Bipolar Disorder Flashcards
What are some symptoms of manic episodes?
Talking excessively, inflated self-esteem, engagement in high-risk activities, less sleep and delusions.
What are the symptoms of a depressive episode?
It is the same criteria as for major depressive episode.
What about mixed episodes?
They constitute 40% of episodes.
Manic state with depressive symptoms or depressive state with manic symptoms. One mood state usually predominates.
What are some challenges with treating mixed episodes?
Difficult to diagnose, challenging to treat, patients experience worse symptoms and there is a higher risk of psychosis.
What is the difference between Bipolar I and Bipolar II?
Bipolar I: severe episodes, at least one MANIC episode, may have depressive episodes.
Bipolar II: At least one HYPOmanic episode, AND current or past major depressive episode.
What is the pathophysiology of mania in terms of dysregulation in neurotransmission?
Dopamine, noradrenaline and glutamate are all in excess. GABA and Acetylcholine are deficient.
What is the pathophysiology of bipolar depression in terms of dysregulation in neurotransmission?
Dopamine, noradrenaline and glutamate are all deficient
What is the pathophysiology of mania in terms of abnormal intracellular signalling system
Elevated acitvity of:
Myo-inositol
Protein Kinase C
Glycogen Synthase Kinase (GSK-3)
Myristoylated alanine-Rich C Kinase Substrate (MARCKS)
What are some treatment goals?
Resolve mood episode, prevent relapse and recurrence. Restore baseline functioning, minimize adverse effects and optimize medication adherence.
How does lithium modulate intracellular signalling?
Lithium inhibits ImPase and IPPase, which decreases myo-inositol, leading to decreased levels of mania.
Lithium also decreases MARCKS and Protein Kinase C and Glycogen Synthase Kinase, which all contributes to a decrease in mania.
How does lithium facilitate production of neuroprotective factors?
cAMP Response Element Binding Protein trascription factor is a substrate of adenylate cyclase/cAMP, promotes production of BDNF and B-cell Lymphoma.
What is the cyclical dysregulation hypothesis?
Mania - DA activity is increased, downregulation of D2 receptors, reduced DA transmission, which causes depression.
What are lithium’s pharmacokinetics?
A: almost complete 6-8hrs, peak plasma 30min- 2 hours.
D: Hydrophilic, slow intracellular entry
M/E: No metabolism 20 hour half life. Renal elimination.
What are some common adverse effects associated with lithium and possible management strategies?
Benign fine hand tremor- lower dose and add propranolol
GIT effects: Nausea and diarrhoea- lower dose. Take dose with/after food.
Polydipsia, polyuria, Diabetes Insipidus- treat with amiloride
Hypothyroidism - dont stop lithium, may add thyroid replacement therapy.
Cardiovascular effects - bradycardia, T-wave flattening/inversion, AV block.
Psychiatric effects.
What are some other late-onset adverse effects?
Reverisible, acne, folliculitis, weight gain, edema.
What is the desired and toxic therapeutic range
Maintainence dose: 0.6 - 1.0mmol/L
Toxic dose: > 1.5 mmol/L
What are some factors that increase the risk of lithium toxicity?
Low sodium levels, dehydration, being over 50, heart failure, cirrhosis, drug-drug interactions and fever.
What are some common drug-drug interactions
Diuretics, NSAIDs, ACEIs and ARBs
What are some drawbacks to using lithium?
Narrow therapeutic range, risk of congenital cardiac anomalies, intolerable adverse effect profile, lag in antidepressant effect.
What is the proposed mood stabilizing mechanism of anti-epileptics?
Valproic acid: depletes inositol levels. Inhibits GSK-3 activity
Carbamazepine: depletes inositol levels, increases BDNF, inhibits cAMP and G proteins
Lamotrigine: inhibits glutamate activity, increases GABA release.
What are the indications and efficacy of valproic acid?
Acute manic episodes: similar efficacy to Li and olanzapine
Mixed episodes and rapid cycling, more effective than Li+.
What are the indications of lamotrigine?
Depression and mood stabilizing.
What is the most common adverse effect?
Rash, greatest risk within first 6 weeks
What happens when we add valproic acid to lamotrigine
The dose of lamotrigine decreases by 50%.
What happens when we add lamotrigine to valproic acid?
Reduce the starting dose by 50% of lamotrigine.
