Drugs to Treat Bipolar Disorder Flashcards
Lithium Clinical Use
First-line treatment
Acute mania, bipolar depression, maintenance treatment
Reduces risk of suicide (BP I, BP II, major depression)
How long does it take for Lithium to reach full therapeutic effect?
2-3 weeks
Lithium MOA
Unclear
- 2nd messenger enzymes
- effects neurotransmitters and release
- effects on electrolytes and ion transport (similar to Na)
Lithium protein binding
NONE!
How is lithium excreted?
Entirely renal excretion
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
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
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
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
Effect of K sparing diuretics on Li
Act on collecting duct, decrease Na and Li reabsorption, Li LEVEL GOES UP
Effect of ACE Inhibitors on Li
Inhibits angiotensin II production, increase in Na and Li reabsorption in collecting duct, Li LEVEL GOES UP
Effect of Angiotensin II inhibitors on Li
Inhibits angiotensin II production, increase in Na and Li reabsorption in collecting duct, Li LEVEL GOES UP
Other things that can decrease the Li level
Aminophylline
Theophylline
Caffeine
Pregnancy
Other things that cause no change in Li level
Amiloride
Acetaminophen
Aspirin
Sulindac
Other things that cause increased Li level
NSAIDS COX-2 inhibitors Dehydration Na Depletion Renal Impairment Advanced Age
Li Common Side Effects
hypothyroidism Nausea Diarrhea Fine Tremor Decreased concentration Sedation Weight gain
Li Rare Side Effects
Increased parathyroid
Li Serious Side Effects
Nephrogenic Diabetic Insipidus
Mild renal insufficiency
End stage renal disease
Li toxicity
Before starting Li check:
TSH Renal Function ECG (if patient >50 y/o) Weight (BMI) Pregnancy test
After starting Li, check:
Lithium level
When stable on Li, check___ every 6-12 months:
TSH
Renal function
Weight (BMI)
Li level
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
Depakote MOA
Unknown, blockage of voltage dependent Na channels
Depakote protein binding
HIGHLY (90%) protein bound
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
Depakote Common Side Effects
Nausea, Vomiting, Diarrhea
Ataxia, headache, dizziness, tremor, sedation
Increased ammonia level, weight gain
Depakote rare side effects
thrombocytopenia, increased suicide risk, alopecia
Depakote Toxicity
Mild increase LFT’s
Hepatotoxicity (child > 2 on sx med)
Hyperammonemia
Before starting depakote check:
LFTs
Platelet count
Weight (BMI)
Pregnancy test
After starting depakote check:
Valproic acid level
With depakote, when stable, every 6-12 months, check:
LFTs
Platelet count
Weight (BMI)
Valproic acid level
Carbamazepine Protein binding
Medium (70-80%) protein binding
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
Carbamazepine common SE
Nausea, vomiting, weight gain, teratogenic
1011 epoxide: ataxia, diploplia, dizziness, tremor, sedation
Carbamazepine rare SE
Stevens Johnson Syndrome
hepatotoxic
Aplastic anemia
Agranulocytosis
Lamotrigine protein bidning
Low protein binding (55%)
Lamotrigine metabolism
glucuronidation
Lamotrigine DDI
Depakote causes lamotrigine level to double
Oral contraceptives cause lamotrigine to halve
Carbamazepine cause lamotrigine to halve
Lamotrigine SE
rash (benign and Stevens Johnson Syndrome)
nausea
Second Generation Anti-psychotics for BD Indication
Severe Bipolar Mania (psychosis, suicidal/dangeous behavior)
Maintenance treatment
Only 3 for bipolar depression
Second Generation Anti-Psychotics Drug Combo
Li + SGA or
Depakote + SGA
Lithium Teratogenic risk
“increased risk of Ebstein’s anomly” but risk is much lower than orginially thought
Depakote (Sodium Valproate) teratogenic risk
Greatest risk of serious birth defects of all psychotropic meds
Risk of neural tube defects
LAST resort in pregnant
Carbamazepine teratogenic risk
Neural tube defects
Lamotrigine teratogenic risk
Least teratogenic risk of mood stabilizers
Possible risk of cleft palate
Antipsychotics teratogenic risk
Same incidence of major physical malformation as general population (2-5%)
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)
Which drugs can be used to treat Bipolar I Manic episode Severe:
Lithium Depakote FGA's (1st gen anti-psychotics) SGA's Benzos (adjunct)
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)
Which drugs can be used to treat Bipolar I Maintenance?
Continue what worked in treating the acute episode
Which drugs can be used to treat Bipolar II Maintenance?
Continue what worked in treating the acute episode
Which drugs can be used to treat Bipolar I or II Depression?
Lithium Depakote? Lamotrigine Some SGA's Anti-depressants? Benzo's (at times)
Lamotrogine Indication
Good for treating bipolar depression, or maintenance Rx
NOT useful in treating bipolar I/II manic/hypomanic episodes
