Bipolar Disorder Drugs

- grandiosity, decreased need for sleep, racing thoughts, speech, distractable, risky behavior
- manic episodes=marked disturbance in social/occupational situations
- DIGFAST
- distractability
- increased psychomotor agitation
- grandiosity
- flight of ideas
- activities that are dangerous
- decreased need for sleep
- talkative
- need 3/7

1. presence of manic episodes w/ major depressive episodes
2. presence of hypomanic episodes w/ major depression- hypomania means pt will not have severe social and occupational impairment

1. mania and depression episodes occurring withing 24 hrs- have poorer prognosis
2. when 4 major depressive or manic episodes occur in 12 mos

1. desynch of circadian or seasonal rhythm
2. hypomania/mania can be enjoyable. clouding, sedation, and wt gain with meds

- manic episode- in a few days pt will come back feeling really good, in unipolar depression takes longer than that
- usually will have more depressive episodes

1. substance abuse problems
2. personality disorders
3. careful hx, get hx from FAM, use mood disorder questionnaire

1. avoidance of triggers--sleep deprivation, DA augmenting agents, alcohol intox, corticosteroids, and antidepressants (w/o mood stabilizer)
2. bilateral ECT- good for acute mania and acute depression- good for pregnant pts
3. psychoeducation- dec stress and early signs of episodes

1. acute manic episode - in which full therapeutic benefit seen in greater than 3 wks
2. prophylaxis-- helps reduce high relapse rate for bipolar mania and depression, prevents suicide and self injury
- gold std for bipolar disorder
- pts w/ rapid cycling or mixed states may NOT respond as well to Li monotherapy
- avoid in pts w/ unstable renal disease

- lots of diff theories-- may modulate gene expression and will have neuroprotective effects

- renal excretion, excreted unchanged, and first order linear kinetics
- has very narrow theraputic index- reaches steady state after 5 days
- takes 3 wks to see full effects

- GI, intentional tremor
- increased urination, and thirst
- long term-- may have mild wt gain and acne
- can divide doses to improve GI sx
- can lead to hypothyroidism
- rare renal damage

- dose-high dose coarse tremor and low dose fine tremors
- risk factors include advanced age, stress, fam hx, hihg Li concentration, and caffiene

1. hypothyroidism, can tx w/ levothyroxine
2. No not dose dependant

1. LIthium via inhibition of ADH sensitive adenylate cyclase
2. reduce dosing

1. 1.5
2. GI
3. cognitive

- renal impairment--decreased Li clearance
- fluid restriction can increase Li
- Drug interactions w/ meds which alter Li excretion

- dont used NSAIDs, ACE Inh/ ARBs
- NSAIDs-- b/c reduce RBF
- ACE inh or ARBs- dec resistance at efferent arteriole-- reduces GFR
- thiazide diuretics b/c causes no reabsorption in distal tubules-- decreases excretion of Li and increases serum levels

- pregnancy is relative CI esp in front trimester-- may lead to some card malformations, floppy baby synd, and neonatal hypothyroidism

- Li serum concentrations
- baseline CBC
- SCr/NUM
- TSH levels

- neurons become super sensitive to firing and NEIGHBORING neurons are also recruited
- epilepsy

Class: Anticonvulsant agent
MOA: enhances inhibitory effect of GABA -- which will calm areas that are over excited in the brain

- good for rapid cyclers, mixed mania, and acute mania
- better for mania than depression

- long term-- wt gain, polycystic ovard syndrome
- hepatotoxicity, neutropenia, thrmobocytopenia

- pregnancy

Class: Anticonvulsant agents
MOA: Enhances inhib action of GABA and prevents the high frequency repetitive neuronal firing

- to tx acute mania, is a second or third line agent
- is not good for txing bipolar depression

- aplastic anemia and agranulocytosis- black box warning
- hyponatremia

- MOA: inactivates voltage sensitive Na channels and modulates or reduces release of glutamate
- Use: minimal benefit in stablizing mania but more effective than Li for preventing depression
- used as add on for tx-refractory bipolar depression
- no wt gain. sedation, blood level monitoring nor cognitive dulling
- but VERY slow initiation to minimize risk of rash

AE- black box rash warning--such as stevens johnson syndrome
DI: valproate decreases clearance which increases risk of rash-- moniter before and after for rash assessment

- sig wt gain w/ risk of new onset diabetes and increased TGs

- olanzapine
- benzodiazepines- SGA

- fast acting drugs-2-4 days
- adjunctive therapy

MOA: enhance GABA activity and calms the overexcited brain
Use: alleviate agitation and insomnia w/ mania and hypomania. Also improve sleep so facilitate recovery. NOT for core sx and do NOT prevent relapses
- Should NOT be used for greater than 1 mo

Benzodiazepines

- the mood stabilizers
- also rem anti depressants are linked w/ episodes of hypomania/mania-- esp in young pts, pts w/ hx of switching antidepressants, and rapid cycling

- SSRIs and buppropion(NDRI) are better than TCAs
- TCAs are well documented to be really bad for bipolar pts

- should make sure pt is on mood stabilizing drug

- benzodiazepines and antipsychotics
- use SGAs over benzos

- lithium and lamotrigine, antidepressants are not used becasue can ppt attack

- SGAs and electroconvulsant therapy

- plasmid mediated production of group transferases which inactivate the drug
- Amikacin

PK: not absorbed by GI tract, usually require IV or IM
AE: ototoxiicty, nephrotoxicity, NM blockade, and skin rxns

Use- aerobic gram (-) organisms, strict anaerobes are resistant
- often used w/ beta lactam drugs synergistically

- inhibit binding of aminoacyl t RNA to the mRNA ribosomal complex
- bind to 30S subunit, are bacterioSTATIC

- efflux of drugs by plasmid coded efflux protein pump= TEST Q
- altered drug permeability/enzymatic inactivation of the drug

PK: oral, does not absorb well into the CNS
AE: hepatotoxicitiy, teeth discoloration
Use: BROAD spectrum- both gram - and gram +
- also works of rricketsiae, chlamydiae, and mycoplasma infections

- bind ot 50 S subunit and inhibit the peptidyl transferase- in transpeptidation
- bacterioSTATIC

- production of plasmid coded drug inactivating enzyme-- chloramphenicol acetyltransferase

- GI tract absorption, well distributed in body including the CSF
- hepatic inactivation

- Grey baby syndrome
- bone marrow suppression- inhibition of mitochondrail ribosomes
- aplastic anemia