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