principles of drug action 2 exam 3 bipolar

Question 1

bipolar disorders

Answer 1

It is a spectrum of affective episodes including:

• major depressive episode
• maniac episode

hypomanic

• mixed episode
• rapid cycling
• hypomanic episode

Question 2

DSM-V categories

Answer 2

Bipolar I disorder

• mania
• MDD
• 1% prevalence

Bipolar II

• hypomania
• MDD

Cyclothymia

-hypomania

0less sevre depression

-Bipolar NED

Question 3

what is Mania?

Symptoms

Answer 3

a period of elevated, expansive or irritable mood that lasts for at least 1 week

 Symptoms include
 increased energy
 goal-directed activity
 decreased need for sleep

 Elevated self-esteem
 Grandiose ideations
 Racing thoughts

 Mania may be induced by medications, including anti-depressants and psychostimulants

Question 4

what is Hypomania:

Answer 4

similar to mania although typically not as severe but must be present for at least 4 days

 Similar symptoms
 Generally does not interfere with social or occupational functioning

Question 5

 Mixed disorder

Answer 5

When criteria for both mania and major depression are met every day for at least a week

Question 6

overlapping symptoms od BP and Schiz

Answer 6

-psychosis

agression

anxiety

suicidal thoughts

mood swings

anger

impulsive

Question 7

mania and depression ( 2 mood states of BP) treatment options

Answer 7

Manic Episode- anti-psychotics (ex. Zyprexa), or benzodiazepines (sedating)

Depressive Episode- temporary co- administration with antidepressants

o Mood stabilizers are medicines that treat and prevent highs (mania) and lows (depression)

o Lithium
o Anti-epileptics

Question 8

• Mood Stabilizers

treamtment options

Answer 8

Lithium; novel agent not yet covered

• Valproic Acid (Depakote/Depakene/Depacon)-Use dependent Sodium Channel Blocker and may be involved in increasing levels of GABA; Acute mania
• Carbamazepine (Tegretol)-Use dependent Sodium Channel Blocker covered in IT-II under anti-seizure medications; acute mania
• Lamotrigene (Lamictal)- Use dependent Sodium Channel Blocker; facilitates glutamatergic transmission via Calcium channels; covered in IT-II under anti-seizure medications; maintenance therapy;
• Gabapentin (Neurontin)-Calcium channel blocker

Question 9

lithium mood stabilizer

Answer 9

Failure of “Biological Psychiatry”?
no medication has yet been designed to treat the full spectrum of bipolar disorder based on biological hypotheses of the illness

• Discovered in 1817

Utilized to treat gout

Once used in 7-up and other sodas

Used since 1949 for Bipolar; FDA approved 1970

Improvement in 50-80% of patients

• Poorer control in 20 to 30%, especially patients with: – rapid cycling

– mixed mania

– greater severity of mania

– alcohol abuse

– no family histor

Question 10

lithium MOA

Answer 10

Li+ inhibits inositol monophosphatase and interferes with the cycling of the PI pathway

• Enhancement of IP3 and calcium related signaling pathways
• Inositol depletion for signaling
• Inositol depletion in cellular membranes
• DAG signaling disruption

Lithium and other mood stabilizers: Similarities suggest common mechanism
• Valproate and its derivatives decrease intracellular inositol

concentrations through inhibition of myo-inositol-1-phosphate synthase• In cultured cell systems, carbamazepine appears to act via inositol

depletion

Question 11

lithium summary of effects

Answer 11

Question 12

lithium: monitering therapy

Answer 12

Narrow therapeutic index

 Therapeutic range: 0.6-1.2 mEq/L; Toxicity at levels >1.5

 Acute manic episodes: titrate dose to upper limit of normal (0.9-1.2 mEq/L)

 Maintenance therapy: lower therapeutic serum levels (0.6-0.9 mEq/L)

Efficacy of therapy

 1-2 weeks to become effective and reach steady-state

 High percentage of patients do not respond to therapy (>20%)

