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Flashcards in Antidepressants 2 Deck (27):

What is lithium carbonate used to treat ?

bipolar depression
it is taken prophylactically


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


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
0.5 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 ?

- 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
- 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


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


what is bupropion ?

it is an NDRI
a NA and DA reuptake inhibitor
in US its used as an antidepressant but in the UK it is used to stop smoking


what is venlafaxine ?

it is an SNRI
serotonin and NA reuptake inhibitor


what is mirtazapine ?

it is an NAssA
NA ans specific serotonin antidepressant


what is nefazodone ?

it is an SARI
serotonin 2a antagonist/reuptake inhibitor


what is the pattern between all the new atypical antidepressants ?

they are all very similar to one another, they just have slight alterations from each other

the theme for the action of these drugs has been determined and so slight variations of drugs are being produced to work at the same mechanism so therefore there is no improvement in the treatment of depression


what are some other treatments for depression ?

electroconvulsive therapy (ECT) - 200-1500mA across the head for 0.1 to 0.6 seconds- the effects dont last forever
- administered with a light anaesthesia and neuromuscular blockade
- effective in severe depression
- side effects include confusion and memory loss possibly lasting days or weeks


what did the MRC trial of 1962 show about the effectiveness of drug therapy in depression ?

ect > tca > maoi = placebo
but later larger doses of MAOIs were shown to be effective especially in mild depression


what is the effectiveness of SSRIs like compared to other methods ?

probably less effective in severe depression compared to TCAs and MAOIs
similar effective in moderate depression
more effective when serotonin is implicated - low plasma trytophan levels can determine this


what is the % of patients which dont respond to antidepressants?

35-50% respond to placebo
30-40% fail to recover but somme patients recover without treatment - this is only depressive patients not bipolar patientss


what are the most rapid changes caused by antidepessants ?

sleep and appetite changes are changed most rapidly
the psychological symptoms take longer to be elevated


what is the evidence between TCAs and sleep in treating depression ?

combination of sleep deprivation and TCAs work better than either alone


what is SAD?

seasonal affective disorder
sometimes people become depressed in winter
serotonin is known to be involved in circadian rhtyhtms so maybe it is something to do with this