bipolar meds Flashcards
lithium mechanism of action
reduces NE and dopamine sensitivity in CNS
inhibits dopamine synthesis
enhances GABA sensitivity, normalizes levels in CNS
inhibits inositol phosphatase secondary messenger system
SE of lithium
dyspepsia, GI upset, about 20% weight gain, decreased cognition
dose related SE - tremor, sedation, lethargy, polyuria, polydypsia, inc cognitive dulling and GI upset
LI toxicity
> 1.5 mEq/L, course tremor/twitching, dizzy/syncope, confusion, slurred speech, ataxia, convulsions, stupor,
2.5 coma, death
Lithium SE
excreted through kidney, caution with renal failure, dehydration ,NA depletion. , renal damage over 10 years, concentrates in thyroid - hypothyorid, benign heart arrhythmias and bradycardia
rarer-derm psoriasis, alopecia, folliculitis
Diabetes insipidus, leukocytosis
Li drug interactions
ACEi/ARB-inc Li 200-300%
NSAID/Cox2 inh 50%
Inc renal blood flow caused by caffeine/theophylline - dec Li levels
Inc r/f neurotoxicity with Li
antipsychotics, SSRI, TCA, CCB, carbamezapine
Li dosing
intial titration300 BID or TID, check levels 5-77 days after dose change, trough at 8-12 hours after last dose
titration-every 300 mg inc will lead to a 0.3 change in serum levels
as high as 1200-1800
30 to 450 BID is common, lower in elderly, higher when manic
Li therapeutic index
acute; 1.0-1.2 mEg/L
maintenance: 0.6 to 1.0 mEg/L
may take 5-10 days to see therapeutic effects,
maximal effects 2-3 weeks
abrupt withdraw ass. with high relapse rates
Li monitoring
THS, Chem 7 (BUN, Cr, electrolytes) HCG, baseline ECG, Wt, CBC (leukocytosis)
Valproic Acid us and mechanism
wide therapeutic window preferred in mixed episodes, rapid cyclers Na channel blocker decreases glutamine release stabilizes K channels enhances GABA activity
valproate to valproic acid: divalproex to valproic acid
stomach; small intestine
valproic acid SE
GI upset (anorexia, nausea, dyspepsia) add H2 antagonist, with food, enteric coated
Dose related SE - elevated liver, resting tremor, sedation, weight gain, somnolence, weakness, HA, thrombocytopenia
Rare SE - hepatic dysfunction, pancreatitis, hyperammonemia, alopecia
Toxicity- tremor, ataxia, nystagmus, visual hallucinations, coma
inc r/f neural tube defects
Valproic acid dosing
initial 500 mg qd to bid increase every few days, levels every 3-5 days, check 12h after last dose 50-125 mcg seizure control EC/ER, increase dose by 20% folic acid supplement in women
Valproic acid monitoring
baseline, monthly for 2 mos, then 3-6 mos, CBC, LFT. weight, amonia (if altered MS), serum levels
pregnancy
Carbamazepine (tegretol)
second line, good for rapid cycling/mixed episodes/atypical presentation
auto-induction
ER - equetro
Mechanism - augmentation of GABA
Carbamazepine SE
occur in 1st mo
dizziness, drowsiness, HA, diplopia, nystagmus, ataxia, blurred vision, nausea, weight gain
transient effects and may resolve with dose reduction
long term - menstrual and infertility problems
rare-SJS, aplastic anemia, agranulocytosis, thrombocytopenia, leukopenia
carbamazepine interactions
potent CYP 450 and 3A4 substrate
Inc CBZ - azole antifungal, macrolides, fluoxetine, fluvoxamine, cimetadine, protease inhibitors
CBZ dec - antidepressants, antipsychotics, benzos, OCP, thyroid hormone, warfarin, phenytoin, felodipine
carbamazepine therapy
start 200 mg BID titrate to response
400-800 mg daily
therapeutic level for seizure 6-12 mg/ml
CBZ lab monitoring
CBC with diff biweekly to monthly for 2 months, then every 3-6 months.
LFT every 6 mo
educate about s/sx of toxicity
fever, sore throat, mouth ulcers, rash, easy bruising
lamotrigine (lamictal)
maintenance of bipolar only
good for rapid cycling
mechanism - inhibits Na channels, inhibits release of glutamate
lamotrigine SE
common - dizziness, tremor, somnolence, HA, nausea, ataxia, diplopia
seizure withdraw in epileptic patients, needs 2 weeks d/c
rare serious SE, SJS, epidermal necrolysis, RASH - assoc with fast titration
lamotrigine dosing
start 12.5 to 25 mg QD
inc 25-50 mg q2 weeks
slow titration to 200-500 mg per day, usually BID
even slower if on valproic acid interaction with CYP 3A4
faster titration inc r/f rash
if stopped for 5 days, must restart at 25 mg again
oxycarbazepine
prodrug of carbamazepine metabolite second line initial dosing 300 mg BID, inc to 600 mg/day weekly, to 1200 mg total daily dose no auto-induction fewer drug-drug than CBZ inc metabolism of OCP
antipsychotics and pregnancy
Class C, not associated with teratogenic risk
affects on prolactin and may lead to hyperprolactinemia, infertility
some associated with low birth weight
mood stabilizer indications and classes
indications: bipolar, cyclothymia, schizoaffective, impulse control and intermittent explosive disorders
Classes: lthium and anticonvulsants
