principles of drug action 2 exam 3 bipolar Flashcards
bipolar disorders
It is a spectrum of affective episodes including:
- major depressive episode
- maniac episode
hypomanic
- mixed episode
- rapid cycling
- hypomanic episode
DSM-V categories
Bipolar I disorder
- mania
- MDD
- 1% prevalence
Bipolar II
- hypomania
- MDD
Cyclothymia
-hypomania
0less sevre depression
-Bipolar NED
what is Mania?
Symptoms
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
what is Hypomania:
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
Mixed disorder
When criteria for both mania and major depression are met every day for at least a week
overlapping symptoms od BP and Schiz
-psychosis
agression
anxiety
suicidal thoughts
mood swings
anger
impulsive
mania and depression ( 2 mood states of BP) treatment options
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
• Mood Stabilizers
treamtment options
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
lithium mood stabilizer
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
lithium MOA
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
lithium summary of effects
lithium: monitering therapy
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
lithium adverse frug reactions
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
lithium adverse reaction
chronic events
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
lithium adverse reactions
pregnancy
Evidence of fetal cardiac abnormalities in humans but potential benefits may warrant use of drug
Lamotrigene may be safer alternative
lithium toxicity
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
lithium drug interaction: increase lithium level
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
lihtium drug interactions decrease lithium level
-High Na+ diet—>increase excretion Methylxanthines; theophylline, caffeine (also
caffeine-containing beverages)
- Causes renal vasodilation —> increase GFR
- Urine alkalinizer; sodium bicarbonate
rebound affective episodes on lithium discontinuation
- 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
Mood stabilizers treatment option
mood-stabilizing medication to control manic or hypomanic episodes. Includes lithium, valproic acid, carbamazepine, and lamotrigine
Antipsychotics- treatment option
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.
Antidepressants- treatment option
Because an antidepressant can sometimes trigger a manic episode, it’s usually prescribed along with a mood stabilizer or antipsychotic
Antidepressant-antipsychotic treatment option
The medication Symbyax combines the antidepressant fluoxetine and the antipsychotic olanzapine
Anti-anxiety medications treatment option
Benzodiazepines may help with anxiety and improve sleep, but are usually used on a short-term basis
