2-16 Bipolar Rx Flashcards
Lithium
- Indications (3)
- Onset
- How does it impact neurotransmitters and their release (on 5-HT? NE/DA? Ach synthesis?)
- (1) [first line tx: Bipolar disorder], (2) [acute & maintenance tx: mania/bipolar depression] (3) [Suicide Reduction: Bipolar 1 and 2]
- Delayed onset (2-3 weeks for full effect)
- Increases effects of 5–HT, decreases turnover of NE and DA, increases synthesis of Ach
Li Pharmacokinetics
- Absorption from where?
- Protein binding?
- Wide or narrow therapeutic window?
- Metabolism/excretion?
- Well absorbed from the GI tract
- No protein binding in the blood
- Very narrow therapeutic window (smallest of all psychiatric drugs)
- Excretion/ metabolism is fully renal (NO HEPATIC MET.)
In general, how is the excretion of lithium affected by diuretics that work on different components of the nephron?
Excretion of lithium decreases as you progress through the nephron. Diuretics that operate in the PCT increase Li excretion, diuretics which work on the LOH have an unclear affect on Li, and diuretics for the DCT or CD decrease Li excretion.
Key Li SE’s?
- Derm? (4)
- Endocrine? (2)
- Neuro? (3)
- Weight?
- Renal? (2)
- Heme (1)
- GI (2)
- Cardiac (1)
- Derm: Acne, rash, psoriasis, alopecia
- Endocrine: hypOthyroidism, [Hyperparathyroidism (rare)]
- Neuro: [Fine tremor], [twitches/nystagmus], sedation
- Weight: Weight gain
- Renal: [Nephrogenic Diabetes Insipidus] and [ESRD potential]
- Heme: Increased WBC’s
- GI: Nausea, diarrhea
- Cardiac: rare syncope w/ severe lithium toxicity
Depakene vs Depakote
(What is the other name for each and how do their side effects differ/why?)
Depakene- aka valproic acid. Liquid that is hard on the stomach and must always be taken with food.
Depakote- aka divalproex sodium. (1:1 molar ratio of valproic acid and sodium valproate). Coated in powder that decreases the nausea and diarrhea seen w/ depakene
Depakote key drug-drug interactions (3) and AE’s (7)
- (1) Has high levels of protein binding (90%) so displaces other protein bound drugs (including phenytoin) and can itself be displaced by caffeine/aspirin (2) inhibits hepatic metabolism (3) inhibits metabilism of other anticonvulsants
“Grab a Coat..you’ve got GNATTTS!
- AE’s: (1) NVD, (2) Thrombocytopenia at high doses, (3) [Gain in wt], (4) Alopecia, (5) Tremor (6) Sedation, (7) TERATOGENIC
- Carbamazepine (Tegretol) DDI’s are due to what specific interaction?
- SE’s (1 for each category)
- Derm
- GI
- Heme
- Neuro
- Hepatic
- Pregnancy
- DDI’s are via Cyp450
- Derm: Rare potential for Steven Johnson Syndrome
- GI: N/V
- Heme: rarely anemia
- Neuro: dizziness/sedation
- Hepatic: rarely hepatotoxic
- Pregnancy: potential teratogenicity (NTDs)
- MOA for Lamotrigine (2)
- Key DDI’s (3) and the exact effect this has on lamotrigine levels
- (1) Inhibits release of glutamate (2) inhibits Na+ channels
- Depakote –> lamotrigine level doubles
- Oral contraceptives –> lamotrigine level cut in half
- Carbamazepine –> lamotrigine level cut in half
Lamotrigine AE’s
- Derm (1)
- GI (2)
- Heme (1)
- Neuro (3)
- Other
- Derm: Rash! (sometimes benign, sometimes Stevens Johnson Syndrome but hard to tell them apart at first).
- GI: N/V
- Heme: Blood dyscrasias (abnormal issues w/ blood including aplasticity)
- Neuro: double vision, ataxia, HA
- Other: Insomnia
Teratogenic risks for…
- Lithium?
- Carbamazepine?
- Lamotrigine?
- Sodium valproate (depakote)?
- Lithium: .05-.1% (slightly higher than general population risk)
- Carbamazepine: 1% risk (moderately higher than general population risk)
- Lamotrigine: least teratogenetic risk
- Depakote: Greatest risk of serious birth defects of all psychotropic meds. RIsk of NTDs = 12-16x gen population rate.
Depakote > Carbamazepine > Lithium > Lamotrigine
Tx for Bipolar I Manic episode (Severe) (5)
How well do antidepressants work?
Treat Bipolar pts b4 they go BALD!
- Benzos (ONLY AS ADJUNCT)
- AntiPsychotics (1st AND 2nd Generation)
- Lithium **
- Depakote **
NO ANTIDEPRESSANTS
Tx for [Bipolar I manic Non-severe] or [Bipolar II hypOmanic] (6)
Treat Bipolar pts b4 they go BALD!
