bipolar meds

Question 1

lithium mechanism of action

Answer 1

reduces NE and dopamine sensitivity in CNS
inhibits dopamine synthesis
enhances GABA sensitivity, normalizes levels in CNS
inhibits inositol phosphatase secondary messenger system

Question 2

SE of lithium

Answer 2

dyspepsia, GI upset, about 20% weight gain, decreased cognition
dose related SE - tremor, sedation, lethargy, polyuria, polydypsia, inc cognitive dulling and GI upset

Question 3

LI toxicity

Answer 3

> 1.5 mEq/L, course tremor/twitching, dizzy/syncope, confusion, slurred speech, ataxia, convulsions, stupor,
2.5 coma, death

Question 4

Lithium SE

Answer 4

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

Question 5

Li drug interactions

Answer 5

ACEi/ARB-inc Li 200-300%
NSAID/Cox2 inh 50%

Inc renal blood flow caused by caffeine/theophylline - dec Li levels

Question 6

Inc r/f neurotoxicity with Li

Answer 6

antipsychotics, SSRI, TCA, CCB, carbamezapine

Question 7

Li dosing

Answer 7

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

Question 8

Li therapeutic index

Answer 8

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

Question 9

Li monitoring

Answer 9

THS, Chem 7 (BUN, Cr, electrolytes) HCG, baseline ECG, Wt, CBC (leukocytosis)

Question 10

Valproic Acid us and mechanism

Answer 10

wide therapeutic window
preferred in mixed episodes, rapid cyclers
Na channel blocker
decreases glutamine release
stabilizes K channels
enhances GABA activity

Question 11

valproate to valproic acid: divalproex to valproic acid

Answer 11

stomach; small intestine

Question 12

valproic acid SE

Answer 12

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

Question 13

Valproic acid dosing

Answer 13

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

Question 14

Valproic acid monitoring

Answer 14

baseline, monthly for 2 mos, then 3-6 mos, CBC, LFT. weight, amonia (if altered MS), serum levels
pregnancy

Question 15

Carbamazepine (tegretol)

Answer 15

second line, good for rapid cycling/mixed episodes/atypical presentation
auto-induction
ER - equetro
Mechanism - augmentation of GABA

Question 16

Carbamazepine SE

Answer 16

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

Question 17

carbamazepine interactions

Answer 17

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

Question 18

carbamazepine therapy

Answer 18

start 200 mg BID titrate to response
400-800 mg daily
therapeutic level for seizure 6-12 mg/ml

Question 19

CBZ lab monitoring

Answer 19

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

Question 20

lamotrigine (lamictal)

Answer 20

maintenance of bipolar only
good for rapid cycling
mechanism - inhibits Na channels, inhibits release of glutamate

Question 21

lamotrigine SE

Answer 21

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

Question 22

lamotrigine dosing

Answer 22

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

Question 23

oxycarbazepine

Answer 23

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

Question 24

antipsychotics and pregnancy

Answer 24

Class C, not associated with teratogenic risk
affects on prolactin and may lead to hyperprolactinemia, infertility
some associated with low birth weight

Question 25

mood stabilizer indications and classes

Answer 25

indications: bipolar, cyclothymia, schizoaffective, impulse control and intermittent explosive disorders
Classes: lthium and anticonvulsants