 Non-responder: no significant response after 6-12 months of continuous therapy at therapeutic drug concentrations

Question 13

lithium adverse frug reactions

Answer 13

Risk for ADRs increases with serum concentrations, but can occur with serum

concentrations within therapeutic range

 Consider reducing dose or using controlled release formulations

Somnolence

Nausea

Confusion

Diarrhea

Blunted thinking

Ataxia

Polydipsia (↑ H20 intake) and Polyuria

Tremor & muscle weakness

Myoclonus

Confusion

Nystagmus

Question 14

lithium adverse reaction

chronic events

Answer 14

Hypothyroidism-highly concentrated in the thyroid gland,

inhibits thyroid hormone release

 Nephrogenic Diabetes Insipidus-inhibits the action of ADH, causing polyuria, preventing urine concentration, and hypernatremia

 Renal Dysfunction-decrease GFR, glomerulonephritis

 Cardiac arrhythmias-bradycardia, depressed T waves

Weight gain

Question 15

lithium adverse reactions

pregnancy

Answer 15

Evidence of fetal cardiac abnormalities in humans but potential benefits may warrant use of drug

 Lamotrigene may be safer alternative

Question 16

lithium toxicity

Answer 16

Serum Concentrations
1.5-2 mEq/L: GI problems (N/V/D), CNS: lethargy, drowsiness, tremor, rigidity

 2-2.5 mEq/L: more severe GI and CNS problems plus slurred speech, blurred vision, tinnitus, ataxia, course tremor and muscle weakness

>2.5 mEq/L: seizures, stupor, coma, CV collapse, death

Question 17

lithium drug interaction: increase lithium level

Answer 17

Sodium depletion
 Excessive exercise/sweating
 Vomiting/diarrhea
 Low sodium diet/salt deficiency  Restricted dietary control

NSAIDs
 Decrease renal blood flow by inhibiting renal prostaglandin

synthesis

 Ibuprofen, naproxen and etc.  lithium level 50-60%

 No change in lithium level: ASA, sulindac

Thiazide diuretics (onset 1-2 weeks or more)
 Increase sodium excretion----\> increase lithium reabsorption

 Decreasing lithium dose by 40% may be helpful

ACEIs, ARBs —>decreases GFR —-> increase lithium level

Question 18

lihtium drug interactions decrease lithium level

Answer 18

-High Na+ diet—>increase excretion Methylxanthines; theophylline, caffeine (also

caffeine-containing beverages)

• Causes renal vasodilation —> increase GFR
• Urine alkalinizer; sodium bicarbonate

Question 19

rebound affective episodes on lithium discontinuation

Answer 19

• Lithium should never be stopped abruptly unless there are signs of toxicity
• Abrupt discontinuation of lithium prophylaxis may precipitate early recurrence of mania and depressive episodes
• Gradual discontinuation over 4 weeks may lead to a lower recurrence rate

Question 20

Mood stabilizers treatment option

Answer 20

mood-stabilizing medication to control manic or hypomanic episodes. Includes lithium, valproic acid, carbamazepine, and lamotrigine

Question 21

Antipsychotics- treatment option

Answer 21

If symptoms of depression or mania persist in spite of treatment with other medications, adding an antipsychotic drug such as olanzapine, risperidone, quetiapine, aripiprazole etc. may help alone or in combination with a mood stabilizer.

Question 22

Antidepressants- treatment option

Answer 22

Because an antidepressant can sometimes trigger a manic episode, it’s usually prescribed along with a mood stabilizer or antipsychotic

Question 23

Antidepressant-antipsychotic treatment option

Answer 23

The medication Symbyax combines the antidepressant fluoxetine and the antipsychotic olanzapine

Question 24

Anti-anxiety medications treatment option

Answer 24

Benzodiazepines may help with anxiety and improve sleep, but are usually used on a short-term basis