Lecture 77: Moodstabilizers

Question 1

Mood stabilizers might treat…(3)

Answer 1

Acute mania, mania recurrence, mania OR depression w/out worsening other pole of illness

Question 2

3 main classes of mood stabilizers

Answer 2

Lithium, anticonvulsants, antipsychotics

Question 3

Agents approved for Bipolar I disorder by stage of illness and key drugs (5 in total, 1 repeat)

Answer 3

Acute: lithium, valproate, carbamazepine ER; maintenance: lithium, lamotrigine; acute depression: no key drugs

Question 4

T/F: Hard to treat depression in bipolar

Answer 4

True, traditional medications can –> mania; some people try to add antidepressant to mood stabilizer but no good data

Question 5

Therapeutic use of lithium

Answer 5

Mania, bipolar maintenance; off-label: rage, MDD, schizophrenia, anti-suicide

Question 6

Lithium and NT signaling (2) findings…take home point?

Answer 6

Balances excitatory and inhibitory effects of various NTs, enhances 5-HT release; THESE ARE THEORIES

Question 7

Lithium and 2nd messenger system

Answer 7

Modifies cAMP levels and down-regulates PKC via PI system

Question 8

Lithium and neuroprotective effects (2 main)

Answer 8

Prevents cell death and apoptosis, induces neurotrophic proteins via NMDA receptors

Question 9

Where is lithium absorbed? Protein bound? Metabolized? Excreted? Why is this important?

Answer 9

GI; not protein bound OR metabolized; excreted almost completely unchanged in urine; cannot be given to people with kidney disease

Question 10

Stead state plasma levels in?

Answer 10

4-5 days

Question 11

What kinds of drugs increase lithium excretion?

Answer 11

Osmotic diuretics

Question 12

What kinds of drugs decrease lithium excretion? (3) What else can increase lithium levels (3)

Answer 12

NSAIDs, ACE inhibitors, loop diuretics; kidney disease, low Na+ diet, dehydration

Question 13

What underlies why dehydration increases lithium? Why does this matter?

Answer 13

Li+ and Na+ compete for absorption from proximal tubules; very narrow therapeutic window

Question 14

Lithium renal SEs

Answer 14

Effects on tubular function (polyuria and thirst –> nephrogenic diabetes inspidus); effects on glomerulus (nephortic syndrome); tuberinterstitial nephritis (also called lithium induced nephropathy)

Question 15

Which of the SEs of lithium is related to chronic use and is NOT reversible

Answer 15

Tuberinterstitial nephritis

Question 16

Largely, lithium does what to the kidney?

Answer 16

Prevents urine concentration via vasopressin blocking

Question 17

Other lithium SEs (8)

Answer 17

Hypothyroidism, tremor, N/V, cardiac (depression of sinus node), benign leukocytosis, cognitive dulling/impaired memory, teratogencity, psoriasis/acne

Question 18

Lithium and pregnancy

Answer 18

Risk benefit conversation: can cause cardiac defect in fetus but may be better than manic pregnant woman

Question 19

What are signs of lithium toxicity (neuro and renal)

Answer 19

Neuro: Chreoathetosis, ataxia, dysarthria, aphasia, confusion; renal: irreversible damage

Question 20

What do we do to treat lithium toxicity

Answer 20

Stop drug, IV hydration, may need dialysis

Question 21

How to prescribe lithium; avoid?

Answer 21

Check lithium, renal, thyroid function every 6-12 months; avoid abrupt cessation (could cause mania)

Question 22

Valproate and BP disorder; mechanism? SEs?

Answer 22

Mania; enhances GABA, inhibits Na+; drug interactions (plasma protein binding, metabolized by p450); mostly GI, sedation, and pancreatitis/hepatoxicity, platelet problems

Question 23

Carbamazepine and BP disorder

Answer 23

Mania

Question 24

Lamotrigine and BP disorder

Answer 24

Maintenance

Question 25

Valproate is associated with what interesting syndrome? Not first-line for what group of people?

Answer 25

Polycystic ovarian syndrome (weight gain, acne, menstrual irregularities); young women (also because of teratogenicity = neural tube defect)

Question 26

Carbamazepine is a big…What does this cause? What else is weird?

Answer 26

Inducer of p450; induces hepatic metabolism of other drugs; INHIBITS its OWN metabolism (important for dosing)

Question 27

Carbamazepine SE are similar to..Also can cause…

Answer 27

Valproate; Stevens-Johnson, blood dyscresia

Question 28

Important drug interactions for Lamotrigine and a boxed warning

Answer 28

Valproate doubles serum levels while carbamazepine reduces levels; boxed warning = rashes (can be uncomplicated or SERIOUS)

Question 29

Lamotrigine is LESS likely to be associated with…

Answer 29

Weight gain/cognitive side effects