Antidepressants 2 Flashcards
what does lithium carbonate do ?
it prevents mood swings
tries to cut out the mania and depressive mood swings so it seems to dampen mood
it does not elevate mood
What is lithium carbonate used to treat ?
bipolar depression
it is taken prophylactically
when its taken for acute treatment what does it do ?
works in manic phase but not in the depressive phase
what is the preferred treatment in acute bipolar depression ?
antipyschotic agents instead of lithium carbonate because they are safer aand more rapid
how is lithium carbonate administered and how is it metabolised ?
given prophylactically for long periods but it still has a 3-4 week therapeutic delay and it is excreted by the kidney, 0.5 dose in 12 hours and the remainder is excreted over the next 1-2 weeks - this is too long and makes determining the appropriate dose quite difficult
why can’t other antidepressants be used in bipolar depression ?
because they make the symptoms of the disorder worse
what are the known cellular/biochemical effects caused by lithium carbonate ?
it enters through sodium (2+) channels and mimics the action of sodium ions (2+)
it is not then pumped back out of the cell by the sodium/potassium ATPase so it accumlates in the cell
this cause depolarisation of the cell affecting NA ad 5HT causing them to have an increased turnover but decreased release due to the loss of potassium ions and depolarisation of th cell
what does lithium carbonate do to the phosphatidylinositol pathway ?
it is inhibited
PI is needed to regenerate membrane PI for signal transduction
lithium depletes the membrane PI and causes intracellular inositol phoshate to build up
this inhibits the agonist induced inositol triphosphate production via these PI receptors
this reduces the ability of the cell to communicate properly
what else is affected by the lithium chloride causing a blockage of signal transduction mechanisms ?
it reduces hormone induced cAMP production - seems to reduce response to thyroid hormone however this doesnt affect the brain
what cells are more likely to be affected by lithium carbonate ?
it reflects the activity of sodium 2+ channels in different cells
- these appear to be highly expressed in the brain and kidney so will affect them more
what is the therapeutic window for lithium carbonate ?
it has a narrow therapeutic window
- 5 to 1 mmol/L plasma concentration - so plasma levels have to be monitored
- too little will have no effect but too much will be toxic
what are the toxic effects of lithium carbonate ?
RENAL AFFECT
- inhibits ADH so it causes polyuria and thirst
- causes sodium depletion and some diuretics decrease the excretion of lithium so its levels are increased
- renal damage after prolonged use therefore renal function has to be monitored
OTHER EFFECTS
- thyroid enlargment
-weight gain
- nausea, vomitting and diarrhoea
- CNS effects at high doses (3-5mmol/L) -= tremor and coma
what are atypical antidepressants ?
second gen TCAs
claimed to have less side effects
they have less side effects and lower toxicity but re not more effective or rapid
main MOA is to increase monoamines availability
e.g MIANSERIN
what does mianserin do ?
it blocks presynaptic alpha 2 receptors (autoreceptors) = this increases the release of NA as NA cannot block its own release
why can’t atypical antidepressants be given to a patient with bipolar depression ?
it would likely put the patient back into a manic state
