Lecture 77: Moodstabilizers Flashcards
Mood stabilizers might treat…(3)
Acute mania, mania recurrence, mania OR depression w/out worsening other pole of illness
3 main classes of mood stabilizers
Lithium, anticonvulsants, antipsychotics
Agents approved for Bipolar I disorder by stage of illness and key drugs (5 in total, 1 repeat)
Acute: lithium, valproate, carbamazepine ER; maintenance: lithium, lamotrigine; acute depression: no key drugs
T/F: Hard to treat depression in bipolar
True, traditional medications can –> mania; some people try to add antidepressant to mood stabilizer but no good data
Therapeutic use of lithium
Mania, bipolar maintenance; off-label: rage, MDD, schizophrenia, anti-suicide
Lithium and NT signaling (2) findings…take home point?
Balances excitatory and inhibitory effects of various NTs, enhances 5-HT release; THESE ARE THEORIES
Lithium and 2nd messenger system
Modifies cAMP levels and down-regulates PKC via PI system
Lithium and neuroprotective effects (2 main)
Prevents cell death and apoptosis, induces neurotrophic proteins via NMDA receptors
Where is lithium absorbed? Protein bound? Metabolized? Excreted? Why is this important?
GI; not protein bound OR metabolized; excreted almost completely unchanged in urine; cannot be given to people with kidney disease
Stead state plasma levels in?
4-5 days
What kinds of drugs increase lithium excretion?
Osmotic diuretics
What kinds of drugs decrease lithium excretion? (3) What else can increase lithium levels (3)
NSAIDs, ACE inhibitors, loop diuretics; kidney disease, low Na+ diet, dehydration
What underlies why dehydration increases lithium? Why does this matter?
Li+ and Na+ compete for absorption from proximal tubules; very narrow therapeutic window
Lithium renal SEs
Effects on tubular function (polyuria and thirst –> nephrogenic diabetes inspidus); effects on glomerulus (nephortic syndrome); tuberinterstitial nephritis (also called lithium induced nephropathy)
Which of the SEs of lithium is related to chronic use and is NOT reversible
Tuberinterstitial nephritis
Largely, lithium does what to the kidney?
Prevents urine concentration via vasopressin blocking
Other lithium SEs (8)
Hypothyroidism, tremor, N/V, cardiac (depression of sinus node), benign leukocytosis, cognitive dulling/impaired memory, teratogencity, psoriasis/acne
Lithium and pregnancy
Risk benefit conversation: can cause cardiac defect in fetus but may be better than manic pregnant woman
What are signs of lithium toxicity (neuro and renal)
Neuro: Chreoathetosis, ataxia, dysarthria, aphasia, confusion; renal: irreversible damage
What do we do to treat lithium toxicity
Stop drug, IV hydration, may need dialysis
How to prescribe lithium; avoid?
Check lithium, renal, thyroid function every 6-12 months; avoid abrupt cessation (could cause mania)
Valproate and BP disorder; mechanism? SEs?
Mania; enhances GABA, inhibits Na+; drug interactions (plasma protein binding, metabolized by p450); mostly GI, sedation, and pancreatitis/hepatoxicity, platelet problems
Carbamazepine and BP disorder
Mania
Lamotrigine and BP disorder
Maintenance
Valproate is associated with what interesting syndrome? Not first-line for what group of people?
Polycystic ovarian syndrome (weight gain, acne, menstrual irregularities); young women (also because of teratogenicity = neural tube defect)
Carbamazepine is a big…What does this cause? What else is weird?
Inducer of p450; induces hepatic metabolism of other drugs; INHIBITS its OWN metabolism (important for dosing)
Carbamazepine SE are similar to..Also can cause…
Valproate; Stevens-Johnson, blood dyscresia
Important drug interactions for Lamotrigine and a boxed warning
Valproate doubles serum levels while carbamazepine reduces levels; boxed warning = rashes (can be uncomplicated or SERIOUS)
Lamotrigine is LESS likely to be associated with…
Weight gain/cognitive side effects