- Benzos (ONLY AS ADJUNCT)
- AntiPsychotics (1st AND 2nd Generation)
- Lithium **
- Depakote **
- [Carbamazepine Tegretol]
Tx of Bipolar I or II Depression (6)
- Lithium
- Depakote (sometimes)
- Lamotrigine
- SGA’s (some)
- Anti-depressants (some)
- Benzos (at times)
Although the exact MOA is unknown for Li, it most likely involves what?
2nd messenger enzymes
What specific factors (including but not limited to diuretics), DEC Li levels? (6?)
- Acetazolamide
- Mannitol
- Aminophylline
- Theophylline
- Caffeine
- Pregnancy
What specific factors (including but not limited to diuretics), have no effect on Li levels? (5)
- Furosemide (Lasix)
- Amiloride
- Acetaminophen
- Aspirin
- Sulindac
What specific factors (including but not limited to diuretics), INCREASE Li plasma levels? (10)
- Thiazides
- K+ sparing diuretics
- ACE Inhibitors
- Angiotensin II
- NSAIDS
- COX-2 inhibitors
- Dehydration
- Na+ depletion
- Renal impairement
- Advanced age
(5) key tests before starting a patient on lithium
- TSH
- Renal Function
- ECG (If >50 y/o)
- BMI
- Pregnancy test
Depakene/ Depakote Side Effects
- Derm (1)
- GI (3)
- Heme (1)
- Neuro (2)
- Other (3)
- Derm: alopecia (rare)
- GI: N/V/D
- Heme thrombocytopenia at higher doses
- Neuro: tremor, sedation
- Other: weight gain, polycystic ovarian syndrome (PCOS), suicide risk (rare)
“Grab a Coat…you’ve got GNATTTS!”
Effects of [Depakote/Depakene] Toxicity (3)
- Mild increase LFT’s
- Hepatotoxicity
- Hyperammonemia
(4) Key tests before starting patient on Depakote
- LFT’s
- Platelet count
- BMI
- Pregnancy test
“Grab a Coat…you’ve got GNATTTS!”
How does Carbamazepine affect its own metabolism? What effect does this have on its halflife
Because it induces multiple CYP450 enzymes, it increases metabolism of many drugs, including auto-induction of its own metabolism! This decreases its half life.
Lamotrigine
Protein binding (high or low?)
How is it primarily metabolized?
- Low protein binding
- Primarily metabolized via glucuronidation
What is the use of Second Generation Antipsychotics in tx of bipolar disorder
Can be used to treat acute mania (severe bipolar mania-psycosis and suicidal/dangerous behavior)
What factor increases Lamotrigene side effects?
Alcohol
Li+ toxicity symptoms when the Li+ level is Mild (1.5-2.0mEq/L)
- GI? (3)
- State of consciousness? (2)
- Neurologic? (2)
- Cardiac? (0)
- GI: N/V/D
- SOC: Lethargy, drowsiness
- Neuro: Muscle weakness, coarse hand tremor
- Cardiac: none
Li+ toxicity symptoms when the Li+ level is Moderate (2.0-2.5 mEq/L)
- GI? (0)
- State of consciousness? (1)
- Neurologic? (3)
- Cardiac? (1)
- GI: none
- SOC: Confusion
- Neuro: Myoclonic twitches, Dysarthria Nystagmus, Ataxia
- Cardio: ECG changes
Li+ toxicity symptoms when the Li+ level is Severe (>2.5 mEq/L)
- GI? (0)
- State of consciousness (2)
- Neurologic? (2)
- Cardiac? (1)
- GI: none
- SOC: Grossly impaired consciousness, coma
- Neuro: increased deep tendon reflexes, seizures
- Cardio: Syncope
________ __________ (general class of drugs) are FDA approved and are the most frequently used in the treatment of the different phases of bipolar disorder.
Mood stabilizers
Lithium indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute mania
- Maintenance
- Bipolar depression
Valproic Acid (Depakene) indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute mania
- Maintenance
Carbamazepine indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute mania
- Maintenance
Lamotrigine indications
(Acute mania, maintenance, and/or bipolar depression?)
- Maintenance
- Bipolar Depression
- Which antipsychotic generation is only approved for treatment of acute mania?
- Which drugs are in this classification? (2 key ones)
- First generation antipsychotics
- Haloperidol (and other high potency FGA’s) and Chlorpromazine
Risperidone indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute Mania
- Maintenance
Geodone indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute mania
Lurasidone indications
(Acute mania, maintenance, and/or bipolar depression?)
- Bipolar Depression
Olanzapine indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute Mania
- Maintenance
Olanzapine + Fluoxetine (Symbyax) indications
(Acute mania, maintenance, and/or bipolar depression?)
- Bipolar Depression
Quetiapine indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute Mania
- Maintenance
- Bipolar Depression
Asenapine indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute mania
Aripiprazole indications
(Acute mania, maintenance, and/or bipolar depression?)
- Acute mania
- Maintenance