Mood Disorder Pharmacology Flashcards
(44 cards)
In general, how is unipolar depression different from bipolar disorder?
unipolar depression is characterized by episodes of depression, separated by periods of euthymia
bipolar disorder is characterized by episodes of depression (briefer) followed by episodes of mania
What is the prevalence of depression?
1 in 10 patients seen in primary care!
it’s the 4th most common compaint
***Note that 70% of medical care over-utilizers have at some time in their lives had a diagnosis of major depression
What hypothesis is the make idea fo neurochemical basis of affective disorders?
the amine hypothesis
Describe the amine hypothesis for affective disorers.
certain levels of amine NTs and receptor sensitivity are necessary for normal mood
(NE, 5HT, DA)
Depression occurs if receptors are insensitive or if amine synthesis, storage, or release is deficient
Mania occurs if there is an excess of NT or a receptor hypersensitivity
What ist he major issue with the amine hypothesis of mood disorders?
there’s a mismatch between the time course of treatment:
neurochemical effects can occur in 1-2 days, while clinical improvement takes 10-21 days
What are the two general drug classes for treatment of mood disorders?
antidepressants
mood stabilizers
What percentage of patients do not respond to initial antidepressant therapy?
30-40%!
What effects do tricyclic antidepressants cause in normal, non-depressed, subjects?
NO stimulation of mood elevating effect
you get antimuscarinic effects: dry mouth, blurred vision, constipation, urinary retention, sleepiness and light headedness
What is the effect of TCAs in depressed subjects?
elevation of mood only after 2-3 weeks
50% experience dry mouth and tachycardia
What is the mechanism of the TCAs
block the reuptake of NE and/or 5HT by nerve terminals
some are NE selective and others are NE/5HT mixed action
This results in higher concentration of the NTs at their receptors
What are the adverse effects of the TCAs
orthostatic hypotension
antimuscarini effects (especialy in elderly patients): acute confusional state, constipation, glaucoma
weight gain
tachycardia and increased tendency for arrhythmias with high doses
What are some drug interactions you’ll see with the tricyclic antidepressants?
- they’ll potentiate central depressants like alcohol, sedatives, and opioids
- the antimuscarinic effects may delay gastric emptying time, so you get increased inactivation of levodopa in treating parkinsonism
What do MAOIs do?
they irreversibly block the oxidative deamination of monoamines like NE and 5HT
What’s the difference between MAOa and MAOb?
MAOa metabolizes NE and 5HT in the brain and gut
MAOb metabolizes DA in the blood platelets
How long do you have to wait for changes to be seen with MAOIs?
the NTs change in 24-48 hours, but it takes 3+ weeks for clinical effect
Why are MAOIs used more for treating symptomatically?
the therapeutic index is very low - only 5!
usually hospitalize 1 week too
What is the major concen for drug interaction with the MAOIs?
They will potentiate sympathomimetic amins
especially indirect acting amines like tyramine
tyramine is usually metabolized by hepatic MAO, but ifyou take an MAOI, tyramine will build up and enter systemic circulation
it enhances release of catecholamines from peripheral and central nerve terminals and the adrenal medulla
this results in massive adrenergic stimulation that can cause a hypertensive crisis
What option is available in Europe to lower the incidence of interaction with tyramine?
they have approved selective and reversible MAOa inhibitors called Brofaramine and maclobemide
they don’t inhibit all the MAO, so you don’t get the interaction
What are some major examples of SSRIs?
fluoxetine = prozac
sertraline = zoloft
citalopram = celexa
escitalopram = lexapro
What are the adverse effects of SSRIs and how are they different from the TCAs and MAOIs?
nausea, diarrhea, weight LOSS, sexual dysfunction
stimulation - anxiety, nervousness, insomnia
They are unusual in that they’re NOT sedating
What is the black box marning for fluoxetine?
they can increase suicidal thinking in children, adolescence and young adults
Which serotonin receptor probably contributes to the clinical improvement seen with SSRIs?
5-HT 2a
What is the difference between an autoreceptor and a heteroreceptor?
autoreceptors are acted on by 5HT to inhibit the addition release of 5HT
Heteroreceptors are acted on by NE to inhibit the release of 5-HT
What are hte 4 major atypical antidepressants?
velafaxine (effexor)
duloxetine (cymbalta)
Mirtazapine (Remeron)
Buproprion (wellbutrin)
