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Bipolar Pharma

Behavioral Medicine Pharmacology

Bipolar: theories monoamine,dysregulation, anticholinergic, kindling, neuroendocrine, membrane & cation hypothesis, secondary messenger system, biologic rhythms, switch phenomenon
Lithium MOA not well known; Block DA rec sensitivity; inc NE release in depn; dec NE release in mania; reduces beta-adrenergic stim of adenylate cyclase; inc 5-HT synth
Lithium indicated for acute mania; maintenance
Lithium advantages antidep & antimanic fx (no switching nec); prevent relapse; better than valproate at prevent suicide
Lithium: best results in pts: Fewer prior episodes; hx euthymia; Periods of good functioning; Pos FH w/Lithium
Lithium: reduced fx: severe mania w/psychotic; mixed episodes; rapid / continuous cycling; etoh/ drug abuse
Lithium dosing start at 600-900; inc by 300 q 2-3d (target 900-2400)
Lithium Monitoring Draw trough 12h post last dose (tx day 5); then 1-2 wks for 1st mos; 5 days post dose change
Lithium tx serum level 0.8 to 1.2 mEq/L (acute manic: poss 1.2 – 1.5); SR has no ref range
Lithium half life usu 24 h (8 – 20 h in mania)
Lithium AE (early) Blocks ADH fx on its receptors (polydipsia / polyuria); mx weakness; fine hand (intentional) tremor
Lithium AE (late) NDI; increased lytes (Na, K, H2O), Cr; cardiac; persistent neuro probs (memory loss; MG, EPS); thyroid; GI; inc WBC & wt
Leading cause of lithium noncompliance loss of creativity / memory
Lithium toxicity factors Na restriction; dehydration; drug interactions
Lithium: mild toxicity = 1.5 – 2.0; prob memory/conc; GI; tremor
Lithium: moderate toxicity = 2.0-2.5; confusion, ataxia, nystagmus, inc DTR
Lithium: severe toxicity = over 3.0; Choreoathetosis, seizure, coma, death
Tx lithium tox (>2.5) d/c lithium; gastric lavage; monitor levels
Tx lithium tox (>3.5) d/c d/c lithium; hemodialysis; monitor levels
Lithium CI Renal dz; severe CV dz; hx leukemia; first tri of PG; hypersensitivity; breastfeeding?
Drugs that have anti-kindling properties anticonvulsants (Valpro, carbamazepine, lamotrigine)
Bipolar drugs: category D (avoid in PG, dc in first trimester): lithium, valpro, carba
Valpro MOA Unk; prob inhib GABA metab &stim GABA synth
Valpro good for: FDA: acute mania, rapid cycling (> lithium at mixed, secondary bipolar, subst induced)
Valpro less good for: depression
Valpro absorption delayed: with food
Valpro AE GI, sedation, ataxia/tremor, low plt, liver probs
Carbamazepine MOA Unk; prob block voltage-sensitive Na+ channels; Block CA+ influx thru NMDA-glutamate receptor
Carbamazepine efficacy XR same as lithium; also acute mania, prophylaxis, bipolar depn
Carbamazepine better than lithium: Severe mania; Rapid cycling; Mixed episodes
Carbamazepine dosing start 200-400 mg/d; target 400-2400; max 15mg/kg/d
Carbamazepine monitoring no est tx level; anticonvulsant = 6-12 mcg/ml; carba levels 12h postdose & day 6
Carbamazepine PK well absorbed (not affected by food); peak levels in 1-5 hr; 80% pro bound
Carbamazepine AE CNS tox; GI (divide doses); leukopenia, hepatotox, low plt; SIADH, osteomalacia, derm
Carbamazepine potentially lethal: >15 mcg/ml
Carbamazepine CI bone marrow depn; hypersensitivity
Lamotrigine MOA Blocks voltage-sensitive Na+ and Ca+ channels
Lamotrigine efficacy maintenance (esp bipolar depn); NOT for acute mania
Lamotrigine PK well absorbed (not affected by food); peak levels 1-4 hr; half life 25 hr (so x1/d dose) (inc to 60 hr w/valpro)
Lamotrigine AE usu well tolerated; Stevens Johnsons syndrome; rash
antipsychotics dosing Risperidone, olanzapine, quetiapine: mono or combo w/valp or lithium; aripiprazole, ziprasidone: monotx
antipsychotics good for: acute mania; mixed (Quetiapine: bipolar depn)
SSRIs in bipolar depn monotx inappropriate; high uncertainty in risk to manic switch
Benzo: benefit in bipolar Reduce insomnia and agitation in acute mania
CCBs: benefit in bipolar in lithium pts unable to tolerate AE
Created by: Abarnard