct diuretics, Li levels increase, decrease, or no change?
Increases
What are the classes of drugs that act on the Collecting Duct? What are the specific drugs in these classes
K+ sparing - Spironolactone, Amiloride
ACE Inhibitors and Angiotensin II Receptor Antagonists - Aldosterone
What’s the MOA for Spironolactone?
K+ sparing diuretic
Antagonizes aldosterone receptors
Is it okay to be on both Li and Diuretics?
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.
What other things can give decreased Li levels?
Aminophylline
Theophylline
Caffeine
Pregnancy (hold Li during labor and restart it after birth on half the dose given during pregnancy)
What other things do not affect Li levels?
Amiloride
Acetaminophen
Aspirin
Sulindac
What other things give increased Li levels?
NSAIDs COX-2 Inibitors Dehydration Na depletion (hyponatremia) Renal impairment Advanced Age
Common Lithium Side Effects (7)
Hypothyroidism (F 5x >M) Nausea Diarrhea Fine Tremor (propanolol helps) Decreased concentration Sedation Weight gain (F > M)
Rare Li Side Effects (4)
Hyperparathyroidism
End Stage Renal Disease
Bradycardia
Sick Sinus Syndrome
Other serious Side effects from Li
NDI - Nephrogenic Diabetes Insipidus
Mild Renal Insufficiency
End Stage Renal Disease
What is NDI (Nephrogenic Diabetes Insipidus)?
Affects kidney’s ability to concentrate urine –> poluria gives polydipsia (inc fluid intake)
Is a long term risk of Li (10+ years of use)
What increases the risk for NDI?
Episodes of Li toxicity
What can be used to treat NDI?
Amiloride
Li Toxicity: Levels for Mild, Moderate, and Severe
Mild: 1.5-2.0 mEq/L
Moderate: 2.0-2.5 mEq/L
Severe: >2.5 mEq/L
If someone shows confusion, is there Li toxicity?
Assume so and try to rule it out
Mild Li toxicity gives? (7)
Nausea, Vomiting, Diarrhea
Lethargy, Drowsiness
Muscle Weakness
Coarse Hand Tremor
What do you do for mild Li toxicity?
Stop Li and resume lower dosage in a few days
Moderate Li toxicity gives? (6)
Confusion Myoclonic Twitches Dysarthria Ataxia Nystagmus ECG Changes
Severe Li toxicity gives? (5)
Grossly Impaired Consciousness Coma Inc DTR's (deep tendon reflexes) Seizures Syncope
Lab tests before Li treatment
Pregnancy test Renal Function Thyroid Function ECG if > 50 y/o BMI
Lithium levels and pregnancy
Lithium levels decreased during pregnancy and increase after delivery (due to GFR changes - in opp direction as Li level)
1st trimester exposure to Lithium has what associated defect?
Ebstein’s anomaly - congenial cardiac defects