Pharm: mood stabilizers

Question 1

MOA of lithium carbonate

Answer 1

Most common tx for BPD ** very narrow TI, not very safe!

** Li interferes w/ resynthesis of PIP2, leading to its depletion in CNS by disrupting IP3/DAG

MOA:

• inhibits phosphatase enzyme thus blocking the IP2 –> IP1 –> inositol : thus blocks the intracellular GPCR PIP2 signaling cascade
• ** With chronic lithium treatment there is a depletion of phosphatidylinositol-4,5-bisphosphate (PIP2)– the source of the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG) **
• A depletion of PIP2 may lead to a decreased responsiveness to synaptic transmission
• depletion of PIP2 sufficient enough to produce decreased responsiveness may not occur until lithium has been administered for 2-3 weeks

Other MOA’s:

• acts on electrolytes (substitutes Na+)
• effects on NT systems (DA, 5-HT, Ach)
• takes 2-3 weeks for effects to be seen!

Question 2

divalproex sodium / Valproate

Answer 2

anticonvulsant used for BPD= valproic acid + sodium valproate

• • first line tx for bipolar disorder
• • faster onset than lithium used in acute setting (4-5 days)
• • wider TI

MOA: increased GABA levels, blockade of Na+ channels

ADR:

• GI (N&V) & hepatic problems
• Congenital neural tube defects
• Alopecia (hair loss), weight gain, hisuitism
• Increases polycystic ovarian syndrome in women up to nine fold

Question 3

carbamazepine

Answer 3

= anticonvulsant used for BPD

MOA: blockade of voltage dependent sodium channels

** Pharmacokinetic tolerance through auto-induction of metabolism

SE: aplastic anemia and agranulocytosis! (not used as often now)
- Hyponatremia (~3%), diplopia, ataxia, GI upset, sedation, weight gain

Question 4

what are used for mood stabilizers?

Answer 4

• lithium carbonate
• valproate
• carbamazepine
• lamotrigine
• atypical antipsychotics

Question 5

lamotrigrine

Answer 5

= anticonvulsant used for BPD

USE: Not effective in acute mania, used instead for maintenance therapy and prevention of occurance

MOA: Blocks sodium and/or calcium channels.

ADRs: dizziness, headache diplopia, GI upset, somnolence, skin rash * Steven Johnson Syndrome*

** Slow taper in dosing is critical

DDIs:

• valproic acid doubles [lamotrigine]
• carbamazepine halves [lamotrigine]

Question 6

CI in pregnant pts?

Answer 6

valproic acid! carbamazepine, Lithium

Li: has causes congenital cardiac abnormalities, lower apgar scores, neuro toxicity

valproate: causes NT defects, cardiac effects

Car: also causes NT defects

Lamotrigine has lowers risks in pregnancy but still has AE of midline clefts

Question 7

CI in pregnant pts?

Answer 7

valproic acid! carbamazepine, Lithium

Question 8

carbamazepine

Answer 8

= anticonvulsant used for BPD

SE: aplastic anemia and agranulocytosis! (not used as often now)

Question 9

AE’s of Lithium?

Answer 9

• • tremor, thirst, polyuria, edema, w/g **
• hypothyroidism
• renal dysfunction (nephrogenic polydipsia & polyuria)
• cardiac conduction problems
• gastric distress
• mild cognitive impairment
• edema
• weight gain

Question 10

TI of Lithium:

Answer 10

VERY NARROW!

plasma drug levels must be monitored:
acute ~ 1-1.5 meq/L
maintenance ~0.6 - 1.2 meq/L
toxic levels ~ 2.0 meq/L

• • DEHYDRATION can lead to toxic levels quickly due to increased plasma concentrations and decreased renal excretion
• • Volume depletion or renal impairment from any cause increases lithium reabsorption. Examples of such conditions include gastrointestinal losses, acute decompensated heart failure, cirrhosis, and the administration of diuretics, NSAIDs, or angiotensin converting enzyme inhibitors.
• • Many commonly used drugs, including NSAIDs, ACE inhibitors and diuretics, can increase serum lithium concentrations

20-40% of bipolar patients do not respond to lithium

Question 11

atypical antipsychotics used for tx BPD?

Answer 11

Aripiprazole (Abilify)
Olanzapine (Zyprexa)  Olazapine + fluoxetine (Symbyax)
Lurasidone (Latuda)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)

Question 12

SJS?

Answer 12

Lamotrigine and Carbamazepine

Question 13

PCOS and hairloss?

Answer 13

think divalproex

Question 14

epidemiology of BPD?

Answer 14

Lifetime prevalence rate is 0.7 to 1.6%

First degree relatives 24-times more likely to develop bipolar disorder

Average onset age 21, however first symptoms often present in teen years or earlier

Question 15

increased risk of weight gain?

Answer 15

cloazapine, olanzapine, quetiapine

Question 16

AE’s of Lithium?

Answer 16

** tremor
hypothyroidism
renal dysfunction (polydipsia & polyuria)
cardiac conduction problems
gastric distress
mild cognitive impairment
edema
weight gain

Question 17

TI of Lithium:

Answer 17

VERY NARROW!

plasma drug levels must be monitored:
acute ~ 1-1.5 meq/L
maintenance ~0.6 - 1.2 meq/L
toxic levels ~ 2.0 meq/L

** DEHYDRATION can lead to toxic levels quickly due to increased plasma concentrations and decreased renal excretion

20-40% of bipolar patients do not respond to lithium

Question 18

aplastic anemia and agranulocytosis

Answer 18

think carbamazepine

Question 19

SJS?

Answer 19

Lamotrigine

Question 20

PCOS and hairloss?

Answer 20

think divalproex

Question 21

which drugs cause increased DM SE?

Answer 21

clozapine, olanzapine

Question 22

increased risk of weight gain?

Answer 22

cloazapine, olanzapine, quetiapine

Question 23

PK of lithium?

Answer 23

small cation thats eliminated primarily in the urine

rapidly absorbed in GI

half life: 18 hours in adults, 36 hours in elderly

Question 24

tx of depression assoc. w/ BDP?

Answer 24

lithium is protective against suicide and self-harm

also antipsychotics: quetiapine, olanzapine and fluoxetine

Question 25

maintenance therapy tx?

Answer 25

lithium alone or in combo w/ valproate, carbamazepine, lamotrigrine

Question 26

tests to run before starting tx w/ Li?

Answer 26

renal function, thyroid function

Question 27

signs of Li toxicity?

Answer 27

tremor, dysarthria, delirium, coma, seizures, ANS instability